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M.3.1.4.5 (Add two 3-digit numbers with single regrouping)
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Introduction to Free Fall A free-falling object is an object that is falling under the sole influence of gravity. Any object that is being acted upon only by the force of gravity is said to be in a state of free fall. There are two important motion characteristics that are true of free-falling objects: âą Free-falling objects do not encounter air resistance. âą All free-falling objects (on Earth) accelerate downwards at a rate of 9.8 m/s/s (often approximated as 10 m/s/s for back-of-the-envelope calculations) Because free-falling objects are accelerating downwards at a rate of 9.8 m/s/s, a ticker tape trace or dot diagram of its motion would depict an acceleration. The dot diagram at the right depicts the acceleration of a free-falling object. The position of the object at regular time intervals - say, every 0.1 second - is shown. The fact that the distance that the object travels every interval of time is increasing is a sure sign that the ball is speeding up as it falls downward. Recall from an earlier lesson, that if an object travels downward and speeds up, then its acceleration is downward. Free-fall acceleration is often witnessed in a physics classroom by means of an ever-popular strobe light demonstration. The room is darkened and a jug full of water is connected by a tube to a medicine dropper. The dropper drips water and the strobe illuminate the falling droplets at a regular rate - say once every 0.2 seconds. Instead of seeing a stream of water free-falling from the medicine dropper, several consecutive drops with increasing separation distance are seen. The pattern of drops resembles the dot diagram shown in the graphic at the right. The Acceleration of Gravity It was learned in the previous part of this lesson that a free-falling object is an object that is falling under the sole influence of gravity. A free-falling object has an acceleration of 9.8 m/s/s, downward (on Earth). This numerical value for the acceleration of a free-falling object is such an important value that it is given a special name. It is known as the acceleration of gravity - the acceleration for any object moving under the sole influence of gravity. A matter of fact, this quantity known as the acceleration of gravity is such an important quantity that physicists have a special symbol to denote it - the symbol g. The numerical value for the acceleration of gravity is most accurately known as 9.8 m/s2. There are slight variations in this numerical value (to the second decimal place) that are dependent primarily upon on altitude. We will occasionally use the approximated value of 10 m/s2 in order to reduce the complexity of the many mathematical tasks that we will perform with this number. By so doing, we will be able to better focus on the conceptual nature of physics without too much of a sacrifice in numerical accuracy. g = 9.8 m/s2, downward Look It Up! Even on the surface of the Earth, there are local variations in the value of the acceleration of gravity (g). These variations are due to latitude, altitude and the local geological structure of the region. Recall from an earlier lesson that acceleration is the rate at which an object changes its velocity. It is the ratio of velocity change to time between any two points in an object's path. To accelerate at 9.8 m/s2 means to change the velocity by 9.8 m/s each second. If the velocity and time for a free-falling object being dropped from a position of rest were tabulated, then one would note the following pattern. Time (s) Velocity (m/s) 0 0 1 - 9.8 2 - 19.6 3 - 29.4 4 - 39.2 5 - 49.0 . Observe that the velocity-time data above reveal that the object's velocity is changing by 9.8 m/s each consecutive second. That is, the free-falling object has an acceleration of approximately 9.8 m/s2. Another way to represent this acceleration of 9.8 m/s2 is to add numbers to our dot diagram that we saw earlier in this lesson. The velocity of the ball is seen to increase as depicted in the diagram at the right. (NOTE: The diagram is not drawn to scale - in two seconds, the object would drop considerably further than the distance from shoulder to toes.) Representing Free Fall by Graphs âą Early in Lesson 1 it was mentioned that there are a variety of means of describing the motion of objects. One such means of describing the motion of objects is through the use of graphs - position versus time and velocity vs. time graphs. In this part of Lesson 5, the motion of a free-falling motion will be represented using these two basic types of graphs. Representing Free Fall by Position-Time Graphs A position versus time graph for a free-falling object is shown below. Observe that the line on the graph curves. As learned earlier, a curved line on a position versus time graph signifies an accelerated motion. Since a free-falling object is undergoing an acceleration (g = 9.8 m/s/s), it would be expected that its position-time graph would be curved. A further look at the position-time graph reveals that the object starts with a small velocity (slow) and finishes with a large velocity (fast). Since the slope of any position vs. time graph is the velocity of the object (as learned in Lesson 3), the small initial slope indicates a small initial velocity and the large final slope indicates a large final velocity. Finally, the negative slope of the line indicates a negative (i.e., downward) velocity. Representing Free Fall by Velocity-Time Graphs A velocity versus time graph for a free-falling object is shown below. Observe that the line on the graph is a straight, diagonal line. As learned earlier, a diagonal line on a velocity versus time graph signifies an accelerated motion. Since a free-falling object is undergoing an acceleration (g = 9,8 m/s/s, downward), it would be expected that its velocity-time graph would be diagonal. A further look at the velocity-time graph reveals that the object starts with a zero velocity (as read from the graph) and finishes with a large, negative velocity; that is, the object is moving in the negative direction and speeding up. An object that is moving in the negative direction and speeding up is said to have a negative acceleration (if necessary, review the vector nature of acceleration). Since the slope of any velocity versus time graph is the acceleration of the object (as learned in Lesson 4), the constant, negative slope indicates a constant, negative acceleration. This analysis of the slope on the graph is consistent with the motion of a free-falling object - an object moving with a constant acceleration of 9.8 m/s/s in the downward direction. The Kinematic Equations The goal of this first unit has been to investigate the variety of means by which the motion of objects can be described. The variety of representations that we have investigated includes verbal representations, pictorial representations, numerical representations, and graphical representations (position-time graphs and velocity-time graphs). In Lesson 6, we will investigate the use of equations to describe and represent the motion of objects. These equations are known as kinematic equations. There are a variety of quantities associated with the motion of objects - displacement (and distance), velocity (and speed), acceleration, and time. Knowledge of each of these quantities provides descriptive information about an object's motion. For example, if a car is known to move with a constant velocity of 22.0 m/s, North for 12.0 seconds for a northward displacement of 264 meters, then the motion of the car is fully described. And if a second car is known to accelerate from a rest position with an eastward acceleration of 3.0 m/s2 for a time of 8.0 seconds, providing a final velocity of 24 m/s, East and an eastward displacement of 96 meters, then the motion of this car is fully described. These two statements provide a complete description of the motion of an object. However, such completeness is not always known. It is often the case that only a few parameters of an object's motion are known, while the rest are unknown. For example as you approach the stoplight, you might know that your car has a velocity of 22 m/s, East and is capable of a skidding acceleration of 8.0 m/s2, West. However you do not know the displacement that your car would experience if you were to slam on your brakes and skid to a stop; and you do not know the time required to skid to a stop. In such an instance as this, the unknown parameters can be determined using physics principles and mathematical equations (the kinematic equations). The BIG 4 The kinematic equations are a set of four equations that can be utilized to predict unknown information about an object's motion if other information is known. The equations can be utilized for any motion that can be described as being either a constant velocity motion (an acceleration of 0 m/s/s) or a constant acceleration motion. They can never be used over any time period during which the acceleration is changing. Each of the kinematic equations include four variables. If the values of three of the four variables are known, then the value of the fourth variable can be calculated. In this manner, the kinematic equations provide a useful means of predicting information about an object's motion if other information is known. For example, if the acceleration value and the initial and final velocity values of a skidding car is known, then the displacement of the car and the time can be predicted using the kinematic equations. Lesson 6 of this unit will focus upon the use of the kinematic equations to predict the numerical values of unknown quantities for an object's motion. The four kinematic equations that describe an object's motion are: There are a variety of symbols used in the above equations. Each symbol has its own specific meaning. The symbol d stands for the displacement of the object. The symbol t stands for the time for which the object moved. The symbol a stands for the acceleration of the object. And the symbol v stands for the velocity of the object; a subscript of i after the v (as in vi) indicates that the velocity value is the initial velocity value and a subscript of f (as in vf) indicates that the velocity value is the final velocity value. Each of these four equations appropriately describes the mathematical relationship between the parameters of an object's motion. As such, they can be used to predict unknown information about an object's motion if other information is known. In the next part of Lesson 6 we will investigate the process of doing this. Kinematic Equations and Problem-Solving The four kinematic equations that describe the mathematical relationship between the parameters that describe an object's motion were introduced in the previous part of Lesson 6. The four kinematic equations are: In the above equations, the symbol d stands for the displacement of the object. The symbol t stands for the time for which the object moved. The symbol a stand for the acceleration of the object. And the symbol v stands for the instantaneous velocity of the object; a subscript of i after the v (as in vi) indicates that the velocity value is the initial velocity value and a subscript of f (as in vf) indicates that the velocity value is the final velocity value. Problem-Solving Strategy In this part of Lesson 6 we will investigate the process of using the equations to determine unknown information about an object's motion. The process involves the use of a problem-solving strategy that will be used throughout the course. The strategy involves the following steps: 1. Construct an informative diagram of the physical situation. 2. Identify and list the given information in variable form. 3. Identify and list the unknown information in variable form. 4. Identify and list the equation that will be used to determine unknown information from known information. 5. Substitute known values into the equation and use appropriate algebraic steps to solve for the unknown information. 6. Check your answer to ensure that it is reasonable and mathematically correct. The use of this problem-solving strategy in the solution of the following problem is modeled in Examples A and B below. Example Problem A . Ima Hurryin is approaching a stoplight moving with a velocity of +30.0 m/s. The light turns yellow, and Ima applies the brakes and skids to a stop. If Ima's acceleration is -8.00 m/s2, then determine the displacement of the car during the skidding process. (Note that the direction of the velocity and the acceleration vectors are denoted by a + and a - sign.) The solution to this problem begins by the construction of an informative diagram of the physical situation. This is shown below. The second step involves the identification and listing of known information in variable form. Note that the vf value can be inferred to be 0 m/s since Ima's car comes to a stop. The initial velocity (vi) of the car is +30.0 m/s since this is the velocity at the beginning of the motion (the skidding motion). And the acceleration (a) of the car is given as - 8.00 m/s2. (Always pay careful attention to the + and - signs for the given quantities.) The next step of the strategy involves the listing of the unknown (or desired) information in variable form. In this case, the problem requests information about the displacement of the car. So d is the unknown quantity. The results of the first three steps are shown in the table below. Diagram: Given: Find: vi = +30.0 m/s vf = 0 m/s a = - 8.00 m/s2 d = ?? The next step of the strategy involves identifying a kinematic equation that would allow you to determine the unknown quantity. There are four kinematic equations to choose from. In general, you will always choose the equation that contains the three known and the one unknown variable. In this specific case, the three known variables and the one unknown variable are vf, vi, a, and d. Thus, you will look for an equation that has these four variables listed in it. An inspection of the four equations above reveals that the equation on the top right contains all four variables. vf2 = vi2 + 2 âą a âą d Once the equation is identified and written down, the next step of the strategy involves substituting known values into the equation and using proper algebraic steps to solve for the unknown information. This step is shown below. (0 m/s)2 = (30.0 m/s)2 + 2 âą (-8.00 m/s2) âą d 0 m2/s2 = 900 m2/s2 + (-16.0 m/s2) âą d (16.0 m/s2) âą d = 900 m2/s2 - 0 m2/s2 (16.0 m/s2)*d = 900 m2/s2 d = (900 m2/s2)/ (16.0 m/s2) d = (900 m2/s2)/ (16.0 m/s2) d = 56.3 m The solution above reveals that the car will skid a distance of 56.3 meters. (Note that this value is rounded to the third digit.) The last step of the problem-solving strategy involves checking the answer to assure that it is both reasonable and accurate. The value seems reasonable enough. It takes a car a considerable distance to skid from 30.0 m/s (approximately 65 mi/hr) to a stop. The calculated distance is approximately one-half a football field, making this a very reasonable skidding distance. Checking for accuracy involves substituting the calculated value back into the equation for displacement and insuring that the left side of the equation is equal to the right side of the equation. Indeed it is! Example Problem B Ben Rushin is waiting at a stoplight. When it finally turns green, Ben accelerated from rest at a rate of a 6.00 m/s2 for a time of 4.10 seconds. Determine the displacement of Ben's car during this time period. Once more, the solution to this problem begins by the construction of an informative diagram of the physical situation. This is shown below. The second step of the strategy involves the identification and listing of known information in variable form. Note that the vi value can be inferred to be 0 m/s since Ben's car is initially at rest. The acceleration (a) of the car is 6.00 m/s2. And the time (t) is given as 4.10 s. The next step of the strategy involves the listing of the unknown (or desired) information in variable form. In this case, the problem requests information about the displacement of the car. So d is the unknown information. The results of the first three steps are shown in the table below. Diagram: Given: Find: vi = 0 m/s t = 4.10 s a = 6.00 m/s2 d = ?? The next step of the strategy involves identifying a kinematic equation that would allow you to determine the unknown quantity. There are four kinematic equations to choose from. Again, you will always search for an equation that contains the three known variables and the one unknown variable. In this specific case, the three known variables and the one unknown variable are t, vi, a, and d. An inspection of the four equations above reveals that the equation on the top left contains all four variables. d = vi âą t + Âœ âą a âą t2 Once the equation is identified and written down, the next step of the strategy involves substituting known values into the equation and using proper algebraic steps to solve for the unknown information. This step is shown below. d = (0 m/s) âą (4.1 s) + Âœ âą (6.00 m/s2) âą (4.10 s)2 d = (0 m) + Âœ âą (6.00 m/s2) âą (16.81 s2) d = 0 m + 50.43 m d = 50.4 m The solution above reveals that the car will travel a distance of 50.4 meters. (Note that this value is rounded to the third digit.) The last step of the problem-solving strategy involves checking the answer to assure that it is both reasonable and accurate. The value seems reasonable enough. A car with an acceleration of 6.00 m/s/s will reach a speed of approximately 24 m/s (approximately 50 mi/hr) in 4.10 s. The distance over which such a car would be displaced during this time period would be approximately one-half a football field, making this a very reasonable distance. Checking for accuracy involves substituting the calculated value back into the equation for displacement and insuring that the left side of the equation is equal to the right side of the equation. Indeed, it is! The two example problems above illustrate how the kinematic equations can be combined with a simple problem-solving strategy to predict unknown motion parameters for a moving object. Provided that three motion parameters are known, any of the remaining values can be determined. In the next part of Lesson 6, we will see how this strategy can be applied to free fall situations. Or if interested, you can try some practice problems and check your answer against the given solutions. Kinematic Equations and Free Fall As mentioned in Lesson 5, a free-falling object is an object that is falling under the sole influence of gravity. That is to say that any object that is moving and being acted upon only be the force of gravity is said to be "in a state of free fall." Such an object will experience a downward acceleration of 9.8 m/s/s. Whether the object is falling downward or rising upward towards its peak, if it is under the sole influence of gravity, then its acceleration value is 9.8 m/s/s. Like any moving object, the motion of an object in free fall can be described by four kinematic equations. The kinematic equations that describe any object's motion are: The symbols in the above equation have a specific meaning: the symbol d stands for the displacement; the symbol t stands for the time; the symbol a stands for the acceleration of the object; the symbol vi stands for the initial velocity value; and the symbol vf stands for the final velocity. Applying Free Fall Concepts to Problem-Solving There are a few conceptual characteristics of free fall motion that will be of value when using the equations to analyze free fall motion. These concepts are described as follows: âą An object in free fall experiences an acceleration of -9.8 m/s/s. (The - sign indicates a downward acceleration.) Whether explicitly stated or not, the value of the acceleration in the kinematic equations is -9.8 m/s/s for any freely falling object. âą If an object is merely dropped (as opposed to being thrown) from an elevated height, then the initial velocity of the object is 0 m/s. âą If an object is projected upwards in a perfectly vertical direction, then it will slow down as it rises upward. The instant at which it reaches the peak of its trajectory, its velocity is 0 m/s. This value can be used as one of the motion parameters in the kinematic equations; for example, the final velocity (vf) after traveling to the peak would be assigned a value of 0 m/s. âą If an object is projected upwards in a perfectly vertical direction, then the velocity at which it is projected is equal in magnitude and opposite in sign to the velocity that it has when it returns to the same height. That is, a ball projected vertically with an upward velocity of +30 m/s will have a downward velocity of -30 m/s when it returns to the same height. These four principles and the four kinematic equations can be combined to solve problems involving the motion of free-falling objects. The two examples below illustrate application of free fall principles to kinematic problem-solving. In each example, the problem solving strategy that was introduced earlier in this lesson will be utilized. Example Problem A Luke Autbeloe drops a pile of roof shingles from the top of a roof located 8.52 meters above the ground. Determine the time required for the shingles to reach the ground. The solution to this problem begins by the construction of an informative diagram of the physical situation. This is shown below. The second step involves the identification and listing of known information in variable form. You might note that in the statement of the problem, there is only one piece of numerical information explicitly stated: 8.52 meters. The displacement (d) of the shingles is -8.52 m. (The - sign indicates that the displacement is downward). The remaining information must be extracted from the problem statement based upon your understanding of the above principles. For example, the vi value can be inferred to be 0 m/s since the shingles are dropped (released from rest; see note above). And the acceleration (a) of the shingles can be inferred to be -9.8 m/s2 since the shingles are free-falling (see note above). (Always pay careful attention to the + and - signs for the given quantities.) The next step of the solution involves the listing of the unknown (or desired) information in variable form. In this case, the problem requests information about the time of fall. So t is the unknown quantity. The results of the first three steps are shown in the table below. Diagram: Given: Find: vi = 0.0 m/s d = -8.52 m a = - 9.8 m/s2 t = ?? The next step involves identifying a kinematic equation that allows you to determine the unknown quantity. There are four kinematic equations to choose from. In general, you will always choose the equation that contains the three known and the one unknown variable. In this specific case, the three known variables and the one unknown variable are d, vi, a, and t. Thus, you will look for an equation that has these four variables listed in it. An inspection of the four equations above reveals that the equation on the top left contains all four variables. d = vi âą t + Âœ âą a âą t2 Once the equation is identified and written down, the next step involves substituting known values into the equation and using proper algebraic steps to solve for the unknown information. This step is shown below. -8.52 m = (0 m/s) âą (t) + Âœ âą (-9.8 m/s2) âą (t)2 -8.52 m = (0 m) *(t) + (-4.9 m/s2) âą (t)2 -8.52 m = (-4.9 m/s2) âą (t)2 (-8.52 m)/(-4.9 m/s2) = t2 1.739 s2 = t2 t = 1.32 s The solution above reveals that the shingles will fall for a time of 1.32 seconds before hitting the ground. (Note that this value is rounded to the third digit.) The last step of the problem-solving strategy involves checking the answer to assure that it is both reasonable and accurate. The value seems reasonable enough. The shingles are falling a distance of approximately 10 yards (1 meter is pretty close to 1 yard); it seems that an answer between 1 and 2 seconds would be highly reasonable. The calculated time easily falls within this range of reasonability. Checking for accuracy involves substituting the calculated value back into the equation for time and insuring that the left side of the equation is equal to the right side of the equation. Indeed it is! Example Problem B Rex Things throws his mother's crystal vase vertically upwards with an initial velocity of 26.2 m/s. Determine the height to which the vase will rise above its initial height. Once more, the solution to this problem begins by the construction of an informative diagram of the physical situation. This is shown below. The second step involves the identification and listing of known information in variable form. You might note that in the statement of the problem, there is only one piece of numerical information explicitly stated: 26.2 m/s. The initial velocity (vi) of the vase is +26.2 m/s. (The + sign indicates that the initial velocity is an upwards velocity). The remaining information must be extracted from the problem statement based upon your understanding of the above principles. Note that the vf value can be inferred to be 0 m/s since the final state of the vase is the peak of its trajectory (see note above). The acceleration (a) of the vase is -9.8 m/s2 (see note above). The next step involves the listing of the unknown (or desired) information in variable form. In this case, the problem requests information about the displacement of the vase (the height to which it rises above its starting height). So d is the unknown information. The results of the first three steps are shown in the table below. Diagram: Given: Find: vi = 26.2 m/s vf = 0 m/s a = -9.8 m/s2 d = ?? The next step involves identifying a kinematic equation that would allow you to determine the unknown quantity. There are four kinematic equations to choose from. Again, you will always search for an equation that contains the three known variables and the one unknown variable. In this specific case, the three known variables and the one unknown variable are vi, vf, a, and d. An inspection of the four equations above reveals that the equation on the top right contains all four variables. vf2 = vi2 + 2 âą a âą d Once the equation is identified and written down, the next step involves substituting known values into the equation and using proper algebraic steps to solve for the unknown information. This step is shown below. (0 m/s)2 = (26.2 m/s)2 + 2 âą(-9.8m/s2) âąd 0 m2/s2 = 686.44 m2/s2 + (-19.6 m/s2) âąd (-19.6 m/s2) âą d = 0 m2/s2 -686.44 m2/s2 (-19.6 m/s2) âą d = -686.44 m2/s2 d = (-686.44 m2/s2)/ (-19.6 m/s2) d = 35.0 m The solution above reveals that the vase will travel upwards for a displacement of 35.0 meters before reaching its peak. (Note that this value is rounded to the third digit.) The last step of the problem-solving strategy involves checking the answer to assure that it is both reasonable and accurate. The value seems reasonable enough. The vase is thrown with a speed of approximately 50 mi/hr (merely approximate 1 m/s to be equivalent to 2 mi/hr). Such a throw will never make it further than one football field in height (approximately 100 m), yet will surely make it past the 10-yard line (approximately 10 meters). The calculated answer certainly falls within this range of reasonability. Checking for accuracy involves substituting the calculated value back into the equation for displacement and insuring that the left side of the equation is equal to the right side of the equation. Indeed, it is! Kinematic equations provide a useful means of determining the value of an unknown motion parameter if three motion parameters are known. In the case of a free-fall motion, the acceleration is often known. And in many cases, another motion parameter can be inferred through a solid knowledge of some basic kinematic principles. [t comes from the GREEK name "Epilepsia" which means "taking hold of or seizing". - It is a disorder characterized by: recurrent seizures. SEIZURES R ectment transient attacks of: R epresent: R esult from: ASSOCIATED WITH: somatic, psychic, or, autonomic clinical featmes. clinical features of abnormally hyperexcitable cortical neurons. paroxvsmal and excessive electrical neuronal discharges. EEG changes & may be disturbance of consciousness. same causes of convulsions 1. Idiopathic epile~ âą It is the commonest cause. no cause can be detected ( 65 % ) âą It may be associated with positive family history in some cases. âą It starts in the l st & 2nd decades in the form of: -- Grand ma! epilepsy. Petit mal epilepsy. Myoclonic epilepsy. Atonic seizures. 2. Secondary epilepsy A. Local causes in the brain: l. Congenital: 2. Traumatic: cerebral palsy. a cause can be detected cerebral contusion or laceration. 3. Inflammatory: 4. Neoplastic: 5. Degenerative: 6. Vascular: encephalitis, brain tumours. mening1t1s, presenile dementia. brain abscess. stroke (especially hemon-hagic), hypertensive encephalopathy. B. General causes with secondary effects on the brain: I. Toxic: 2. Iatrogenic: 3. Metabolic: 4. Endocrinal: 5. Organ failure: 6. Heart disease: 7. Nutritional: - Alcohol, cocaine, lead. - Lidocaine, INH. - j glucose & ! glucose. - Hypoparathyroidism. - Hepatic failme. - Adam's Stoke's attacks. - Pellagra. - Botulism, tetanus. - Ambilhar, Amphetamine, Aminophylline. - j Ca & ! Ca. - Hype1thyroid crisis. - Renal failure. - Fallot's tetralogy. - j Na & ! Na. - Vitamin B6 deficiency. 8. Physical: 9. HYSTERICAL. - High fevers. - Heat stroke. 136 137 CLINICAL PICTURE 1. GENERALISED SEIZURES " Excessive electrical discharges from cortical neurons in BOTH hemispheres simultaneously " I. II. 1. Grand Mal Epile~: 1. Pre-ictal stage "attacks of tonic-clonic convulsions " (aura) It is a warning sign of a coming attack. It may be: âą Somatic: âą Psychic: âą Autonomic: 2. Ictal stage Myoclonus, Hallucinations. Tachycardia, (seizure) Sudden loss of consciousness: Parasthesias. Sweating. for seconds to minutes. -- Tonic phase (few seconds) o The UL & LL: o o o o The HEAD: The JAWS: CYANOSIS: are extended. is retracted to one side & the eye balls rolled up. are firmly clenched, with biting of the TONGUE. due to impaired respiration. There may be incontinence of urine. Clonic phase (few minutes) o The UL & LL: o The HEAD: 3. Post-ictal stage - It may be: âą Somatic: âą Psychic: âą Autonomic: Drug of choice: contract & relax repeatedly & rapidly. jerks forcibly. (sequelae) Todd's paralysis(< 24 hours, due to neuronal exhaustion). Confusion. Vomiting. Carbamazepine (Tegretol) or Phenytoin (Epanutin) Petit Mal Epilepsy: "attacks of loss of consciousness " " Absence " It starts in childhood & improves at puberty & usually disappears at the age of 20. 2. It is NOT PRECEEDED by aura & NOT FOLLOWED by sequelae. 3. It is usually PRECIPITATED by: hyperventilation 4. It is characterized by: or photic stimulation. sudden loss of consciousness of short duration (few seconds). 5. It may be associated with: âą High frequency ( 50 attacks / day). âą Falling to the ground without warning. âą Jerky movements of the head & UL Drug of choice: (myoclonic petit mal). Valproate (Depakine) or Succinimide (Zarontin) 137 138 Ill. M oclonic Seizures: "attacks of involuntary clonic movements " - It is characterized by: sudden, jerky, shock-like INVOLUNTARY muscle contraction. âą The jerks are bilateral contractions, mainly of the shoulders and arms. âą However, some patients repmtjerking in the lower limbs, trunk, or head. - It may be of 2 types: - Occurs singly âą Simple: âą As a pait of: I Drug of choice: IV. Atonic seizures: (no loss of consciousness). - Grand mal epilepsy (aura). - Petit mal epilepsy. Valproate (Depakine) or Clonazepam (Rivotril) I - Transient attacks of brief loss of postural tone, often resulting in falls and injuries. 2. PARTIAL SEIZURES "Excessive electrical discharges from cmtical neurons in a ce1tain area in ONE hemisphere" A. Simple seizures: " No disturbance in consciousness " - The CP depends on the site of the hyperexcitable neurones in the cerebral cortex, whether in: "Motor area or Senso,y areas". 1. Motor fits: âą Focal fits: âą Motor jacksonian fits: 2. General Sensory fits: âą Focal fits: âą Sensory jacksonian fits: 3. Special Senso1y fits: âą Visual hallucinations: âą Auditory hallucinations: âą Olfactory hallucinations: B. Complex seizures: - SITE: movement of part of a limb or the whole limb. movement of one side of the body (see before). parasthesia of part of a limb or the whole limb. parasthesia of one side of the body (see before). irritation of the visual sensory area. irritation of the auditory sensory area. initation of the uncus. " disturbance in consciousness " The hyperexcitable neurons are in the Temporal lobe "Temporal lobe epilepsy". - DURATION: The seizure lasts few seconds to few minutes. - The seizure starts with A ura, followed by A bsence, Automatism, Amnesia: 1. 2. 3. 4. A ura: A bsence: Automatism: A mnesia: Olfactory hallucinations, Deja-vu phenomenon, Sensation of fear. Absent patient with staring eyes (with no response to conversation). Involuntary Purposeless acts: motor ( eg, lip smacking, chewing) or verbal. No recalling of the seizure. 138 139 3. PARTIAL SEIZURES ~ GENERALISED SEIZURES " Partial seizures may spread to involve the whole brain .- secondarily generalised seizures " . HY-sterical epilepsY âą Usually: âą The cause: âą Incidence: young neurotic Sj2 . psychological & there is no organic lesion. usually occurs in the presence of people. âą It is associated with: âą EEG: âą It is not associated with: normal. âą Missed ttt. âą Menses. âą Alkalosis. anxiety, palpitaion & hyperventilation. tongue biting or incontinence of urine. âą Alcohol use & Drug abuse ( e.g. cocaine ). âą S timulation by photons & Hyperventilation. âą S leep deprivation & Stress & sudden withdrawal of antiepileptic drngs. INVESTIGATIONS 1. EEG: âą It is the most specific test for epilepsy because it records the electrical activity of the brain. âą It shows specific pattern: 2. LOCAL INVESTIGATIONS: "Epilepsy waves". "CT & MRI of the brain" âą To identify or exclude a LOCAL CAUSE of seizures in the brain. 3. GENERAL INVESTIGATIONS: "Laboratory investigations" âą To search for a GENERAL CAUSE of seizures, e.g. blood glucose. 139 140 TREATMENT A. General Measures: 1. 2. Moderation of the patient's physical activity. A void the precipitating factors ( Alcohol, hyperventilation, photic stimulation ...... ). 3. A ketogenic diet is encouraged because it will induce acidosis: - Acidosis is beneficial as it raises the threshold of stimulation of the brain cells. B. Specific Treatment: 2. 1. Treatment of the cause in secondary epilepsy. Anti-epileptic drugs: a) Always sta1t with one drug, then add another drug if there is no response. b) Always stop the drugs ONLY if: âą The patient stays free of symptoms for at least 2 years. âą The patient has a normal EEG. 3. Side effects of Anti-epileptic drugs: I . Skin rash. 2. 3. Bone marrow depression. Ataxia. Drug 1. Barbiturates (Pbenonobarbitone) 2. Hydantoin (Epanutin) 3. Carbamazepine 4. Clonazepam 5. Valproate 6. Succinamide ANTI-EPILEPTIC DRUGS NEW ANTI-EPILEPTIC DRUGS - These drugs are new dtugs that may be used in resistant seizures. 1. Lamotrigine: 200 - 400 mg/ day. 2. Felbamate: 3. Gabapentin: 400- 800 mg/ day. 600 - 1200 mg/ day. \ " General rules for use ": Dose 100-600 mg I day 100-600 mg / day 200-600 mg I day 2-6 mg I day 500-1500 mg I day 500-1000 mg / day Best indicated - Broad spectrum. - Not for petit mal. - Grand mal. - Motor Jacksonian fits. - Grand mal. - Motor Jacksonian fits. - Complex seizures. - Not for petit ma!. - Myoclonic. - Grand mat. - Broad spectrum. - Petit mat. 140 141 STATUS EPILEPTICUS DEFINITION - A medical emergency: 1. Repeated attacks of generalized convulsions, with lack of recove,y of consciousness, 2. Persistent attack of seizure lasting for at least 30 minutes. OR, - If the convulsions are not stopped rapidly, coma deepens & death may occur due to: heart failure or respiratory failure or brain damage or hyperpyrexia. - The most common causes are: sudden withdrawal of anti-epileptic drugs & stroke. TREATMENT A. General Measures: l. Take care of: " ABC " âą Place the patient on the ground, to guard against falling from bed. âą Mouth gag & 02 inhalation ( endo-tracheal intubation may be needed). âą Record the vital signs regularly. 2. Take a sample of: - Venous blood: for the level of: - A.tierial blood: for the level of: 3. a nti-epileptic drugs, a lcohol. pH, p0 2, pC02, HC0 3. Give cerebral dehydrating measures: e.g. Frusemide, cone. Mannitol, Dexamethazone. B. Specific Treatment: - Phenytoin with diazepam (or clonazepam) immediately: 1. Phenytoin: 2. Diazepam: Clonazepam: seizures recur: 15 mg I Kg slow infusion. 5 mg slowly IV, to be repeated after 5 minutes if seizures recur: maximum dose: 20 mg. OR: 2 mg slowly IV, to be repeated after 5 minutes if maximum dose: 6 mg. - If seizures persist after 20 min. of Phenytoin & diazepam: 3. PHENOBARBITONE: - In resistant cases: 200 mg infusion. 4. GENERAL ANAESTHESIA: may be used.Generate all of these 25 questions Part A: Each correct answer is worth 5. 1. The regular pentagon shown has a side length of 2 cm. The perimeter of the pentagon is (A) 2 cm (B) 4 cm (C) 6 cm (D) 8 cm (E) 10 cm 2 cm 2. The faces of a cube are labelled with 1, 2, 3, 4, 5, and 6 dots. Three of the faces are shown. What is the total number of dots on the other three faces? (A) 6 (B) 8 (C) 10 (D) 12 (E) 15 3. The equation that best represents \a number increased by _ve equals 15" is (A) n ô 5 = 15 (B) n _ 5 = 15 (C) n + 5 = 15 (D) n + 15 = 5 (E) n _ 5 = 15 4. The line graph shows the number of bobbleheads sold at a store each year. The sale of bobbleheads increased the most between (A) 2016 and 2017 (B) 2017 and 2018 (C) 2018 and 2019 (D) 2019 and 2020 (E) 2020 and 2021 Number of 2016 2017 2018 2019 2020 Year Sale of Bobbleheads 2021 Bobbleheads 20 40 60 80 5. Starting at 72, Aryana counts down by 11s: 72; 61; 50; : : : . What is the last number greater than 0 that Aryana will count? (A) 4 (B) 5 (C) 6 (D) 7 (E) 8 6. In the diagram, \ABC = 90_. The value of x is (A) 68 (B) 23 (C) 56 (D) 28 (E) 26 Day of the Week 44° x° A B C x° 7. Which of the following values is closest to zero? (A) ô1 (B) 5 4 (C) 12 (D) ô4 5 (E) 0:9 Grade 8 8. A jar contains 267 quarters. One quarter is worth $0.25. How many quarters must be added to the jar so that the total value of the quarters is $100.00? (A) 33 (B) 53 (C) 103 (D) 133 (E) 153 9. A package of 8 greeting cards comes with 10 envelopes. Kirra has 7 cards but no envelopes. What is the smallest number of packages that Kirra needs to buy to have more envelopes than cards? (A) 3 (B) 4 (C) 5 (D) 6 (E) 7 10. For the points in the diagram, which statement is true? (A) e > c (B) b < d (C) f > b (D) a < e (E) a > c y x (e, f ) (a, b) (c, d ) Part B: Each correct answer is worth 6. 11. The 26 letters of the English alphabet are listed in an in_nite, repeating loop: ABCDEFGHIJKLMNOPQRSTUVWXY ZABC : : : What is the 258th letter in this sequence? (A) V (B) W (C) X (D) Y (E) Z 12. A public holiday is always celebrated on the third Wednesday of a certain month. In that month, the holiday cannot occur on which of the following days? (A) 16th (B) 22nd (C) 18th (D) 19th (E) 21st 13. A circular spinner is divided into three sections. An arrow is attached to the centre of the spinner. The arrow is spun once. The probability that the arrow stops on the largest section is 50%. The probability it stops on the next largest section is 1 in 3. The probability it stops on the smallest section is (A) 1 4 (B) 2 5 (C) 1 6 (D) 2 7 (E) 3 10 14. A positive number is divisible by both 3 and 4. The tens digit is greater than the ones digit. How many positive two-digit numbers have this property? (A) 4 (B) 5 (C) 6 (D) 7 (E) 8 15. A rectangular pool measures 20 m by 8 m. There is a 1 m wide walkway around the outside of the pool, as shown by the shaded region. The area of the walkway is (A) 56 m2 (B) 60 m2 (C) 29 m2 (D) 52 m2 (E) 50 m2 20 m 8 m 1 m Grade 8 16. The results of asking 50 students if they participate in music or sports are shown in the Venn diagram. What percentage of the 50 students do not participate in music and do not participate in sports? (A) 0% (B) 80% (C) 20% (D) 70% (E) 40% Music Sports 15 5 20 17. There are 2 3 as many golf balls in Bin F as in Bin G. If there are a total of 150 golf balls, how many fewer golf balls are in Bin F than in Bin G? (A) 15 (B) 30 (C) 50 (D) 60 (E) 90 18. In the sequence shown, Figure 1 is formed using 7 squares. Each _gure after Figure 1 has 5 more squares than the previous _gure. What _gure has 2022 squares? (A) Figure 400 (B) Figure 402 (C) Figure 404 (D) Figure 406 (E) Figure 408 Figure 1 Figure 2 Figure 3 19. Mateo's 300 km trip from Edmonton to Calgary passed through Red Deer. Mateo started in Edmonton at 7 a.m. and drove until stopping for a 40 minute break in Red Deer. Mateo arrived in Calgary at 11 a.m. Not including the break, what was his average speed for the trip? (A) 83 km/h (B) 94 km/h (C) 90 km/h (D) 95 km/h (E) 64 km/h 20. Equilateral triangle ABC has sides of length 4. The midpoint of BC is D, and the midpoint of AD is E. The value of EC2 is (A) 7 (B) 6 (C) 6:25 (D) 8 (E) 10 Part C: Each correct answer is worth 8. 21. The positive factors of 6 are 1, 2, 3, and 6. There are two perfect squares less than 100 that have exactly _ve positive factors. What is the sum of these two perfect squares? (A) 177 (B) 80 (C) 145 (D) 52 (E) 97 22. In the list p; q; r; s; t; u; v, each letter represents a positive integer. The sum of the values of each group of three consecutive letters in the list is 35. If q + u = 15, then p + q + r + s + t + u + v is (A) 85 (B) 70 (C) 80 (D) 90 (E) 75 Grade 8 23. The net shown is folded to form a cube. An ant walks from face to face on the cube, visiting each face exactly once. For example, ABCFED and ABCEFD are two possible orders of faces the ant visits. If the ant starts at A, how many possible orders are there? (A) 24 (B) 48 (C) 32 (D) 30 (E) 40 A D B C E F 24. The number 385 is an example of a three-digit number for which one of the digits is the sum of the other two digits. How many numbers between 100 and 999 have this property? (A) 144 (B) 126 (C) 108 (D) 234 (E) 64 25. Student A, Student B, and Student C have been hired to help scientists develop a new avour of juice. There are 4200 samples to test. Each sample either contains blueberry or does not. Each student is asked to taste each sample and report whether or not they think it contains blueberry. Student A reports correctly on exactly 90% of the samples containing blueberry and reports correctly on exactly 88% of the samples that do not contain blueberry. The results for all three students are shown below. Student A Student B Student C Percentage correct on samples 90% 98% (2m)% containing blueberry Percentage correct on samples 88% 86% (4m)% not containing blueberry Student B reports 315 more samples as containing blueberry than Student A. For some positive integers m, the total number of samples that the three students report as containing blueberry is equal to a multiple of 5 between 8000 and 9000. The sum of all such values of m is (A) 45 (B) 36 (C) 24 (D) 27 (E) 29Riferimenti normativi per il settore residenziale: Art 81: Accesso alla rete viariaâ>> il cancello deve essere arretrato di almeno 4,5m dal filo esterno del marciapiede Art 82: Passo carrabileâ>> larghezza non inferiore a 4,5m e non superiore a 6,5m Art 83:Pendenza Rampa â>> max 16% Art 97: Superficie minima degli ambienti - cucina â>> min 5mq - studioâ>> min 7mq - soggiornoâ>> min 14 mq - soggiorno spazi di cotturaâ>> 17 -camera (1posto letto)â>> 8mq - camera (2posti letto)â>> 12mq Superficie alloggio totale â>> non inferiore a 28 mq Art 95: Altezze minime- cucina, soggiorno, camera e studioâ>> min 2,70m -locali accessoriâ>> min 2,40 m (bagno, lavanderie) - locali di servizioâ>> min 2,10m (disimpegni, riposti.) - soppalchiâ>> min 2,10m - parapettiâ>> non inf. a 1,1m (10 cm cordolo) (92) Art 86: Distanze - negli edifici di nuova costruzione la distanza degli edifici dal confine con proprietĂ di terzi â nei NAFâ>> non inf. a 3 m â altri ambiti â>> non inf. a 5m Art 89: Scale (R.E. ) âalzateâ>> max 12 consecutive â a chiocciolaâ>> consentite solo allâinterno di unâunitĂ abit. â illuminazioneâ>> se collegano piĂč di due piani devono . essere areati con lucernario. Dim: 0,3 mq . per ogni piano servito (R.I.: 0,4 mq x piano) â areazione â>> non ci puĂČ essere areazione verso i vani scala . ( Lo dice anche il regolamento dâigiene ) (R.I) â>> superficie non inferiore a 1mq per piano servi. â larghezza (R.I.) â>> deve garantire la possibilitĂ di soccorso e . trasporto di persone Art 88: Locali sotterranei â>> non possono MAI essere adibiti ad abitazione Locali seminterratiâ>> possono ma devono rispettare determinati . requisiti - lâaltezza media deve essere > di 2,7m Art 91: Coperturaâ>> istallazione di apparati tecnici non deve essere visibile . dalle pubbliche vie Art 98: Bagni â>> ambiente contenente il vaso deve essere disimpegnato . dalla cucina (R.I: disimpegnato dai locali abitabili, esclusione Secondo bagno se Ăš a servizio esclusivo di una camera) (R.I)â>> deve essere dotato di vaso, lavabo, bidet doccia o vasca â>> il lavabo puĂČ essere ubicato nellâantibagno Art 100: Areazione â>> riscontro dâaria deve essere garantito su aperture . perpendicolari o contrapposte.(non inf. a 1\10) â>> appartamenti inf. a 60mq possono essere . monoaffaccio ( ma non esposti a nord) Art 125: Raccolta rifiuti (R.E)â>> non meno di 0,18mq per ogni abitante . virtuale â>> non meno di 5 mq â>> altezza minima 2,4m (R.I: 2 m) â>> deve avere un punto di allacciamento dâacqua Regolamento dâigiene â>> dimensione tale da poter contenere 4,5l Di rifiuti per abitante.( in ogni caso > di 2mq) â>> scarichi sifonati dallâacqua di lavaggio â>> accorgimenti che assicurino unâadeguata Difesa antimurina e antinsetti Norma UNI 10750: superficie commerciale (ciĂČ che compriamo) , cioĂš la somma delle superfici coperteâ>> 100% delle superfici calpestatili â>>100% delle superfici su cui poggiano . Le pareti divisorie interne non portanti â>> 50% delle pareti portanti interne perimetrali â>> 25% delle aree non abitabili Superfici scoperteâ>> 25% dei balconi e delle terrazze scoperte â>> 35% dei balconi e dei terrazzi coperti (3 lati) â>> 35% dei pati e dei porticati â>> 60% delle verande â>> 15% dei giardini di appartamento â>> 10% dei giardini di ville e villini (Se un muro Ăš al confine con un altro appartamento lo considero dalla mezzeria, se confina con uno spazio comune idem, lo considero tutto invece se da sullâesterno ) Regolamento dâigiene (su esso prevale il Re) : norme che discipilinano degli aspetti della vita quotidiana al fine di tutelare la salute dei fruitori Si occupa di : Rumori , odori , fumi, vapori. Scarichi nel sottosuolo Pulizia e decoro Malattie infettive IgenicitĂ degli ambienti Pareti trasparenti (tenendo conto di telai e infissi)â>> deve avere un area pari a 1\8 (nazionale), 1\10 (Milano ) della superficie di pavimento ProfonditĂ di pavimentoâ>> non deve superare i 2,5m dalla finestra Bagno cieco solo se la superficie lorda di pavimento Ăš inferiore ai 70mq e se Ăš presente una sola camera da letto , oppure se Ăš un secondo bagno (altrimenti finestra > 0,5 apribile). Superficie illuminanteâ>> superficie totale dellâapertura meno - superficie finale non utile (C): 60 cm - superficie superiore non utile (A) A= va considerato per intero se non ci sono aggetti o se questi sono inferiori a 150 cm. Al contrario ne considero solo un terzo. Es: con aggetto, b+ 1\3a . Se il rapporto illuminante Ăš rispettato la profonditĂ del locale non puĂČ essere piĂč di 2,5 volte lâaltezza del voltino . Se non Ăš rispettato (inferiore a 1\8) allora deve essere 3,5 volte Alloggi devono essere dotatiâ per 1\2 peroneâ>> 1 spazio cottura,1 servizio igienico , 1 ripostiglio â per 3\4 personeâ>> 1 cucina indipendente, 1 servizio igienico , 1 ripostiglio â per 4\5 persone â>> 1 cucina indipendente, 2 servizi igienici, 1 ripostiglio (per il secondo servizio Ăš richiesta una superficie minima di 2mq e un lato minimo di 1,2m) Dotazione dei servizi: Cucinaâ>> pavimenti e pareti con superficie Di materiale impermeabile, liscio, lavabile,resist. â>> soffitto materiale traspirante â>> cappa collegata a ogni punto di cottura (Vedi bagno su) Prevenzione incendi : definisce âdimensionamentiâaccessi allâarea (locali di intrattenimento e di pubblico Spettacolo â>> larghezza 3,5 â>> h libera 4m â>> raggio di svolta 13m â>> pendenza non sup al 10% â>> resist al carico almeno 20t âprofonditĂ locali â>> i locali al chiuso non possono Essere ubicati oltre il secondo piano Interrato (non oltre i 10m) . Questi se Sono tra i 7,5 e i 10 m devono essere Protetti da unâimpianto sprinkler e Essere dotati di uscite sicure. â carichi dâincendio â comunicazione (locali di intrattenimento e di pubb. Spettacolo â>> locali possono comunicare con altre AttivitĂ purchĂ© dotate di filtri a prova di Fumo e di porte REI (ameno 30) (queste Non vanno cont nel comp. delle vie dâuscit) â compartimentazioni â autorimesse â comportamento al fuoco Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty DesirĂ©e Nieuwenhuis | NatĂ lia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. The majority of the studies examining boys with obesity indicate an early onset of puberty, while not all reported an earlier onset of puberty. In detail, high leptin, TNF-α, and IL-6 levels combined with low adiponectin levels stimulate the activation of the HPG axis in girls and boys with obesity, and 5, 45, 50, 51 REFERENCES 1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. May- o Clin Proc. 2017;92(2):251-265. 2. Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty? The Lancet Child & adolescent health. 2019;3(1):44-54. 3. WorldHealthOrganization. Facts and figures on childhood obesity. 2017. 4. Guglielmi V, Sbraccia P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord. 2018; 23(1):3-14. 5. Gomez-Hernandez A, Beneit N, Diaz-Castroverde S. Escribano O. 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FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including âonset of puberty and adiposity/obesityâ, âonset of pubertyâ, âchildren with obesityâ, âadipose tissueâ, âchildhood obesityâ, âadiposityâ, âobesityâ, âadipokine(s)â, âHPG axisâ, âadipokines ovary/ova- riesâ, or âadipokines testesâ, either alone or in combination. 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Associations between body mass, leptin, IGF-I and circulating adrenal androgens in children with obesity and premature adrenarche. Eur J Endocrinol. 2002;146(4):537-543. 56. Böttner A, Jr K, MĂŒller G, et al. Gender Differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metabol. 2004;89(8):4053- 4061. 57. Unanue N, Bazaes R, Iñiguez G, Cortes F, Avila A, Mericq V. Adre- narche in Prader-Willi syndrome appears not related to insulin sensi- tivity and serum adiponectin. Horm Res. 2007;67(3):152-158. 58. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and repro- ductive axis: a narrative review. Metabolism: clinical and experimental. 2013;62(4):457-478. 59. Machinal-Quelin F, Dieudonne MN, Pecquery R, Leneveu MC, Giudicelli Y. Direct in vitro effects of androgens and estrogens on ob gene expression and leptin secretion in human adipose tissue. Endo- crine. 2002;18(2):179-184. 60. Dobrzyn K, Smolinska N, Kiezun M. Adiponectin: A new regulator of female reproductive system. Int J Endocrinol. 2018;2018:1-12, 7965071. 61. Martin LJ. Implications of adiponectin in linking metabolism to testic- ular function. Endocrine. 2014;46(1):16-28. 62. Mathew H, Castracane VD, Mantzoros C. Adipose tissue and repro- ductive health. Metabolism: clinical and experimental. 2018;86:18-32. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 10 of 10 NIEUWENHUIS ET AL. 63. Sitticharoon C, Sukharomana M, Likitmaskul S, Churintaraphan M, Maikaew P. Corrigendum to: Increased high molecular weight adiponectin, but decreased total adiponectin and kisspeptin, in central precocious puberty compared with aged-matched prepubertal girls. Reprod Fertil Dev. 2017;29:2506-2517. 64. Das UN. Is obesity an inflammatory condition? Nutrition. 2001; 17(11-12):953-966. 65. Comninos AN, Jayasena CN, Dhillo WS. The relationship between gut and adipose hormones, and reproduction. Hum Reprod Update. 2014; 20(2):153-174. 66. Singh A, Choubey M, Bora P, Krishna A. Adiponectin and chemerin: contrary adipokines in regulating reproduction and metabolic disor- ders. Reproductive sciences (Thousand Oaks, Calif). 2018;25:1462- 1473. 67. Tsatsanis C, Dermitzaki E, Avgoustinaki P, Malliaraki N, Mytaras V, Margioris AN. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis. Hormones (Athens). 2015; 14:549-562. 68. Kang MJ, Oh YJ, Shim YS, Baek JW, Yang S. Hwang IT. The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty. 2018;34:627-630. 69. Lee J, Song J, Hootman JM, et al. Obesity and other modifiable fac- tors for physical inactivity measured by accelerometer in adults with knee osteoarthritis: data from the osteoarthritis initiative (OAI). Arthritis Care Res (Hoboken). 2012;53-61. 70. Bramswig J, Dubbers A. Disorders of pubertal development. Deutsches Arzteblatt international. 2009;106:295-303. quiz 04 71. Elias CF, Purohit D. Leptin signaling and circuits in puberty and fertil- ity. Cell Mol Life Sci. 2013;70(5):841-862. 72. Riumallo J, Durnin JV. Changes in body composition in adolescent boys. Eur J Clin Nutr. 1988;42(2):107-112. 73. Siervogel RM, Demerath EW, Schubert C, et al. Puberty and body composition. Horm Res. 2003;60(Suppl 1):36-45. 74. Zhang J. Gong M. Andrologia: Review of the role of leptin in the regu- lation of male reproductive function; 2018. 75. Kauffman AS, Gottsch ML, Roa J, et al. Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology. 2007;148(4): 1774-1783. 76. Zeydabadi Nejad S, Ramezani Tehrani F, Zadeh-Vakili A. The role of kisspeptin in female reproduction. Int J Endocrinol Metab. 2017;15:1- 11, e44337. 77. Sorensen K, Aksglaede L, Petersen JH, Juul A. Recent changes in pubertal timing in healthy Danish boys: associations with body mass index. J Clin Endocrinol Metab. 2010;95(1):263-270. 78. Juul A, Magnusdottir S, Scheike T, Prytz S, Skakkebaek NE. Age at voice break in Danish boys: effects of pre-pubertal body mass index and secular trend. Int J Androl. 2007;30(6):537-542. 79. Lee JM, Wasserman R, Kaciroti N, et al. Timing of puberty in overweight versus obese boys. Pediatrics. 2016;137(2):137-146, e20150164. 80. He F, Guan P, Liu Q, Crabtree D, Peng L, Wang H. The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study. BMC Pub- lic Health. 2017;17:664-673. 81. Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Expres- sion of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia. 2007;39(1):22-27. 82. Martins AD, Moreira AC, Sa R, et al. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta. 1852;2015: 1824-1832. 83. Morash BA, Willkinson D, Ur E, Wilkinson M. Resistin expression and regulation in mouse pituitary. FEBS Lett. 2002;526(1-3):26-30. 84. Cabrera SM, Bright GM, Frane JW, Blethen SL, Lee PA. Age of thelarche and menarche in contemporary US females: a cross- sectional analysis. Journal of pediatric endocrinology & metabolism: JPEM. 2014;27(1-2):47-51. 85. Herman-Giddens ME, Steffes J, Harris D, et al. Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings Network. Pediatrics. 2012;130(5):e1058-e1068. 86. WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1-452. 87. Akin I, Tolg R, Hochadel M, et al. No evidence of âobesity paradoxâ after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry. JACC Cardiovasc Interv. 2012;5(2): 162-169. 88. Marcovecchio ML, Chiarelli F. Obesity and growth during childhood and puberty. World Rev Nutr Diet. 2013;106:135-141. How to cite this article: Nieuwenhuis D, Pujol-Gualdo N, Arnoldussen IAC, Kiliaan AJ. Adipokines: A gear shift in puberty. Obesity Reviews. 2020;21:e13005. https://doi.org/ 10.1111/obr.13005 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are goverSe il rapporto illuminante Ăš rispettato la profonditĂ del locale non puĂČ essere piĂč di 2,5 volte lâaltezza del voltino . Se non Ăš rispettato (inferiore a 1\8) allora deve essere 3,5 volte Alloggi devono essere dotatiâ per 1\2 peroneâ>> 1 spazio cottura,1 servizio igienico , 1 ripostiglio â per 3\4 personeâ>> 1 cucina indipendente, 1 servizio igienico , 1 ripostiglio â per 4\5 persone â>> 1 cucina indipendente, 2 servizi igienici, 1 ripostiglio (per il secondo servizio Ăš richiesta una superficie minima di 2mq e un lato minimo di 1,2m) Dotazione dei servizi: Cucinaâ>> pavimenti e pareti con superficie Di materiale impermeabile, liscio, lavabile,resist. â>> soffitto materiale traspirante â>> cappa collegata a ogni punto di cottura (Vedi bagno su) Prevenzione incendi : definisce âdimensionamentiâaccessi allâarea (locali di intrattenimento e di pubblico Spettacolo â>> larghezza 3,5 â>> h libera 4m â>> raggio di svolta 13m â>> pendenza non sup al 10% â>> resist al carico almeno 20t âprofonditĂ locali â>> i locali al chiuso non possono Essere ubicati oltre il secondo piano Interrato (non oltre i 10m) . Questi se Sono tra i 7,5 e i 10 m devono essere Protetti da unâimpianto sprinkler e Essere dotati di uscite sicure. â carichi dâincendio â comunicazione (locali di intrattenimento e di pubb. Spettacolo â>> locali possono comunicare con altre AttivitĂ purchĂ© dotate di filtri a prova di Fumo e di porte REI (ameno 30) (queste Non vanno cont nel comp. delle vie dâuscit) â compartimentazioni â autorimesse â comportamento al fuocoNutrition Notes Nutrition- study of how your body uses food Process by which body uses nutrients How you look and feel Resist diseases and illness How you perform physically and mentally Nutrients: substances in food your body needs to grow, repair and supply energy to your body cells 6 Classes of Nutrients 1.Carbohydrates: 1 gram= 4 calories 2. Protein: 1 gram- 4 calories 3. Fats: 1 gram= 9 calories 4.Water 5. Vitamins 6. Minerals Calorie: measurement of energy in food Metabolism: Rate at which body burns energy(calories) Hunger: physical drive to eat Appetite: pshycological desire for food What influences your food choices: Foods you like Health Reasons Family and Culture Time & Money Advertising Emotions Friends Social Media: Modeling Nutrients Carbohydrates: your bodyâs main source of energy sugars/starches in food 45%-65% of diet #1 source of energy Simple: sugars converted to glucose= energy (fruits, dairy, honey, some manufactured foods) Complex: sugars linked together (starches) (grains, bread, pasta, beans, vegetables) Fiber: tough, indigestible carbohydrates Cleans our digestive system Prevents some types of cancer Prevents heart disease (fruits, vegetables, whole grains,nuts) 2. Protein: growth and repair of body tissues Made up of chemicals called âamino acidsâ Basic building material of all body cells (muscles, bones, skin, internal organs) Secondary source of energy protein(hemoglobin) attaches to oxygen in blood Functions as hormones regulating body functions 10-15% of diet *Body uses 20 Amino Acids found in food ( body produces 11 and 9 must come from diet) Essential amino acids: 9 amino acids body doesn't produce Complete Amino Acids: foods that contain all 9 essential amino acids ( animal products) Incomplete Amino Acids: food products that do not contain all 9 essential amino acids. Fats 15-25% of diet Secondary source of energy Blood clotting Controlling inflammation Maintains healthy skin/hair absorb /transport fat soluble vitamins Regulates body temperature Types of Fat Unsaturated: âgoodâ fat Liquid at room temperature Can help fight heart disease (veg oil, nuts) Saturated: âbadâ fat Solid at room temp Clogs arteries Causes strokes, heart attack, diabetes (animal products, meat, dairy) Cholesterol: waxy like fat substance found in meat products HDL: good type of cholesterol Body creates(liver) Creates cell wall, hormones, and vit D LDL: bad cholesterol- found in foods (clogs arteries) 4. Trans Fat: âone of the worst type of fatsâ Formed by a process called âhydrogenationâ: adding Hydrogen molecules to unsaturated fats to make it more solid and resistant to chemical change. Vitamins A vitamin is a chemical compound that is needed in small amounts for the human body to work correctly. Vitamins are classified as either fat soluble (vitamins A, D, E and K) or water soluble (vitamins B and C). This difference between the two groups is very important. It determines how each vitamin acts within the body. The fat soluble vitamins are soluble in lipids (fats). Fat soluble vitamins can be stored in our body Water soluble vitamins must be taken every day Human body produces some amounts of Vitamin D & KMake mcq quiz with 4 option in which one is correct -'10 Basis of Material Science âą .....;;;";;;"~~;;,,;;,,,,;.;.,,;;,,,;,,;.;,.,------------ 6. Temporary materials: Some materials are meant to be placed in the oral cavity for a short period of time for different reasons. âą Temporary crowns: While a permanent crown is prepared in the dental laboratory, the patient must wait for few days before it can be fabricated and cemented into place. Does patient experience any problems during this time period? If the tooth is vital (the pulp is alive), the patient is likely to experience pain and sensitivity while eating and drinking, also it looks unesthetic. What can be done to solve this problem? A temporary crown is placed before the patient leaves the clinic. It is constructed and luted in the same appointment in which the crown preparation is done. Temporary crowns are not very strong or esthetic but they serve adequately till the permanent crown is ready to be cemented. âą Temporary restorations: Sometimes it is difficult to decide immediately the best line of treatment for a particular tooth. The exact condition of the pulp may not be obvious to the dentist from the patient's symptoms. A dentist removes all or part of the decay and then places a temporary restoration to have time to observe the behaviour of the pulp or to give the pilip time to heal before deciding the further treatment required. Classification based on Location of Fabrication 4,9 Materials can be classified based on the location of fabrication into: âą Direct restorative materials. âą Indirect restorative materials Direct restorative materials: They include those materials which are used to restore cavity preparations directly in the oral cavity (Box 1.5). Box 1.5: Examples of direct restorative materials Amalgam, composites, glass ionomer and other materials, which set by chemical reactions in the mouth. Indirect restorative materials: It includes those restorations which must be fabricated outside the mouth, indirectly on a cast/ model/ die, because their processing condition would harm oral tissues. Materials used in the construction of such prosthesis are called indirect restorative materials (Box 1.6). Box 1.6: Examples of indirect restorative materials Gold inlays, crowns of metal, ceramic and polymers, which are processed at elevated temperatures. Some indirect composite restorations can be processed under specific wavelength of light, e.g. Ceramage. Classification based on Longevity of Use 1. Permanent restorations: These restorations are not planned to be replaced for a particular time period. Though they are referred to as permanent, actually they are not, e.g. fillings, crowns, bridges and dentures do not last forever (Fig. 1.5). 2. Temporary restorations: These restorations are planned to be replaced in a short period of time, such as few days to weeks. For ~ Permanent C/) c c -.2 0 c- :;::; Cll co Interim ~ Q; 0 .8ll::1iJ C/) o~ Cll a:: c:=:J Temporary Time period Fig. 1.5: Diagram depicting the time period of use of a restoration. (Arrow in permanent restoration depicts that such restorations are not planned to be replaced for a long period of time.) Introducton to Dental Materials Dental materials Box 1.7: Characteristics of metals 1. High thermal and electrical conductivity 2. Ductility (pure metals are very soft and they can be bent without breaking) 3. Opacity (they do not transmit light) 4. Luster (they have a surface that strongly reflects light and appears bright and shiny) 5. They tend to dissolve to some extent in water or other aqueous solutions, producing cations. 6. All metals are white (actually gray) except for gold, which is yellow, and copper, which is reddish. 7. All metals are solid at room temperature except mercury, which is liquid at room temperature and is used with silver alloys as amalgam. 8. All metals have high melting temperatures because of high strength of the metallic bond that holds the atoms together. 3. Polymers 4. Composites Composites are mixtures of two or more of the first three classes in which the different components remain distinct from one another in the final structure. A common example is composite resin. Fig. 1.7a: Three-dimensional structure of iron (metal) Metals Metals are the oldest of the three classes of materials that have been used as dental materials. Metals are characterized by metallic bonds (Box 1.7) which will be discussed in the next chapter. Metals solidify with their atoms in a regular or crystalline arrangement (see Chapter 2), often in the form of a cube (Fig. 1.7a). example, temporary fillings done in a tooth during root canal treatment, which have to be replaced within 2-4 days during subsequent visits. They are used to protect the tooth and provide function till the final restoration is done. 3. Interim restoration: At times, dental treatment requires "long-term" definite temporary restorations or "interim" restorations. For examle, a 7-year-old child, met with trauma and fractured one of his central incisors. A large composite build- up may serve his immediate requirement until the root formation is completed and a permanent crown is placed. 5 Classification based on the Chemical Nature of the Material These are the atoms that make up a material and the way they are bonded together determine the properties of that materiaLS Weak bonds make for weak materials and vice versa (Table 1.4). Materials can be classified into different categories based on their primary atomic bonds (Fig. 1.6): 1. Metals 2. Ceramics Fig. 1.6: Classification of dental materials based on chemical nature 12 Basis of Material Science Box 1.9: Benefits of ceramics in dentistry 1. Many ceramic oxides are used as pigmenting agents. These oxides produce good range of colors. Due to this characteristic, we are able to match almost any tooth color with good esthetic results. 2. They are inert, i.e. not chemically reactive. This quality provides ceramics with good bio- compatibility. 3. Ceramic materials are translucent, like natural teeth. This translucency gives the ceramic crown a more natural appearance than any other dental material. Fig. 1.7b: Internal arrangement of tetrahedral structure of ceramic (silica) four large oxygen atoms surround smaller silicon atom Ceramics A ceramic is a compound formed by the union of a metallic and a non-metallic element (Box 1.8). Most of these materials are oxides, formed by the union of oxygen with metals such as silicon, aluminum, calcium and magnesium (Fig.1.7b). Ceramics may be simple or complex. Examples of simple ceramics are alumina and silica. Examples of complex ceramics are feldspar (potassium aluminum silicate) and kaolin (hydrated aluminum silicate). Ceramics may be crystalline or non- crystalline (i.e. amorphous). Porcelain is a specific type of ceramic used extensively in dentistry (Box 1.9). Box 1.8: Characteristics of ceramics 1. High melting points. 2. Brittleness, which means they cannot be bent or deformed (no sliding) to any extent without actually cracking and breaking. 3. They are poor conductor of heat and electricity. 4. They are chemically inert. 5. They have excellent esthetic result in terms of matching natural teeth. Fig. 1.8: Stucture of synthetic polymer Polymers They are the latest addition (early to mid- 1900s) to dental materials. Most of the polymers are nowadays synthesized by humans. Polymers are giant, long-chain organic molecules (Fig. 1.8). Polymers are characterized by covalent bonds within each molecule, giving them tremendous strength in a single direction. Try to break a nylon rope by pulling it! They are poor conductors of heat and electri- city. Most polymers have a structure containing thousands of carbon atoms linked together like beads on a string. Others, such as silicone polymers are formed with silicon-oxygen bonds. Introducton to Dental Materials Table 1.4: Characteristics of different materials 13 Characteristics Bond Properties Crystal structure Metals Metallic bonding High strength and hardness, high electrical and thermal conductivity BCC, FCC, or HCP unit cells Ceramics Ionic or covalent bonding, or both High hardness and stiffness, electrically insulating, refractory, and chemically inert Crystalline or amorphous Polymers Covalent bonding Low sensitivity, high electrical resistivity, and low thermal conductivity, strength and stiffness vary widely Amorphous and crystalline Composites Composites are combinations of any of the basic ceramic, metallic and polymeric materials (Box 1.10). Each material that makes up composites is called a phase. Their properties tend to be somewhere between those of their basic constituents and are used to enhance their performance, longevity and handling chracterstics. Box 1.10: Types of composites in dentistry 1. Ceramic - metallic composite: Tungsten carbide bur. 2. Metal - polymer composite: Die materials in dental laboratory. 3. Ceramic - polymer composite: Enamel, dentin, bone and restorative composites. A composite is a kind of "combination" of materials, which compliment each other. The properties lacking in one material are compensated by those of the other material. For example, restorative composite has two phases, namely resin and fillers. Teeth and bones are examples of natural composites. Enamel is a composite of hydroxyapatite (which is a ceramic material) and protein (which is a polymer). EVALUATION OF DENTAL MATERIALS Most manufacturers of dental materials maintain a quality assurance programme (As per international standard like ADA specifications) and materials are thoroughly tested before being released into the market for dental practitioner (Fig. 1.9). Laboratory Evaluations Most ADA/ ANSI specifications involve laboratory tests. The tests performed as per these specifications are useful but they all are performed in vitro, (carried out in the laboratory away from the clinical conditions) which have a lot of limitations in clinical practice.lO Clinical Notes 1. For example, most of the direct restorative materials are tested for their compressive strength but ultimately the material is subjected to a combination of compressive, tensile and shear stresses, which may decide the final success or failure of the material under masticatory load. 2. Similarly upper dentures mostly fracture along the midline because of bending. Hence a bending or transverse strength ~B-a-s-is-o-f-M-a-t-e-ria-I-S~c-ie-n-c-e-------------- ---------. test is far more meaningful for denture base materials than a compression test. Clinical Trials The majority of new materials are subjected to extensive clinical trials normally in co-operation with a dental college or hospital departments prior to their release. CONCLUSION As the number of available materials is going up, it is important that the dentist remains more aware about new products so that their judgement about the selection of material remains successful. Materials which have not been thoroughly evaluated should be avoided, specially with clinical dentistry falling under Consumer Protection Act (CPA). I Research and development I iI Manufacturer/analysis Ideal requirements for clinical use: Thermal, optical, mechanical, chemical, biological Available materials and their properties are evaluated Launch of new I product Choice and selection of material by the dentist Critical assessment based on clinical performance I I H feedback to I