What was the result of the first human gene transfer study in 1990 involving TIL genetically marked with a retrovirus vector?

Understand whether infused TIL tracked back to tumors

Why do many still resist the advancements in gene editing?

There are risks involved in the process.

What possible errors can come from gene editing, aside from off-target cleavage?

Unknown variables due to unfamiliarity.

Decreased potential for mutations

Increased accuracy of targeting

Which gene therapy article described the possibility and potential of gene therapy for correcting hereditary diseases?

Patient death during a trial of therapy using genes, 1999

Foundational Proposal and Rationale for Gene Therapy, 1972

Premature and Non-approved attempt at a clinical Gene Therapy, 1980

What was the first clinical trial of genome editing focused on?

Gene editing of persons who have HIV

Why do many still resist gene editing advancements?

There are no potential benefits

Who wrote the 'Foundational Proposal and Rationale for Gene Therapy' in 1972?

Theodore Friedmann and Richard Roblin

THE RISK OF GENE EDITING

Understanding the Features of Finance: A Guide for Newbies Finance is a broad field that involves managing money, including activities such as investing, borrowing, lending, budgeting, saving, and forecasting. As a beginner, understanding the basic features of finance is crucial. This guide will relate these features to blockchain technology, cryptocurrency, and decentralized finance (DeFi). 1. Basic Financial Concepts Investing: Putting money into assets like stocks, bonds, or real estate with the expectation of earning a return. In the blockchain world, this translates to investing in cryptocurrencies like Bitcoin, Ethereum, or various DeFi projects. Borrowing and Lending: Traditional finance involves banks and financial institutions providing loans. In the DeFi space, platforms like Aave and Compound allow users to borrow and lend cryptocurrencies without intermediaries. Budgeting: Planning how to allocate your income to cover expenses, save, and invest. Using blockchain technology, you can utilize smart contracts to automate budgeting and savings processes. 2. Blockchain Technology Blockchain is a decentralized ledger that records transactions across multiple computers. It is the technology behind cryptocurrencies and has several key features: Transparency: All transactions are recorded on a public ledger, making them visible to anyone. Security: Cryptographic techniques ensure that data on the blockchain is secure and tamper-proof. Decentralization: No single entity controls the blockchain, reducing the risk of centralized control and failure. 3. Cryptocurrencies Cryptocurrencies are digital or virtual currencies that use cryptography for security. They operate on blockchain technology and offer several advantages: Lower Transaction Costs: Sending money across borders is cheaper with cryptocurrencies compared to traditional banking methods. Accessibility: Anyone with an internet connection can access cryptocurrencies, promoting financial inclusion. Ownership and Control: Users have complete control over their funds without relying on banks. 4. Decentralized Finance (DeFi) DeFi is a movement that uses blockchain technology to recreate and improve traditional financial systems in a decentralized manner. Key features of DeFi include: Smart Contracts: Self-executing contracts with the terms directly written into code, enabling trustless and automated transactions. Liquidity Pools: Users can provide their assets to a pool and earn interest or rewards, promoting liquidity in the DeFi ecosystem. Yield Farming: A strategy where users move their assets between different DeFi platforms to maximize returns. 5. Applications in DeFi and Blockchain HaloFi Save: A platform that leverages blockchain technology to help people save money efficiently and securely. It encourages users to save larger amounts for longer durations, offering higher interest rates compared to traditional banks. Non-Custodial Savings: Users have full control over their funds, reducing the risk of losing their money to institutional failures or fraud. Access to DeFi: Integrating with DeFi platforms like Moola Market, HaloFi Save provides additional opportunities to earn interest on savings, promoting financial growth and stability. Practical Example: A Farmer's Journey Imagine a farmer in a remote village in Africa. Traditionally, this farmer might not have access to banking services, making it difficult to save money, get loans, or invest in better farming equipment. With platforms like HaloFi Save, the farmer can: Save money securely and earn interest. Access microloans through DeFi platforms integrated with Celo. Participate in educational programs to learn more about blockchain and DeFi. Conclusion Blockchain technology, through platforms like HaloFi Save and initiatives by Celo Africa DAO, has the potential to drive significant social change by promoting financial inclusion, transparency, and access to resources. By empowering individuals and communities with the tools and knowledge to participate in the digital economy, blockchain can help address global issues and foster sustainable development.

Reading Passage: The Anatomy of a Kill Chain In the lexicon of modern warfare, the term "kill chain" describes the end-to-end process of a military attack, from the initial identification of a target to its eventual destruction and the subsequent evaluation of the strike's effectiveness. Conceptually, the kill chain is a structural model used to understand and optimize the speed and precision of military operations. The fundamental principle of this model is that an attack functions as a sequence of interdependent stages; if any single link in the chain is broken, the entire operation fails. For strategic planners, this creates a dual objective: to accelerate one's own kill chain while simultaneously finding ways to disrupt the adversary's. Strategic Concept: The Kinetic Model (F2T2EA) The traditional military kill chain is often summarized by the acronym F2T2EA, representing a continuous cycle of find, fix, track, target, engage, and assess. The kinetic kill chain begins with Find, the reconnaissance phase where intelligence assets identify a potential target within a theater of operations. Once found, the process moves to Fix, which involves pinning down the target's specific location and ensuring it can be distinguished from friendly forces or non-combatants. Track follows, maintaining a persistent watch on the target's movements to prevent its escape. In the Target phase, commanders select the appropriate weapon system and verify the legality and strategic value of the strike. Engage is the kinetic moment—the actual deployment of ordnance against the objective. Finally, Assess involves battle damage assessment (BDA) to determine if the desired effects were achieved or if further engagement is required. This model emphasizes "compressing the sensor-to-shooter timeline," meaning the faster a military can move through these steps, the more lethal it becomes. The Evolution: The Cyber Kill Chain® As warfare expanded into the digital domain, Lockheed Martin adapted the kinetic model into the Cyber Kill Chain. This framework assists defenders in identifying and stopping Advanced Persistent Threats (APTs). Unlike a physical missile, a cyberattack often unfolds over weeks or months, but the sequential logic remains the same. The model consists of seven distinct stages: Stage Description of Attacker Activity 1. Reconnaissance The harvesting of information. Attackers research targets via social media, public records, and technical scanning to find vulnerabilities. 2. Weaponization Coupling a remote access trojan with an exploit into a deliverable payload (e.g., a malicious PDF or Microsoft Office document). 3. Delivery Transmission of the weapon to the target environment. Common vectors include email attachments, malicious websites, or USB drives. 4. Exploitation The weapon triggers. The code executes on the victim's system, typically by taking advantage of a software or operating system vulnerability. 5. Installation The attacker installs a persistent backdoor or malware on the victim's system, allowing them to maintain access even after a reboot. 6. Command & Control (C2) The compromised system opens a communication channel back to the attacker's server, allowing the intruder to give manual instructions. 7. Actions on Objective The final stage where the attacker achieves their goal, such as data exfiltration, encryption for ransom, or destruction of critical infrastructure. Strategic Implications for Defense The strategic value of the Cyber Kill Chain lies in its ability to provide a roadmap for "proactive defense." By understanding the sequence, security professionals can implement controls at every stage. For instance, robust email filtering can break the chain at the Delivery stage, while endpoint detection can stop the Installation phase. Crucially, the earlier a defender breaks the chain, the lower the cost of mitigation and the lower the risk of damage. If an attacker is stopped during Reconnaissance, they have gained nothing. If they are stopped during Actions on Objective, the damage may already be catastrophic. In both kinetic and cyber environments, the goal is the same: to create a "defensive depth" that makes the cost of a successful attack prohibitively high for the adversary.

DIMENSIONS of Wellness - social, spiritual, emotional/mental, environmental, financial, intellectual, multicultural, occupational, physical, sexual RISK factors - anything that increases the risk of disease, injury, or illness. PROTECTIVE factors - anything that decreases the risk of disease, injury, or illness. INTERNAL health factors - health factors that can be either hereditary and genetic or acquired elements -- include smoking and personal diet or eating habits. Example – a genetic predisposition to an illness. EXTERNAL health factors - health factors that are part of the direct outer environment, the geographical location, micro-organisms, socio-economic elements that could affect an individual's health. Example – being unable to afford mental health services.

Online shopping is Amazing. Or is it? So many shower curtains! But with the endless choice comes the risk of being fooled.

Chapter 22 Antihypertensive Drugs Hypertension Defined (JNC-8) Pharmacology Overview 7 main categories of drugs to treat HTN Adrenergic drugs (old friend) Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Vasodilators Direct renin inhibitors A. Adrenergic Drugs: 5 Subcategories and where they act A1. Adrenergic neuron blockers (central and peripheral)- we won’t talk about this A2. Alpha1 receptor blockers (peripheral) A3. Alpha2 receptor agonists (central) A4. Beta receptor blockers (peripheral) A5. Combined α and β receptor blockers (peripheral) A2. Peripherally Acting Adrenergic DrugAlpha1 Blockers (we’ve met these) Doxazosin, prazosin, alfuzosin Block alpha1-receptors which causes BP to decrease Reduces peripheral vascular resistance and BP by dilating both arterial and venous blood vessels Main Use: benign prostatic hyperplasia (BPH) Alpha1 Blockers REMEMBER Tamsulosin (Flomax)* is an α1 blocker BUT *Tamsulosin is not used to control BP, just for BPH. A3. Centrally Acting Adrenergic DrugsAlpha 2 agonist Clonidine and methyldopa 1- Stimulate alpha2-adrenergic receptors. in the brain Decreases sympathetic outflow from the CNS which decreases NE production 2. Stimulate alpha2-adrenergic receptors in kidneys remember alpha 2 opposes alpha 1 Dilates peripheral blood vessels → lowers peripheral resistance → Results in decreased BP So ….Clonidine (Catapres) Used primarily for its ability to decrease blood pressure in an urgent setting Also use in opioid withdrawal as previously discussed Oral (multiple times a day), and topical patch formulations Do not stop abruptly as it may lead to rebound hypertension In reality, Clonidine and methyldopa Not prescribed as first-line home antiHTN drugs High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness MIGHT be uses as adjunct drugs after other drugs have failed, in conjunction with other antiHTN such as diuretics A4. Adrenergic Drugs Selective Beta 1 Blockers Metoprolol, Atenolol Reduction of HR through β1 receptor blockade (remember adrenergic blocking of this receptor???) HR results in BP Cause reduced secretion of renin = BP A4. Adrenergic Drugs Selective Beta1 Blockers Nebivolol (Bystolic) Uses: hypertension and HF Action: blocks β1 receptors and produces vasodilatation, which results in a decrease in SVR High doses loses selectivity and blocks both β1 and β2 Less sexual dysfunction All BB- Do not stop abruptly; must be tapered over 1 to 2 weeks A4. Adrenergic Drugs NONSelective Beta Blockers Propranolol Acts equally on β1 and β2 Other uses include situational anxiety associated with public speaking, test taking As mentioned on previous slide, nebivolol at high doses becomes beta nonselective A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade) Examples are carvedilol (common) and labetalol (not as common) A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Carvedilol (Coreg) Widely used drug that is well tolerated Uses: HTN, mild to moderate HF in conjunction with digoxin, diuretics, and ACE inhibitors Contraindications: severe bradycardia or unstable HF, bronchospastic conditions such as asthma, and various cardiac conduction problems Adrenergic Drugs Indications - HTN But also for Glaucoma (topical) BPH: doxazosin, prazosin, and terazosin (2 for 1) Management of severe HF when used with cardiac glycosides and diuretics Contraindications Acute HF- have to stabilize first MOAIs- yeah doesn’t everything interact with MAOIs? Peptic ulcers Severe liver/kidney disease Asthma (with beta blockers) Adrenergic Drugs: Adverse Effects Orthostatic hypotension 1st-dose syncope Rebound hypertension with abrupt discontinuation Most common: Dry mouth, drowsiness, constipation, sedation Interactions- always check for specific drug interactions Can cause additive CNS depression with alcohol, benzodiazepines, opioids Question #1 When administering an alpha-adrenergic drug for hypertension, it is most important for the nurse to assess the patient for the development of what response? Hypotension Hyperkalemia Oliguria Respiratory distress Answer A Hypotension This is a key point in patient education These drugs have strong vasodilating properties and may cause severe hypotension, especially at the beginning of therapy. B. Angiotensin-Converting Enzyme Inhibitorsaka ACE Inhibitors or ACEi Large group of safe and effective drugs Currently are 10 ACEi Often used as first-line drugs for HF and hypertension May be combined with a thiazide diuretic, loop diuretic, or Calcium Channel Blocker (CCB) You need to understand the basics ACE Inhibitors: Review RAAS ACE converts angiotensin I, formed through the action of renin, to angiotensin II Angiotensin 2 is a potent vasoconstrictor and also induces aldosterone secretion by the adrenal glands Aldosterone stimulates sodium resorption (H20 follows Na Both act to raise BP which causes kidneys to reduce renin production ACEi= Great drug to treat HTN BUT contraindicated in pregnancy (2nd,3rd trimester due to fetal renal damage) and breastfeeding first few weeks after birth B. ACE Inhibitors - PRIL Lisinopril (Prinivil) super common, often the 1st drug Enalapril (Vasotec) also common Captopril (Capoten) great if liver disease present Benazepril (Lotensin) Fosinopril (Monopril) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Primary Effects of the ACE Inhibitors Prevent Na (and H2O) resorption by inhibiting aldosterone secretion (volume reduction) (GO BACK TO RAAS DIAGRAM) blood volume decreases work of the heart preload, or the left ventricular end-diastolic volume which is important in HF ACE SUMMARY OF ACTIVITY 1) Prevent vasoconstriction caused by angiotensin 2 (2) Prevent aldosterone secretion  less sodium and water resorption Cardioprotective Effects of ACEi They slow progression of left ventricular hypertrophy (ventricular remodeling) after MI so considered cardioprotective ACE inhibitors have been shown to decrease morbidity and mortality in patients with HF Renal Protective Effects of ACEi ACE inhibitors: reduce glomerular filtration pressure by volume reduction Cardiovascular drug of choice for patients with diabetes since it helps protect kidneys by reducing pressure. Sometimes used low dose for kidney protection with DM without HTN B. ACEi Enalapril (Vasotec) Only ACEi available in both oral and IV Enalapril IV does not require cardiac monitoring Oral enalapril: prodrug (metabolized in liver) Improves patient’s chances of survival after an MI Reduces the incidence of HF B. ACEi Captopril (Capoten) Uses: prevention of ventricular remodeling after MI; reduce the risk of HF after MI Shortest half-life Must be administered multiple times throughout the day so this limits its use Not a prodrug so good for patient with liver disease Question #2 A patient with diabetes has a new prescription for the ACE inhibitor lisinopril. She questions this order because her provider has never told her that she has hypertension. What is the best explanation for this order? The doctor knows best The patient is confused This medication has cardioprotective properties This medication has a protective effect on the kidneys for patients with diabetes Answer D ACE inhibitors have been shown to have a protective effect on the kidneys because they reduce glomerular filtration pressure. This property makes them the cardiovascular drug of choice for patients with diabetes. Question #3 A patient with a history of pancreatitis and cirrhosis is also being treated for hypertension. Which drug will most likely be ordered for this patient? Clonidine Prazosin Diltiazem Captopril Answer D Captopril Captopril is not a prodrug; therefore, it does not need to be metabolized by the liver to be effective. This is an advantage in patients with liver disease. ACE Inhibitors: Adverse Effects *Dry, nonproductive cough, which reverses when therapy is stopped. This is a class effect Dizziness- Note: First-dose hypotensive effect may occur Headache & Fatigue Possible hyperkalemia ** Angioedema: rare but potentially fatal Not safe in pregnancy-are contraindicated during the second and third trimesters of pregnancy because of increased risk of fetal renal damage C. Angiotensin II Receptor Blockers(ARB) Considered an alternative to ACEi Less likely to cause a dry cough and hyper K+ that is common with ACE inhibitors Angiotensin II Receptor Blockers: Mechanism of Action Go back to RAAS diagram! ARBs affect primarily 2 places 1. Vascular smooth muscle - blocks vasoconstriction 2. Adrenal gland -Selectively blocks the binding of Ang 2 to certain Ang 2 receptors inhibiting secretion of aldosterone Lowers volume retention and BP Angiotensin II Receptor Blockers -ARTAN Losartan (Cozaar)- very common Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis) Azilsartan (Edarbi) C. ARB Losartan (Cozaar) Beneficial in patients with HTN and HF Used with caution in patients with kidney or liver dysfunction and in patients with renal artery stenosis ***Not safe for breastfeeding women and should not be used in pregnancy (Cat C 1st trimester, Cat D 2nd-3rd trimester), potential fetal toxicity Appear to be equally effective for the treatment of hypertension and well tolerated ARBs less likely to cause cough and hyperK+ but can still happen Evidence that ARBs are associated with lower mortality after MI than ACE inhibitors Never take ACEi and ARBs at the same time* 5. Calcium Channel Blockers (CCB) Primary use: HTN, angina, some dysrhythmias Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction Results in: Relaxed blood vessels to the heart Decreased peripheral smooth muscle tone Decreased SVResistance Decreased BP E. Diuretics First-line antiHTN in JNC 8 guidelines Decreases fluid volume The results from diuresis: preload, Peripheral resistance Overall effect  Decreased workload of the heart and decreased BP Thiazide diuretics are the most commonly used diuretics for HTN Ie hydrochlorothiazide (HCTZ), chlorthalidone We will discuss diuretics further in the chapter on diuretics F. Vasodilators Directly relax arterial or venous smooth muscle (or both) Results in: Decreased SVR Decreased afterload Peripheral vasodilation Indicated for treatment of HTN May be used in combination with other drugs F. Vasodilators Hydralazine (Apresoline) Orally: routine cases of essential hypertension Injectable: hypertensive emergencies BiDil: specifically indicated as an adjunct for treatment of HF in African-American patients F. Vasodilators Sodium Nitroprusside (Nitropress) *Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies. Contraindications: severe HF, known inadequate cerebral perfusion (especially during neurosurgical procedures) F. Vasodilators Adverse Effects Hydralazine: dizziness, headache, tachycardia, edema, dyspnea, N/V/D, vitamin B6 deficiency, rash Sodium nitroprusside: hypotension, bradycardia, decreased platelet aggregation, rash G. Direct Renin Inhibitors Aliskirin (Tekturna) Blocks the RAS pathway at the point of activation. Inhibiting renin production prevents the downstream production of Ang II (potent vasoconstrictor) Adverse effects: N/V, severe hypotension, hyponatremia, hyperkalemia… Contraindicated in patients with DM taking ACEi or ARB Miscellaneous Antihypertensives Eplerenone (Inspra) Newer class of drugs called selective aldosterone blockers (remember RAAS?) Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain Indications: routine treatment of hypertension and for post-MI HF Contraindicated if serum potassium levels are high (above 5.6 mEq/L) A Special Form of HTNTreatment of Pulmonary Hypertension Sildenafil and Tadalafil Commonly used for erectile dysfunction Used for pulmonary hypertension but with different trade names Sildenafil: Revatio* (Viagra for ED) Tadalafil: Adcirca* (Cialis for ED)

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