Seizure-Induced Cardiomyopathy: A Case of Takotsubo Cardiomyopathy Following an Epileptic Event.

We present a case, written with the assistance of the Chat Generative Pre-training Transformer (ChatGPT) Artificial Intelligence (AI), of a 75-year-old female with a history of hypertension, epilepsy, coronary artery disease, and alcohol use disorder. She presented with a tonic-clonic seizure, tachycardia, and a cyanotic right hand. Diagnostic tests revealed stress-induced cardiomyopathy, patent bilateral subclavian and axillary arteries with heavy calcification of bilateral upper extremity arteries, and a small filling defect in the segmental branch of the left lower lobe. The patient was started on antiepileptic medication, thiamine/folate, and heparin drip for limb ischemia. Despite treatment with multiple anti-arrhythmic agents, the patient developed cardiogenic shock and underwent left heart catheterization with Impella placement. The Impella was removed 72 hours after placement, and the patient was started on low-dose Milrinone and Levophed for hemodynamic support. The patient eventually recovered and was discharged to long-term acute care.

Not Another Pleural Effusion: A Unique Case of Metastatic Endometrial Stromal Sarcoma.

The etiology of complicated pleural effusion can be vast. We present a unique case of an unsuspected metastatic endometrial stromal sarcoma (ESS) in an asymptomatic patient with an incidentally found complicated pleural effusion. A 69-year-old female with no pertinent past medical history was referred to pulmonology for an effusion noted on a routine chest X-ray. Her surgical history was significant for a hysterectomy. At the time of evaluation in the pulmonology clinic, the patient was asymptomatic with stable vital signs. Computed tomography of her chest showed a complex pleural effusion which was drained by cardiothoracic surgery. Fluid analysis results were positive for estrogen and progesterone receptor-positive mesenchymal tumor. Follow-up imaging was negative for any other metastasis. Appropriate management and drainage of this asymptomatic pleural effusion resulted in the diagnosis of a rare malignancy. Given the good clinical prognosis of mesenchymal tumors, the patient was appropriately treated and doing well. We present the case of a patient who was found to have a rare malignancy rather than a benign chronic pleural effusion, as previously suspected. This neoplasm represented a metastatic ESS, especially in this patient's setting of a hysterectomy.

Glucocorticoid Therapy in COVID-19-Induced Organizing Pneumonia: A Rare Occurrence.

Background Although the incidence of post-COVID-19 organizing pneumonia (OP) is low, the mortality and morbidity in select patients appear to be high. Anticipating specific populations who may be at higher risk and initiating treatment earlier could reduce mortality. Research question Does treatment with high dose, standard dose, or no glucocorticoids for COVID-19 infection impact the incidence and clinical outcome in COVID-19-induced OP? Study design and methods This was a single-center, retrospective, observational cohort study conducted from 03/01/2020 to 06/30/2021 in hospitalized patients over the age of 18 with confirmed COVID-19 infection and computed tomography (CT) scan evidence of OP. Institutional review board (IRB) approval was obtained from the institution (STUDY00002241). Patients' demographics and oxygen requirements at the time of diagnosis, at the time of discharge, and at one, three, six, 10, and 12 months post-discharge were obtained. The dose, duration, and choice of glucocorticoid therapy were recorded for each subject, as well as oxygen requirements during hospitalization. Despite radiological evidence of OP, patients on minimal supplemental oxygen requirements did not receive high-dose or long-duration glucocorticoid therapy. Results A total of 881 patients were admitted with COVID-19, of which 42 met the study criteria. Three patients underwent a lung biopsy to confirm the diagnosis of organizing pneumonia. All other patients were diagnosed based on CT imaging and clinical presentation. Of the patients, 17% did not receive any steroid treatment, while 36% received dexamethasone and 43% received prednisone. The most common oxygen requirement at the time of discharge for steroid-treated patients was nasal cannula (55%) and room air (29%). The incidence of OP in this patient population was 0.05 with a mortality rate of 14%. Interpretation and relevance The incidence of post-COVID-19 OP appears to be lower than anticipated. Steroids for patients on lower supplemental oxygen requirements were discontinued although they had radiological evidence of OP. Patients who were on higher supplemental oxygen requirements at 10 days were continued on steroids regardless of imaging. The decision to continue steroids should be based on individual patient characteristics such as oxygen requirements. In the future, larger multicenter cohort studies would help understand further treatment of post-COVID-19-associated OP. Anticipating specific populations who may be at higher risk and starting treatment earlier could help reduce mortality.

Rationale and design of GENEiUS: a prospective observational study on the genetic and environmental determinants of body mass index evolution in Canadian undergraduate students.

INTRODUCTION: Obesity is a global epidemic and is a risk factor for developing other comorbidities. Young adulthood is a critical period for body weight change and establishing healthy lifestyle behaviours. The 'Freshman 15' suggests that undergraduate students gain 15 lbs (6.8 kg) during their first year of university, although evidence estimates a more modest weight gain of approximately 3-5 lbs (1.4-2.3 kg). Previous studies have only investigated weight change in the first year and do not study potential risk factors. Genetic and EnviroNmental Effects on weight in University Students (GENEiUS) is a prospective observational study which will investigate the environmental and biological determinants of weight change in undergraduate students over 4 years. METHODS AND ANALYSIS: The GENEiUS study will recruit 2500 multiethnic undergraduates aged 17-25 years at McMaster University at the start of their first year and will follow them every 6 months for 4 years. Primary outcomes are obesity traits: body mass index, waist circumference, waist-to-hip ratio, body fat mass and body fat percentage. The contribution of well-established and novel genetic variants for obesity traits and heritability values will be derived from whole-genome single-nucleotide polymorphism genotyping arrays. Civil status, age, sex, ethnicity, length of residence in Canada, religiosity, energy intake, physical activity, exercise motivation, electronic screen time, sleep patterns, history of assault, smoking status, alcohol consumption, medication and drug use, stress, impulsivity, body image perception, self-esteem, anxiety, eating disorders and depression will be investigated for their effect on obesity traits. The findings of the GENEiUS study will be used to help design obesity prevention programme in North American universities with multiethnic populations. ETHICS AND DISSEMINATION: Ethical approval of the study protocol has been obtained from the Hamilton Integrated Research Ethics Board. Study results will be disseminated through scientific publications, scholarly meetings, and collaborative meetings with university administration and student groups.

Evaluating the transferability of 15 European-derived fasting plasma glucose SNPs in Mexican children and adolescents.

Genome wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) that are associated with fasting plasma glucose (FPG) in adult European populations. The contribution of these SNPs to FPG in non-Europeans and children is unclear. We studied the association of 15 GWAS SNPs and a genotype score (GS) with FPG and 7 metabolic traits in 1,421 Mexican children and adolescents from Mexico City. Genotyping of the 15 SNPs was performed using TaqMan Open Array. We used multivariate linear regression models adjusted for age, sex, body mass index standard deviation score, and recruitment center. We identified significant associations between 3 SNPs (G6PC2 (rs560887), GCKR (rs1260326), MTNR1B (rs10830963)), the GS and FPG level. The FPG risk alleles of 11 out of the 15 SNPs (73.3%) displayed significant or non-significant beta values for FPG directionally consistent with those reported in adult European GWAS. The risk allele frequencies for 11 of 15 (73.3%) SNPs differed significantly in Mexican children and adolescents compared to European adults from the 1000G Project, but no significant enrichment in FPG risk alleles was observed in the Mexican population. Our data support a partial transferability of European GWAS FPG association signals in children and adolescents from the admixed Mexican population.

Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity.

In high-, middle- and low-income countries, the rising prevalence of obesity is the underlying cause of numerous health complications and increased mortality. Being a complex and heritable disorder, obesity results from the interplay between genetic susceptibility, epigenetics, metagenomics and the environment. Attempts at understanding the genetic basis of obesity have identified numerous genes associated with syndromic monogenic, non-syndromic monogenic, oligogenic and polygenic obesity. The genetics of leanness are also considered relevant as it mirrors some of obesity's aetiologies. In this report, we summarize ten genetically elucidated obesity syndromes, some of which are involved in ciliary functioning. We comprehensively review 11 monogenic obesity genes identified to date and their role in energy maintenance as part of the leptin-melanocortin pathway. With the emergence of genome-wide association studies over the last decade, 227 genetic variants involved in different biological pathways (central nervous system, food sensing and digestion, adipocyte differentiation, insulin signalling, lipid metabolism, muscle and liver biology, gut microbiota) have been associated with polygenic obesity. Advances in obligatory and facilitated epigenetic variation, and gene-environment interaction studies have partly accounted for the missing heritability of obesity and provided additional insight into its aetiology. The role of gut microbiota in obesity pathophysiology, as well as the 12 genes associated with lipodystrophies is discussed. Furthermore, in an attempt to improve future studies and merge the gap between research and clinical practice, we provide suggestions on how high-throughput '-omic' data can be integrated in order to get closer to the new age of personalized medicine.

Obesity genetics in mouse and human: back and forth, and back again.

Obesity is a major public health concern. This condition results from a constant and complex interplay between predisposing genes and environmental stimuli. Current attempts to manage obesity have been moderately effective and a better understanding of the etiology of obesity is required for the development of more successful and personalized prevention and treatment options. To that effect, mouse models have been an essential tool in expanding our understanding of obesity, due to the availability of their complete genome sequence, genetically identified and defined strains, various tools for genetic manipulation and the accessibility of target tissues for obesity that are not easily attainable from humans. Our knowledge of monogenic obesity in humans greatly benefited from the mouse obesity genetics field. Genes underlying highly penetrant forms of monogenic obesity are part of the leptin-melanocortin pathway in the hypothalamus. Recently, hypothesis-generating genome-wide association studies for polygenic obesity traits in humans have led to the identification of 119 common gene variants with modest effect, most of them having an unknown function. These discoveries have led to novel animal models and have illuminated new biologic pathways. Integrated mouse-human genetic approaches have firmly established new obesity candidate genes. Innovative strategies recently developed by scientists are described in this review to accelerate the identification of causal genes and deepen our understanding of obesity etiology. An exhaustive dissection of the molecular roots of obesity may ultimately help to tackle the growing obesity epidemic worldwide.

Angiogenesis in the placenta: the role of reactive oxygen species signaling.

Proper placental development and function are central to the health of both the mother and the fetus during pregnancy. A critical component of healthy placental function is the proper development of its vascular network. Poor vascularization of the placenta can lead to fetal growth restriction, preeclampsia, and in some cases fetal death. Therefore, understanding the mechanisms by which uterine stressors influence the development of the placental vasculature and contribute to placental dysfunction is of central importance to ensuring a healthy pregnancy. In this review we discuss how oxidative stress observed in maternal smoking, maternal obesity, and preeclampsia has been associated with aberrant angiogenesis and placental dysfunction resulting in adverse pregnancy outcomes. We also highlight that oxidative stress can influence the expression of a number of transcription factors important in mediating angiogenesis. Therefore, understanding how oxidative stress affects redox-sensitive transcription factors within the placenta may elucidate potential therapeutic targets for correcting abnormal placental angiogenesis and function.