Ophthalmology Residency Program Director Survey on Pass/Fail U.S. Medical Licensing Exam Step 1 Scoring.

Background Beginning January 26, 2022, the U.S. Medical Licensing Exam (USMLE) Step 1 changed from a numerical score to pass/fail (P/F). The purpose of this study was to determine the perspective of ophthalmology program directors regarding this change in evaluating applicants. Methods After institutional review board approval, a survey was sent out to program directors of all 125 ophthalmology programs accredited by the Accreditation Council for Graduate Medical Education. Survey questions asked for program demographics, the utility of USMLE Step 1 and 2 Clinical Knowledge scores in assessing applicants, and the importance of 16 different applicant metrics before and after Step 1 becomes P/F. The metrics examined were: letters of recommendation; clerkship grades; class ranking; Alpha Omega Alpha Membership; Gold Humanism Honor Society Membership; Dean's Letter; involvement and leadership; personal statement; number of abstracts, presentations, and publications; mean number of research experiences in the specialty; Step 2 Clinical Knowledge score; volunteering; preclinical grades; away rotation in the specialty; the applicant having another graduate degree; and graduation from a top 40 National Institutes of Health-funded program. Data were analyzed using nonoverlapping 95% confidence intervals. Results The survey was completed by 50 (40%) program directors. Sixty-eight percent of respondents stated a student's ranking would be considered more after USMLE Step 1 scores become P/F, and 60% stated medical schools should share clerkship shelf exam scores with residency programs. There were no significant differences in program directors' rankings of applicant metrics following the transition to P/F Step 1. Conclusion Based on our data, program directors will likely not place a greater emphasis on Step 2 scores, despite it being the only remaining objective measure for all applicants following the switch to a P/F Step 1. Nevertheless, program directors expressed an interest in receiving other objective measures, such as shelf exam scores and class ranking, as part of the application process. Notably, we found no significant changes in the rankings of various applicant metrics before and after the transition to P/F Step 1, indicating that the metrics that were important to program directors prior to the change remain just as critical in the new era of admissions.

Evaluating the impact of pass/fail United States Medical Licensing Examination Step 1 scoring on pathology residency selection.

Beginning 26 January 2022, the United States Medical Licensing Examination Step 1 changed from a numerical score to Pass/Fail. Historically, residency programs have used Step 1 scores as a valuable metric in assessing the competitiveness of applicants. We assessed how residency program criteria will change when evaluating applicants after Step 1 becomes Pass/Fail. A survey was distributed to the program directors of all 144 pathology residency programs accredited by Accreditation Council for Graduate Medical Education. Survey questions evaluated the importance of using Step 1 and Step 2 Clinical Knowledge (CK) scores when assessing applicants. Participants were asked to rank a list of applicant criteria used before and after Step 1 becomes Pass/Fail. Data were analyzed using chi-squared and paired t-tests with significance at P < 0.05. A total of 34 residency program directors (23.6%) responded to the survey. 76.5% (P< 0.001) of responders believed Step 1 scores were able to predict a resident's ability to pass their board exams, while 41.2% believed Step 2 CK could predict a resident's ability to pass board exams and perform clinically in pathology (P = 0.282). 61.8% of responders agreed that an applicant's medical school ranking would become more important (P = 0.001). There were no significant differences in the relative importance of 16 selection criteria after the change of Step 1 to Pass/Fail. It does not appear that Step 2 CK will become more important. Although results are constrained by a 23.6% response rate, it can be a start to guiding future students through residency applications.

Incidence of Emergency Department Presentations of Symptomatic Stone Disease in Pediatric Patients: A Southeastern Study.

Background The incidence of nephrolithiasis during childhood has increased significantly over recent decades. Some studies indicate a rapid rise in adolescents, particularly in African American women. This study serves to identify trends in symptomatic pediatric nephrolithiasis presentations to the emergency department (ED) as a result of increasing incidence and to determine associations between demographic variables at our single-site tertiary pediatric hospital in the Southeast United States. Methods After IRB approval, a review of the data provided by the Pediatric Health Information System, a pediatric database that includes clinical and resource utilization data for 51 of the largest children's hospitals in the nation, yielded 644 pediatric occurrences of nephrolithiasis at single-site emergency departments from 2006 to 2020. The percent change and average percent change in three-year intervals were calculated to establish a trend over time. A chi-square test of independence was performed to assess associations between race, gender, and age groups. Results A total of 780 stone occurrences and associated patient demographic data were reviewed for 644 children (364, 56.52% female) with median age of 183 ± 45.11 months (9-397 months). Of the 644 children, 79 (12.3%) were noted to have recurrent symptomatic nephrolithiasis, contributing to 136/780 stone events. There was a marked increase of 84.4% in confirmed pediatric nephrolithiasis occurrences over 15 years, with an average percent increase of 16.1% every three years. A Chi2 test of independence was performed between gender and age group (>/< 10yr), gender and race, and race and age group. No expected cell frequencies were less than five. There is no statistically significant relationship between gender and age group, χ2 (1, N=644) = 3.30, p=0.692. There is no significant association between race (Caucasian vs. non-Caucasian) and age group (>/< 10yr), χ2 (1, N=644) = 0.393, p=0.531. There is a statistically significant relationship between gender and race (Caucasian vs. non-Caucasian), χ2 (1, N=644) = 5.28, p=0.021. Caucasian females were more likely to present to our tertiary pediatric hospital's emergency department with nephrolithiasis than Caucasian males or non-Caucasian males or females. Additionally, our data reflected a greater percentage of symptomatic nephrolithiasis presentations occurred in the second decade of life (85.4% vs 14.3%, 552 vs 92 stone events). Conclusion Based on our data, there is a marked increase of 84.4% in pediatric nephrolithiasis occurrences from 2006 to 2020, with a mean increase of 16.1% every three years at our single-site tertiary referral pediatric hospital in the Southeast. Among demographic groups, white adolescent females have an increased risk of developing kidney stones.

Effects of prenatal synthetic cannabinoid exposure on the cerebellum of adolescent rat offspring.

Cannabis is the most commonly used illicit drug worldwide. Recently, cannabis use among young pregnant women has greatly increased. However, prenatal cannabinoid exposure leads to long-lasting cognitive, motor, and behavioral deficits in the offspring and alterations in neural circuitry through various mechanisms. Although these effects have been studied in the hippocampus, the effects of prenatal cannabinoid exposure on the cerebellum are not well elucidated. The cerebellum plays an important role in balance and motor control, as well as cognitive functions such as attention, language, and procedural memories. The aim of this study was to investigate the effects of prenatal cannabinoid exposure on the cerebellum of adolescent offspring. Pregnant rats were treated with synthetic cannabinoid agonist WIN55,212-2, and the offspring were evaluated for various cerebellar markers of oxidative stress, mitochondrial function, and apoptosis. Additionally, signaling proteins associated with glutamate dependent synaptic plasticity were examined. Administration of WIN55,212-2 during pregnancy altered markers of oxidative stress by significantly reducing oxidative stress and nitrite content. Mitochondrial Complex I and Complex IV activities were also enhanced following prenatal cannabinoid exposure. With regard to apoptosis, pP38 levels were significantly increased, and proapoptotic factor caspase-3 activity, pERK, and pJNK levels were significantly decreased. CB1R and GluA1 levels remained unchanged; however, GluN2A was significantly reduced. There was a significant decrease in MAO activity although tyrosine hydroxylase activity was unaltered. Our study indicates that the effects of prenatal cannabinoid exposure on the cerebellum are unique compared to other brain regions by enhancing mitochondrial function and promoting neuronal survival. Further studies are required to evaluate the mechanisms by which prenatal cannabinoid exposure alters cerebellar processes and the impact of these alterations on behavior.

Nutraceutical based SIRT3 activators as therapeutic targets in Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, and its incidence is increasing worldwide with increased lifespan. Currently, there is no effective treatment to cure or prevent the progression of AD, which indicates the need to develop novel therapeutic targets and agents. Sirtuins, especially SIRT3, a mitochondrial deacetylase, are NAD-dependent histone deacetylases involved in aging and longevity. Accumulating evidence indicates that SIRT3 dysfunction is strongly associated with pathologies of AD, hence, therapeutic modulation of SIRT3 activity may be a novel application to ameliorate the pathologies of AD. Natural products commonly used in traditional medicine have wide utility and appear to have therapeutic benefits for the treatment of neurodegenerative diseases such as AD. The present review summarizes the currently available natural SIRT3 activators and their potentially neuroprotective molecular mechanisms of action that make them a promising agent in the treatment and management of neurodegenerative diseases such as AD.

Augmented oxidative stress and reduced mitochondrial function in ageing goat testis.

Recently, there is a significant increase in the commercial use of goat products. Nevertheless, there are very few reports on the characterization of redox biomarkers and mitochondrial function in the goat testis. Therefore, in this study we studied the markers of oxidative stress and mitochondrial functions in the goat testis during the process of ageing. Alterations in the markers of oxidative stress/redox biomarkers (contents of reactive oxygen species, nitrite, lipid peroxide, protein carbonyl, glutathione and activities of glutathione peroxidase, monoamine oxidase) and mitochondrial function (Complex-I and Complex-IV activities) were elucidated during the process of ageing. Augmented oxidative stress and decreased mitochondrial function were prominent during ageing in the goat testis. Ageing can lead to induction of oxidative stress and decreased production of ATP; however, the prooxidants generated must be effectively removed from the body by the innate antioxidant defence system to minimize the damage to the host tissue. Conversely, the antioxidants cannot completely scavenge the excessive amount of reactive oxygen species produced during ageing or pathological conditions leading to significant cell death and tissue damage. Thus, the use of effective and potent antioxidants in the feed could significantly reduce oxidative stress and improve mitochondrial function, resulting in enriched goat health.

Elucidating the anti-melanoma effect and mechanisms of Hispolon.

There is a rapid increase in the incidence of melanoma which has led to a global crisis. Thus, there is a great need for developing novel, safe and effective drugs for the treatment of melanoma. Hispolon is a small molecular weight polyphenol derived from Phellinus linteus, which has antioxidant, anti-inflammatory and anti-proliferative activities. Hispolon has been reported to induce apoptosis in gastric cancer, hepatocellular carcinoma, and myeloid leukemia. However, the anticancer effect in melanoma is not well elucidated. Thus, our present study was to investigate the anti-cancer effect of hispolon on melanoma cancer cells. B16BL6 cells were treated with different concentrations of hispolon for 24 h and the effect on oxidative stress, mitochondrial functions, apoptosis and cell proliferation were studied. Hispolon is a potent generator of reactive oxygen species, nitrite and lipid peroxide levels. Furthermore, it significantly inhibits the expression of Bcl-2 and promotes the expression of Bax, increases the activity of caspase 1 and 3, inhibits mitochondrial Complex I and IV activities. By the above mechanisms, hispolon dose-dependently exhibited the antimelanoma effect similar to the well established pharmacological agent, curcumin. Thus, hispolon can be a potent anti-melanoma drug in the future if the pharmacodynamic effects and the toxicological studies are appropriately carried out.

Concurrent nicotine exposure to prenatal alcohol consumption alters the hippocampal and cortical neurotoxicity.

AIMS: This study investigated the neurotoxic effects of prenatal alcohol and nicotine exposure in the cortex and hippocampus of rodents. MAIN METHODS: Behavioral alterations, electrophysiological changes, and biochemical markers associated with cholinergic neurotransmission, neural oxidative stress, mitochondrial function, and apoptosis were evaluated. KEY FINDINGS: Prenatal alcohol exposure induced the generation of ROS, nitrite and lipid peroxide, decreased mitochondrial Complex-I and IV activities, increased Caspase-1 and 3 activities, had no effect on cholinergic neurotransmission, increased expression of PSD-95, decreased LTP and decreased performance on spatial memory tasks. However, nicotine exposure, in addition to alcohol exposure, was found to mitigate the negative effects of alcohol alone on ROS generation and spatial memory task performances. Furthermore, we also studied the role of ILK in prenatal alcohol and nicotine exposure. SIGNIFICANCE: Prenatal Smoking and/or drinking is a major health concern around the world. Thus, our current study may lead to better insights into the molecular mechanisms of fetal alcohol and nicotine exposure on the developing offspring.

Enhanced Bioavailability of Boswellic Acid by Piper longum: A Computational and Pharmacokinetic Study.

Chronic inflammation is a key culprit factor in the onset and progression of several diseases. Novel and pharmacologically effective therapeutic approaches are needed for new treatment remedy or improved pharmacokinetics and pharmacodynamics for existing synthetic drugs, in particular natural products. Boswellic acids are well-known natural products, with capacity to effectively retard inflammation without severe adverse effects. However, the therapeutic use of Boswellic acids are greatly hindered by its poor pharmacokinetic properties. Co-administration strategies that facilitate the oral absorption and distribution of Boswellic acids should lead to a safe and more effective use of this product prophylactically and therapeutically in inflammatory disorders. In this study, we examined the effect of Piper longum extract on the absorption and bioavailability of Boswellic acid in rabbits. In addition, we further explored computational pharmacodynamic interactions between Piper longum and Boswellic acid. Piper longum extract at 2.5 and 10 mg/kg, increased the bioavailability of Boswellic acid (p < 0.05). Based on our drug-based computational modeling, cytochrome P450 (CYP450)-mediated mechanism was involved in increased bioavailability. These findings confirmed that Piper longum with Boswellic acid may be administered orally together for effective therapeutic efficacy. Thus, our studies support the application of Piper longum with Boswellic acid as a novel therapeutic avenue in diseases associated with inflammation.

Dopaminergic neurotoxic effects of 3-TFMPP derivatives.

Designer drugs are synthetically formulated to mimic the psychostimulatory effects of an original controlled/illegal drug of abuse. Designer drugs have similar chemical structure or functional analog as compared to existing controlled psychostimulatory drugs. There is a substantial rise in the production and use of designer drugs globally. Piperazine designer drugs were synthesized as an alternative to MDMA and have shown to induce numerous toxic effects leading to huge health, safety, law enforcement & monetary problems, and lethality. Currently, there are very few studies on the dopaminergic neurotoxicity of 1-(3-trifluoromethylphenyl) piperazine (3-TFMPP) and its derivatives (structural congeners). N27 rat dopaminergic neurons are valid cells to investigate the neurotoxic effects and establish the neurotoxic mechanisms of various substances. In the current study, we studied the time and dose-dependent neurotoxicity mechanisms of dopaminergic neurotoxicity of 3-TFMPP (parent compound) and its derivatives (2-TFMPP, 4-TFMPP). TFMPP derivatives-induced significant neurotoxicity (induced dopaminergic neuronal death. TFMPP derivatives-induced oxidative stress, mitochondrial dysfunction, apoptosis and decreased tyrosine hydroxylase expression. If the use of designer drugs are not strictly regulated and restricted around the world, this can lead to numerous central and peripheral disorders leading to a liability to the current and future society.

Assessment of the cerebellar neurotoxic effects of nicotine in prenatal alcohol exposure in rats.

The adverse effects of prenatal nicotine and alcohol exposure on human reproductive outcomes are a major scientific and public health concern. In the United States, substantial percentage of women (20-25%) of childbearing age currently smoke cigarettes and consume alcohol, and only a small percentage of these individuals quit after learning of their pregnancy. However, there are very few scientific reports on the effect of nicotine in prenatal alcohol exposure on the cerebellum of the offspring. Therefore, this study was conducted to investigate the cerebellar neurotoxic effects of nicotine in a rodent model of Fetal Alcohol Spectrum Disorder (FASD). In this study, we evaluated the behavioral changes, biochemical markers of oxidative stress and apoptosis, mitochondrial functions and the molecular mechanisms associated with nicotine in prenatal alcohol exposure on the cerebellum. Prenatal nicotine and alcohol exposure induced oxidative stress, did not affect the mitochondrial functions, increased the monoamine oxidase activity, increased caspase expression and decreased ILK, PSD-95 and GLUR1 expression without affecting the GSK-3ß. Thus, our current study of prenatal alcohol and nicotine exposure on cerebellar neurotoxicity may lead to new scientific perceptions and novel and suitable therapeutic actions in the future.