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An outbreak of hepatitis in New Delhi was characterized by high incidence of fulminant hepatitis in pregnant women, who experienced a mortality rate of 20%. The virus responsible for the outbreak: A. Is an unenveloped RNA virus (%) B. Is transmitted parenterally (%) C. Is associated with chronic hepatitis (%) D. Infects only HBsAg-positive individuals (%) E. Has oncogenic properties (%)

A. Is an unenveloped RNA virus (%) Hepatitis E virus is an unenveloped, single-stranded RNA virus spread through the fecal-oral route. Infection with HEV occurs primarily in young and middle-aged adults living in Asia, sub-Saharan Africa, and Mexico, with an average incubation period of six weeks. While the virus is shed in the stool during the acute illness, the disease is typically self-limited and not associated with either chronic liver disease or a carrier state. HEV Ag or HEV RNA can be detected in the stool or liver in the earliest stages of infection (when the patient is asymptomatic). Later, serum transaminases and IgM anti-HEV titers rise in association with clinical illness. The most concerning feature of hepatitis E is the high mortality rate observed in infected pregnant women.

A 52-year-old woman comes to the clinic to discuss the results of a recent abdominal CT scan. The patient says, "I hope the scan can tell me why I've been losing so much weight. What does it show?" The physician shares that the imaging is suggestive of pancreatic cancer. Upon hearing this, the patient begins to cry while holding her head in her hands. Which of the following is the most appropriate response by the physician? A. "I know this isn't the news you wanted to hear. Let's talk about the results in a bit more detail." (%) B. "I wish I had better news to share with you. I imagine this is very upsetting to hear." (%) C. "It's easy to feel lonely and isolated with news like this. Tell me about the people who support you during difficult times." (%) D. "This must feel very shocking and unexpected. Fortunately, there have been some advances in treatment recently." (%) E. "This news would be upsetting to anyone. Let's set up an appointment to discuss the next steps in a few days." (%)

B. "I wish I had better news to share with you. I imagine this is very upsetting to hear." (%) In this case, the physician has just delivered serious news and must respond sensitively to a crying patient. The most appropriate response is to acknowledge the patient's distress, express empathy, and allow the patient time to process the news. The patient should be allowed to cry without redirection of the conversation or assumption about how much information she wants to know at this point. Once the patient is able to converse, the physician can gently explore her feelings and respond to any questions, allowing the patient to take the lead in the discussion (eg, ask the patient how much information she would like to know at this point). Models have been developed to guide clinicians in delivering serious news. The SPIKES protocol, originally developed for cancer patients, can be adapted to conversations with patients in many situations (eg, medical futility discussion, STI results).

56-year-old man comes to the office for follow-up of type 2 diabetes mellitus. He has an extensive family history of complicated type 2 diabetes, and multiple family members have required lower extremity amputations for nonhealing ulcers. The patient has tried multiple oral medications and his most recent hemoglobin A1c is 9.6%. He is now being considered for basal insulin therapy. After an extended discussion of injection technique, the patient tells the clinician that he does not want to initiate insulin. He says, "My diabetes is my own fault. My mother always said I was too fat and was going to get diabetes like my dad. Maybe if I stop eating too much, I wouldn't have to waste your time giving me insulin." Which of the following is the most appropriate response to this patient's statement? A. "Insulin is the best option for your diabetes right now, and we can work on weight loss later." (%) B. "It is common for people with diabetes to eventually need insulin. That doesn't mean it is your fault." (%) C. "It seems you are becoming frustrated with your health. Do you feel like you may be depressed?" (%) D. "You should never feel like you are wasting my time. Helping patients get better is what makes me happy." (%) E. "You shouldn't blame yourself. Your family history is not something you can control." (%)

B. "It is common for people with diabetes to eventually need insulin. That doesn't mean it is your fault." (%) Failure of oral medications is common in long-standing type 2 diabetes mellitus due to progressive loss of pancreatic beta cell function. Basal insulin therapy is often necessary, especially when multiple agents have failed or when a patient has a hemoglobin A1c >9%. It is common for patients to have reservations about initiating insulin due to treatment complexity, risk of hypoglycemia, or injection pain. However, this patient is expressing concern that the failure of oral agents represents a personal inadequacy; in other words, he thinks that his diabetes is uncontrolled because he has failed to follow lifestyle recommendations (ie, diet). In counseling patients with treatment failure, especially those who have overpersonalized their medical condition, it is appropriate to review the natural history of the condition. In this case, the clinician should explain that type 2 diabetes is a progressive disorder and that escalating treatment regimens are often the norm. Lifestyle factors (eg, diet, weight loss) should not be neglected but should be discussed in a compassionate, nonjudgmental way, and self-blame should not be encouraged.

A 43-year-old man comes to the office due to shortness of breath and fatigue. Over the last 2 weeks, his fatigue has been so profound that he has "little energy, even to get out of bed." The patient has no chills but has experienced recent weight gain and ankle swelling. He has no prior medical conditions and takes no medications. Blood pressure is 168/94 mm Hg, and pulse is 95/min and regular. The patient has bilateral lower extremity pitting edema limited to the ankles. Urinalysis reveals 2+ protein, white blood cell count of 5-7/hpf, and red blood cell count of 75-100/hpf. He undergoes a kidney biopsy; immunofluorescent microscopy findings are shown in the image below. (linear immune deposition) Which of the following would be the most likely finding on light microscopy in this patient? A. Amyloid deposition (%) B. Crescent formation (%) C. Diffuse capillary wall thickening (%) D. Nodular glomerulosclerosis (%) E. Normal glomeruli (%)

B. Crescent formation (%) This patient has hypertension, hematuria (with mild pyuria), and moderate proteinuria, suggesting a diagnosis of nephritic syndrome. Immunofluorescence microscopy further demonstrates linear deposits of immunoglobulin (typically IgG) and complement along the glomerular basement membrane (GBM), a finding characteristic of anti-GBM disease (Goodpasture disease). Anti-GBM antibodies target collagen type IV, a component of the GBM, leading to subsequent complement deposition. This results in a form of rapidly progressive (crescentic) glomerulonephritis (RPGN). RPGN is a syndrome of severe renal injury that results in abrupt-onset renal injury and decreased glomerular filtration (causing weight gain and edema, as seen in this patient). It can occur due to multiple diseases (eg, granulomatosis with polyangiitis, microscopic polyangiitis). The presence of glomerular crescents—composed of proliferating parietal cells, lymphocytes, macrophages, and fibrin—on light microscopy is diagnostic. Anti-GBM antibodies may cross-react with collagen type IV in the pulmonary alveolar basement membrane and cause pulmonary hemorrhage, which presents as hemoptysis. The combination of renal failure and pulmonary hemorrhage in patients with anti-GBM antibodies is known as Goodpasture syndrome

A 6-year-old African American male is brought to your office for a routine check-up. His mother remarks that he often seems uninterested in playing with his peers and appears to "run out of breath quickly." His medical records reveal that he has missed several pediatric vaccinations and has been hospitalized twice, once with a "chest infection" and once with abdominal pain. The patient mentions to you that occasionally his "bones hurt." Which of the following protein changes most likely accounts for this patient's condition?

B. Valine substitution for glutamic acid

A healthy 31-year-old woman comes to the office as she and her husband desire a second child. The husband is infertile and the patient's son, who was conceived via donor insemination, was recently diagnosed with glycogen storage disease type II (Pompe disease). This rare autosomal recessive disease is known to affect 1 in 40,000 of the general population. Genetic testing confirms that the patient is a carrier for the disease. A different sperm donor is selected with no personal or family history of Pompe disease; however, his carrier status is unknown. What is the probability of the patient having an affected child with the new sperm donor? A. 1/4 (%) B. 1/240 (%) C. 1/400 (%) D. 1/800 (%) E. 1/40,000 (%) F. 1/160,000 (%)

C. 1/400 (%) q^2= 1/40,000 q= 1/200 chances he's a heterozygous carrier= 2pq (just use 1 for p) 2pq* 1/4 chance their kid is autosomal recessive

Researchers analyze the HIV viral structure and replication cycle for new drug targets. They find the virus encodes a large glycoprotein, which gets cleaved into 2 subunits, the surface and transmembrane subunits. These subunits remain noncovalently bound to each other in the virion. Upon activation of the surface protein, conformational changes occur in the transmembrane subunit exposing the functional inner core. A novel drug is developed that selectively binds and prevents normal functioning of the transmembrane subunit, interfering with the normal viral replication cycle. This agent most likely directly inhibits which of the following viral processes? A. Attachment of the virus to target cell surface (%) B. Budding and release of a new virus particle (%) C. Cleavage of polyproteins by viral encoded enzyme (4%) D. Entry of the viral core into host cytoplasm (%) E. Integration of the viral DNA into host genome (%) F. Synthesis of DNA from viral RNA template (%) G. Transcription of mRNA from proviral DNA (%)

D. Entry of the viral core into host cytoplasm (57%) The HIV genome encodes several enzymes and structural proteins in polycistronic mRNAs that are then translated into polyproteins and cleaved by proteases into the individual proteins that compose the virus. The env gene encodes the polyprotein gp160, which is extensively glycosylated in the endoplasmic reticulum and Golgi body and subsequently cleaved into the mature envelope proteins gp120 and gp41. These envelope proteins remain associated by noncovalent attachments and form the glycoprotein spikes that pepper the surface of the HIV virus. gp120 forms the outside surface of the glycoprotein spike and mediates viral attachment to the host cell by binding with the CD4 receptor and a chemokine coreceptor (CXCR4, CCR5) (Choice A). Binding of gp120 to these host receptors induces a conformational change in the structure of the glycoprotein spike that exposes the underlying transmembrane glycoprotein gp41. gp41 mediates fusion of the viral cell membrane with the host cell membrane, thereby allowing the viral core to enter the cell. Drugs that selectively bind gp41 (eg, enfuvirtide) are known as fusion inhibitors because they prevent gp41 from undergoing the conformational changes necessary for viral fusion, which prevents the HIV genome from entering uninfected cells.

44-year-old man is brought to the hospital with fatigue, shortness of breath, and lethargy. The patient had a brief upper respiratory illness about a month ago but began experiencing progressive dyspnea on exertion 2 weeks ago. He has no significant medical history and takes no medications. Blood pressure is 100/70 mm Hg; pulse is 95/min and regular. The apical impulse is palpated in the sixth intercostal space along the left anterior axillary line. An S3 is heard on cardiac auscultation. Bibasilar crackles are present. Distal extremities are cold to touch and there is 1+ peripheral edema. Laboratory results are as follows: Blood urea nitrogen 45 mg/dL Serum creatinine 1.8 mg/dL Urine microscopy Red blood cells 0/hpf White blood cells 0-1/hpf Sediment none seen Which of the following is likely to be present in this patient compared to the normal state? A. Decreased distal tubule sodium reabsorption (%) B. Decreased proximal tubule urea reabsorption (%) C. Decreased renal venous pressure (%) D. Increased collecting duct free water excretion (%) E. Increased proximal tubular sodium reabsorption (%) F. Increased renal blood flow (%)

E. Increased proximal tubular sodium reabsorption (%) This patient with a recent upper respiratory infection has developed dyspnea, lower extremity edema, and an S3 on cardiac exam; this presentation suggests dilated cardiomyopathy with decompensated heart failure (CHF), likely from viral myocarditis. Renal decompensation (acute kidney injury or chronic kidney disease) occurs in up to 60% of patients with CHF and is often due to a complex syndrome known as cardiorenal syndrome. The pathophysiology of cardiorenal syndrome is multifactorial and includes both hemodynamic alterations related to the low output state and resultant neurohormonal changes. Decreased cardiac output results in renal hypoperfusion, which triggers the following adaptations: Renin-angiotensin-aldosterone system (RAAS) activation, leading to increased proximal tubular sodium reabsorption (direct effect of angiotensin II) Antidiuretic hormone release, resulting in increased free water reabsorption in the collecting ducts Sympathetic nervous system activation, resulting in systemic vasoconstriction In the short-term, these adaptions increase the effective arterial blood volume and maintain systemic perfusion, allowing for a relatively normal glomerular filtration rate. However, over time, widespread vasoconstriction increases the afterload (ie, the resistance the heart must pump against) and ventricular overfilling leads to decreased pump efficiency, lowering cardiac output and furthering renal hypoperfusion. At a certain point, the decrease in cardiac output becomes overwhelming and glomerular filtration rate begins to drop. Characteristic laboratory findings in cardiorenal syndrome reflect activation of the RAAS and indicate a prerenal etiology, with low urine sodium and fractionated excretion of sodium (<1%). Urea is passively reabsorbed following sodium in the proximal tubule, leading to an elevated blood urea nitrogen/creatinine ratio (>20:1).

On physical examination, jugular venous pressure is elevated, breath sounds are decreased at the right lung base with dullness to percussion, and 2+ bilateral lower extremity pitting edema is present. Chest x-ray shows cephalization of the blood vessels, Kerley B lines, and a right pleural effusion. Thoracentesis is performed for pleural fluid analysis. In comparison to plasma fluid, which of the following pleural fluid findings is most likely to be observed? A. High amylase content (%) B. High protein content (%) C. High white blood cell count (%) D. Low glucose content (%) E. Low lactate dehydrogenase content (%)

E. Low lactate dehydrogenase content (%) In determining the etiology of a pleural effusion, differentiating whether the effusion is transudative or exudative is an important step. The Light criteria allows differentiation of these two types of effusion via analysis of the protein and lactate dehydrogenase levels of the fluid. Transudative pleural effusions form due to an imbalance in hydrostatic or oncotic pressure. Heart failure causes increased hydrostatic pressure in the pulmonary circulation due to backup of blood flow from the failing left ventricle. This increased pressure leads to leakage of fluid from the pulmonary capillaries and causes a transudative pleural effusion, which is characterized by low protein and low lactate dehydrogenase levels compared to serum values. In contrast, exudative effusions result from inflammatory disruption of vascular permeability (eg, infection, malignancy) and demonstrate high protein levels (Choice B) due to increased capillary permeability and reduced sieving of proteins as fluid traverses the capillary wall. Lactate dehydrogenase levels also tend to be high in exudative effusions

A 28-year-old woman is treated with high-dose prednisone for severe lupus nephritis. Several hours after therapy is initiated, she becomes very agitated and delusional. Blood pressure is 130/70 mm Hg and heart rate is 110/min. A basic metabolic profile, complete blood cell (CBC) count, and urinalysis are obtained. The CBC differential is expected to show an increase in which of the following as a result of this patient's therapy? A. Basophils (%) B. Eosinophils (%) C. Lymphocytes (%) D. Monocytes (%) E. Neutrophils (%)

E. Neutrophils (%) As a result of their immunosuppressive effects, corticosteroids such as prednisone have been used to treat many autoimmune and inflammatory conditions, including systemic lupus erythematous. However, corticosteroid use can lead to a number of adverse effects. High doses can sometimes cause corticosteroid-induced psychosis (confusion, hallucinations), as seen in this patient; hypoalbuminemia is a risk factor, and the neuropsychiatric symptoms typically resolve with discontinuation of therapy. Corticosteroid receptors also have widespread physiologic effects, including those on circulating leukocytes and vascular endothelial cells. Neutrophil counts increase following administration of the drug as a result of "demargination" of neutrophils previously attached to the vessel wall. Therefore, neutrophil recruitment to fight infection in tissues is decreased, potentially contributing to increased infection risk.

Researchers want to study the effects of labyrinthectomy with cochlear implantation on hearing, vertigo, and tinnitus. A random sample of medical charts is selected from a cohort of patients who had undergone labyrinthectomy with cochlear implantation in the same ear for intractable vertigo and hearing loss and who had documentation of both preoperative and postoperative audiometric evaluations. Tinnitus is quantified using the Tinnitus Handicap Inventory (THI) before and after the interventions. The THI score ranges from 0 to 100, with higher values indicating greater tinnitus severity. Which of the following statistical tests is most appropriate for comparing preoperative and postoperative THI scores? A. Analysis of variance (%) B. Chi-square test (%) C. Correlation analysis (%) D. Meta-analysis (%) E. Paired t-test (%) (Choice A) The analysis of variance (ANOVA) test compares the mean of ≥3 independent groups, as in a study comparing serum ferritin concentrations (ie, quantitative variable) in children (age 0-17), adults (age 18-59), and seniors (age ≥60). (Choice B) The chi-square test evaluates the association between 2 categorical variables, as in a study evaluating the association between sex (ie, "male" and "female") and myocardial infarction (ie, presence or absence). (Choice C) A correlation analysis uses the correlation coefficient to describe the linear relationship between 2 quantitative variables, as in a study evaluating the linear relationship between hours of sleep and irritability score. (Choice D) Meta-analysis is a statistical technique used to combine and analyze data from several studies to conduct an analysis with a greater statistical power than that of the individual studies. Educational objective:The paired t-test compares the mean of 2 related groups. The test requires that a quantitative dependent variable (ie, outcome) be evaluated in 2 related (ie, matched, paired) groups.

E. Paired t-test (%) A t-test compares the mean of 2 groups. It requires that a quantitative dependent variable (ie, outcome) be evaluated in 2 groups that are classified based upon a categorical independent variable (ie, exposure). In this study: The quantitative dependent variable was the Tinnitus Handicap Inventory (THI) score. The categorical independent variable was the audiometric evaluation (with categories "preoperative" and "postoperative"). A t-test will determine whether there is a statistically significant difference in mean THI scores between the preoperative and postoperative audiometric evaluations. A large, statistically significant difference in mean scores indicates that labyrinthectomy with cochlear implantation is associated with changes in tinnitus (ie, the null hypothesis is rejected). There are 2 types of t-tests: the independent samples t-test (used when 2 groups are independent) and the paired t-test (used with 2 related groups with matched pairs). Matched groups are formed when each observation in one group is paired with an observation from the other group. Examples include a study in which individuals have been assessed twice (eg, before and after an intervention) and one in which 2 groups of individuals have been matched based on certain attributes (eg, age, severity of disease). In this case, THI scores are assessed twice for each patient (preoperative and postoperative audiometric evaluations); therefore, a paired t-test is used

A 12-year-old boy is brought to the emergency department due to a skin infection. Temperature is 38.4 C (101.1 F). Physical examination shows an area of erythema, warmth, and tenderness on his right distal leg. Laboratory results are notable for leukocytosis. The patient is started on intravenous nafcillin. Two days later, he shows limited response to antibiotic therapy. Light microscopy of pus obtained from the site shows gram-positive cocci in clusters, and sensitivity testing demonstrates little response to nafcillin but good response to vancomycin. Which of the following is the most likely explanation for nafcillin treatment failure in this patient? A. Active drug transport out of the cell (%) B. Enzymatic degradation of the drug (%) C. Mutation in DNA gyrase (%) D. Mutation in RNA polymerase (%) E. Poor interaction with binding proteins (%)

E. Poor interaction with binding proteins (%) The presence of gram-positive cocci in clusters that do not respond to nafcillin but show sensitivity to vancomycin suggests infection with methicillin-resistant Staphylococcus aureus (MRSA). S aureus is a common cause of skin infections in the United States. Most skin infections are minor, but S aureus can cause serious infections (eg, surgical wound infections, bloodstream infections in the presence of central intravenous catheters, pneumonia). S aureus strains that are resistant to oxacillin, nafcillin, and methicillin have been historically termed MRSA, but they are also resistant to all β-lactam agents, including penicillin, cephalosporins (except ceftaroline, a fifth-generation cephalosporin), and carbapenems. Methicillin (nafcillin) resistance is typically mediated by alterations in the structure of penicillin-binding proteins (PBP), the enzymes involved in cell wall synthesis. Altered PBPs, especially PBP2a, have greatly reduced affinity for β-lactam antimicrobial agents (except ceftaroline)

A surveillance study is conducted to assess the efficacy and safety of tolvaptan, a drug currently being used in the clinical setting for treating heart failure with volume overload. The study enrolls 8,300 patients with a variety of medical comorbidities who received tolvaptan once daily in the morning for 2 weeks. Results showed that tolvaptan demonstrated aquaretic efficacy in patients with diuretic-resistant volume overload, but that hypernatremia was a complication in a small number of patients. Researchers recommended a lower dose of tolvaptan in those with normonatremia and hypokalemia to prevent hypernatremia. Which of the following best describes this type of study? A. Preclinical study (0%) B. Phase I clinical trial (6%) C. Phase II clinical trial (25%) D. Phase III clinical trial (28%) E. Phase IV clinical trial (38%)

Phase IV trials are postmarketing surveillance studies that assess the adverse effects and long-term effectiveness of newly approved treatments on the market. Results from phase IV trials may lead to restrictions in use or a withdrawal of treatment from the market. The clinical trials process addresses whether new treatments (eg, drugs, procedures) are effective and safe for their intended use (ie, treatment of a disease) in the target population (eg, subjects with the disease of interest). New treatments go through several research phases; some phases involve no human subjects (ie, preclinical studies) and some involve few (ie, phase I and II trials) or many (ie, phase III and IV trials) human subjects. Phase IV trials are postmarketing surveillance studies that assess for rare or delayed adverse effects of newly approved treatments on the market. They are conducted on larger patient populations for longer periods of time compared to other types of clinical trials. As such, they have substantial statistical power and can identify adverse effects that were not observed in earlier trials; they may also evaluate long-term effectiveness of new treatments and assess treatment response in different subpopulations (eg, based on sex, comorbidities). Results from phase IV trials may lead to restrictions in use or a withdrawal of treatment from the market. In this example, a postmarketing surveillance study was conducted to determine if the efficacy and safety features established in controlled trials for a treatment (ie, tolvaptan) in a particular population (ie, heart failure subjects with volume overload) extend to real-world clinical settings. The study revealed a treatment complication in the clinical setting (ie, hypernatremia) that warranted a use restriction (ie, lower dose) in a specific population (ie, those with normonatremia and hypokalemia). This study describes a phase IV trial.

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S3 at point D When present, a third heart sound (S3) occurs during diastole and is best heard with the bell of the stethoscope over the cardiac apex with the patient in the left lateral decubitus position. It is due to sudden limitation of ventricular movement during passive ventricular filling. An S3 may be a normal finding in healthy young adults; however, in patients age >40 it suggests abnormal ventricular cavity enlargement (ie, eccentric hypertrophy). An S3 is often associated with chronic severe mitral regurgitation, chronic aortic regurgitation, or dilated cardiomyopathy; occasionally, it may be present in high cardiac output states such as pregnancy or thyrotoxicosis.

Most patients do not require medical attention as vWD symptoms are typically mild. However, those who need treatment can receive desmopressin (or 1-desamino-8-d-arginine vasopressin [DDAVP]), a synthetic analog of vasopressin (ie, antidiuretic hormone [ADH]), which is normally released by the posterior pituitary. DDAVP increases

vWF release from endothelial cells. DDAVP also raises factor VIII levels and is used for the treatment of mild hemophilia A. Hemophilia is an X-linked coagulation disorder and is unlikely in this patient given the clear autosomal dominant pattern of inheritance (father and paternal grandmother)