Future Perspective: Harnessing the Power of Artificial Intelligence in the Generation of New Peptide Drugs.

The expansive field of drug discovery is continually seeking innovative approaches to identify and develop novel peptide-based therapeutics. With the advent of artificial intelligence (AI), there has been a transformative shift in the generation of new peptide drugs. AI offers a range of computational tools and algorithms that enables researchers to accelerate the therapeutic peptide pipeline.

Effects of a high cholesterol diet on chill tolerance are highly context-dependent in Drosophila.

Chill susceptible insects are thought to be injured through different mechanisms depending on the duration and severity of chilling. While chronic chilling causes "indirect" injury through disruption of metabolic and ion homeostasis, acute chilling is suspected to cause "direct" injury, in part through phase transitions of cell membrane lipids. Dietary supplementation of cholesterol can reduce acute chilling injury in Drosophila melanogaster (Shreve et al.

Patterns of Prescription Medication Use during the First Trimester of Pregnancy in the United States, 1997-2018.

The objective of this analysis was to describe patterns of prescription medication use during pregnancy, including secular trends, with consideration of indication, and distributions of use within demographic subgroups. We conducted a descriptive secondary analysis using data from 9,755 women whose infants served as controls in two large United States case-control studies from 1997-2011 and 2014-2018. After excluding vitamin, herbal, mineral, vaccine, i.

Photodistributed Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and proposal for a new diagnostic classification.

Background: Ultraviolet radiation (UVR) exposure is commonly reported as a risk factor for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, minimal evaluation of photo-induced SJS/TEN has been conducted. Thus, this review identifies all cases of SJS/TEN that are linked to an acute exposure of UVR and outlines the unifying characteristics of these cases.

Mental health and sleep habits during preclinical years of medical school.

Objectives: The purpose of this non interventional study was to define changes in anxiety, depression, and sleep quality of medical students in their first two years of medical school while considering potential risk factors of self-reported chronic disease, sleep quantity, year of medical school and exercise habits. Since this study was ongoing during the COVID-19 pandemic, its effect was also evaluated.

Participants: /METHODS: A cohort of 197 medical students was evaluated longitudinally using survey methods to quantify changes from pre-medical school and summer break to each semester in medical school throughout years one and two.

Use of vasoactive medications in pregnancy and the risk of stillbirth among birth defect cases.

Background: Many previous studies have identified risk factors for stillbirth, but few examine stillbirth among pregnancies affected with birth defects. Because many hypothesized etiologies of stillbirth work through vascular pathologies of the placenta, we examined maternal use of vasoactive medications in relation to stillbirth among pregnancies affected with birth defects.

Methods: Data were analyzed from the National Birth Defects Prevention Study (1997-2011).

Periconceptional nonsteroidal anti-inflammatory drug use, folic acid intake, and the risk of spina bifida.

Background: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy may increase risk for neural tube defects (NTDs), including spina bifida. Folic acid intake can prevent NTDs, but it is not known whether it modifies any risks associated with NSAID use.

Objectives: To assess the impact of periconceptional NSAID use on the risk of spina bifida overall and stratified by folic acid intake.

Multimodality assessment of heart failure with preserved ejection fraction skeletal muscle reveals differences in the machinery of energy fuel metabolism.

Aims: Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants.

Methods And Results: Fifty-nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal-effort cardiopulmonary exercise test to define peak oxygen consumption (VO ), ventilatory threshold (VT), and VO efficiency (ratio of total work performed to O consumed).

Progression-Mediated Changes in Mitochondrial Morphology Promotes Adaptation to Hypoxic Peritoneal Conditions in Serous Ovarian Cancer.

Ovarian cancer is the deadliest gynecological cancer in women, with a survival rate of less than 30% when the cancer has spread throughout the peritoneal cavity. Aggregation of cancer cells increases their viability and metastatic potential; however, there are limited studies that correlate these functional changes to specific phenotypic alterations. In this study, we investigated changes in mitochondrial morphology and dynamics during malignant transition using our MOSE cell model for progressive serous ovarian cancer.

Folic acid antagonist use before and during pregnancy and risk for selected birth defects.

Background: Maternal folic acid (FA) intake before and during early pregnancy reduces the risk for neural tube defects (NTDs); evidence suggests it may also reduce the risk for oral clefts, urinary defects, and cardiac defects. We sought to re-examine the use of drugs, which affect folate metabolism, dihydrofolate reductase inhibiting (DHFRI) medications, and anti-epileptic drugs (AEDs), in data collected in the post-FA fortification era (1998+) in the Slone Birth Defects Study.

Methods: We assessed maternal DHFRI and AED use and risk for NTDs, oral clefts, and urinary and cardiac defects.

Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects.

Importance: Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks.

Objective: To examine associations between individual antidepressants and specific birth defects with and without attempts to partially account for potential confounding by underlying conditions.

Design, Setting, And Participants: The population-based, multicenter case-control National Birth Defects Prevention Study (October 1997-December 2011) included cases with selected birth defects who were identified from surveillance systems; controls were randomly sampled live-born infants without major birth defects.

The cardiolipin-binding peptide elamipretide mitigates fragmentation of cristae networks following cardiac ischemia reperfusion in rats.

Mitochondrial dysfunction contributes to cardiac pathologies. Barriers to new therapies include an incomplete understanding of underlying molecular culprits and a lack of effective mitochondria-targeted medicines. Here, we test the hypothesis that the cardiolipin-binding peptide elamipretide, a clinical-stage compound under investigation for diseases of mitochondrial dysfunction, mitigates impairments in mitochondrial structure-function observed after rat cardiac ischemia-reperfusion.

Trends in first-trimester nausea and vomiting of pregnancy and use of select treatments: Findings from the National Birth Defects Prevention Study.

Background: Although nausea and vomiting of pregnancy (NVP) is common, the secular and demographic trends of NVP and its treatments are not well-studied.

Objectives: To describe the prevalence and patterns of first-trimester NVP and selected treatments among controls in the National Birth Defects Prevention Study (NBDPS).

Methods: National Birth Defects Prevention Study is a population-based case-control study of birth defects in the United States (1997-2011).

Safety of drug use in patients with a primary mitochondrial disease: An international Delphi-based consensus.

Clinical guidance is often sought when prescribing drugs for patients with primary mitochondrial disease. Theoretical considerations concerning drug safety in patients with mitochondrial disease may lead to unnecessary withholding of a drug in a situation of clinical need. The aim of this study was to develop consensus on safe medication use in patients with a primary mitochondrial disease.

Tetanus, diphtheria, and pertussis vaccine (Tdap) in pregnancy and risk of major birth defects in the offspring.

Background: The tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is recommended during pregnancy to protect newborns against pertussis infection in the months prior to their primary pertussis vaccination. Although research on the safety of the vaccine has been reassuring, most previous studies have considered major malformations as a single outcome, and have not examined potential risks for specific malformations.

Methods: Using data from the Slone Epidemiology Center Birth Defects Study collected between 2006 and 2015, we identified exposures to Tdap vaccine in both early and late pregnancy and examined potential risks for specific malformations.

Risk of Stillbirth for Fetuses With Specific Birth Defects.

Objective: To estimate the risk of stillbirth (fetal death at 20 weeks of gestation or more) associated with specific birth defects.

Methods: We identified a population-based retrospective cohort of neonates and fetuses with selected major birth defects and without known or strongly suspected chromosomal or single-gene disorders from active birth defects surveillance programs in nine states. Abstracted medical records were reviewed by clinical geneticists to confirm and classify all birth defects and birth defect patterns.

Cardioprotective effects of idebenone do not involve ROS scavenging: Evidence for mitochondrial complex I bypass in ischemia/reperfusion injury.

Novel therapeutic strategies to treat mitochondrial deficiencies in acute coronary syndromes are needed. Complex I of the mitochondrial electron transport system is damaged following ischemia/reperfusion (I/R) injury. This disruption contributes to aberrant electron transport, diminished bioenergetics, an altered redox environment, and mitochondrial damage involved in tissue injury.

Periconceptional folic acid and risk for neural tube defects among higher risk pregnancies.

Background: Women with a previous neural tube defect (NTD)-affected pregnancy are recommended to consume 4,000 μg daily folic acid (FA) for prevention (10 times the general-population recommendation). Protection from doses between 400 and 4,000 μg for this and other higher risk groups is unclear.

Methods: In the case-control Slone Birth Defects Study (1988-2015), we examined the associations between periconceptional FA doses and NTDs among four higher risk groups: NTD family history, periconceptional antiepileptic drug exposure (AED), pregestational diabetes, and prepregnancy obesity.

Oseltamivir exposure in pregnancy and the risk of specific birth defects.

Background: Influenza during pregnancy contributes to maternal morbidity and mortality. Neuraminidase inhibitors, including oseltamivir, are recommended for treating women with influenza during pregnancy.

Methods: Data from the Slone Birth Defects Study from 2009 to 2015 were used to investigate associations between oseltamivir and specific birth defects.

One-Carbon Cofactor Intake and Risk of Neural Tube Defects Among Women Who Meet Folic Acid Recommendations: A Multicenter Case-Control Study.

We aimed to investigate associations between individual and concurrent (≥2) intakes of one-carbon cofactors vitamins B6 and B12, choline, betaine, and methionine and neural tube defect (NTD) outcomes among mothers meeting the folic acid recommendations. In the Slone Birth Defects Study (case-control design; North America, 1998-2015), mothers of 164 NTD cases and 2,831 nonmalformed controls completed food frequency questionnaires and structured interviews. Estimated intakes of one-carbon cofactors were dichotomized (high vs.

Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997-2011.

Background: Benzodiazepine medications can be used to treat anxiety, a condition affecting 15% of women of childbearing age in the United States. Studies have shown conflicting results for the association between benzodiazepine use during pregnancy and birth defects.

Methods: We analyzed 1997-2011 data from the National Birth Defects Prevention Study, a multisite, population-based case-control study.

Risk factors for congenital microcephaly in the pre-Zika era.

Background: The Zika epidemic has brought increased attention to congenital microcephaly as a birth outcome. However, little is known about risks for microcephaly unrelated to Zika.

Methods: Using data from the Slone Epidemiology Center Birth Defects Study from 1993 to 2015, we identified 57 cases of microcephaly alone ("isolated") and 109 cases of microcephaly that included other major birth defects ("non-isolated"), and considered a large number of potential risk factors including demographic characteristics, illnesses, and medications used during pregnancy.