The precise orchestration of hormonal regulation at all levels of the hypothalamic-pituitary-gonadal axis is essential for normal reproductive function and fertility. The pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) stimulates the synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by pituitary gonadotropes. GnRH acts by binding to its high affinity seven-transmembrane receptor (GnRHR) on the cell surface of anterior pituitary gonadotropes. Different signaling cascades and transcriptional mechanisms are activated, depending on the variation in GnRH pulse frequency, to stimulate the synthesis and release of FSH and LH. While changes in GnRH pulse frequency may explain some of the differential regulation of FSH and LH, other factors, such as activin, inhibin and sex steroids, also contribute to gonadotropin production. In this review, we focus on the transcriptional regulation of the gonadotropin subunit genes and the signaling pathways activated by pulsatile GnRH.

Human pesticide exposure can occur both occupationally and environmentally during manufacture and after the application of indoor and outdoor pesticides, as well as through consumption via residues in food and water. There is evidence from experimental studies that numerous pesticides, either in isolation or in combination, act as endocrine disruptors, neurodevelopmental toxicants, immunotoxicants, and carcinogens. We reviewed the international literature on this subject for the years between 1990 and 2017. The studies were considered in this review through MEDLINE and WHO resources. Out of the n = 1817 studies identified, n = 94 were reviewed because they fulfilled criteria of validity and addressed associations of interest. Epidemiological studies have provided limited evidence linking pre- and post-natal exposure to pesticides with cancers in childhood, neurological deficits, fetal death, intrauterine growth restriction, preterm birth, and congenital abnormalities (CAs). In this review, the potential association between pesticide exposure and the appearance of some human CAs (including among others musculoskeletal abnormalities; neural tube defects; urogenital and cardiovascular abnormalities) was investigated. A trend towards a positive association between environmental or occupational exposure to some pesticides and some CAs was detected, but this association remains to be substantiated. Main limitations of the review include inadequate exposure assessment and limited sample size. Adequately powered studies with precise exposure assessments such as biomonitoring, are warranted to clarify with certainty the potential association between pesticide exposure and human CAs.

Summary Background Despite reports of fungal infections in patients with inflammatory bowel disease (IBD), their clinical and microbiological characteristics remain unknown. Objectives The aim of this systematic review was to examine all available evidence regarding fungal infections in patients with IBD. Methods Systematic search of PubMed (through 27 May 2017) for studies providing data on clinical, microbiological, treatment and outcome data of fungal infections in patients with IBD. The primary study outcome was to record the most common fungal species in patients with IBD. Secondary outcomes were classified into 3 categories: (i) characteristics of fungal infections; (ii) data on IBD and (iii) treatment and outcomes of fungal infections in patients with IBD. Results Fourteen studies with data on 1524 patients were included in final analysis. The most common fungal infections in patients with IBD were caused by Candida species (903 infections); the most commonly reported site of Candida infection was the gastrointestinal tract. Available evidence shows that most fungal infections occur within 12 months of IBD treatment and within 6 months when anti-TNFa agents are used. Conclusions This systematic review thoroughly describes fungal infections in patients with IBD and provides important information for the early detection and management of these infections.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 19 , is a novel human Coronavirus that is responsible for about 300,000 deaths worldwide. To date, there is no confirmed treatment or vaccine prevention strategy against COVID-19. Due to the urgent need for effective treatment, drug repurposing is regarded as the immediate option. Potential drugs can often be identified via in silico drug screening experiments. Consequently, there has been an explosion of in silico experiments to find drug candidates or investigate anecdotal claims. One drug with several anecdotal accounts of benefit is Cefuroxime. The aim of this study was to identify and summarize in silico evidence for possible activity of Cefuroxime against SARS-CoV-2.To this end, we performed a scoping review of literature of in silico drug repurposing experiments for SARS-CoV-2 using PRISMA-ScR. We searched Medline, Embase, Scopus, Web of Knowledge, and Google Scholar for original studies published between 1st Feb, 2020 and 15th May, 2020 that screened drug libraries, and identified Cefuroxime as a top-ranked potential inhibitor drug against SARS-CoV-2 proteins. Six studies were identified. These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex. We provided a summary of the methodology and findings of the identified studies. Our scoping review identified significant in silico evidence that Cefuroxime may be a potential multitarget inhibitor of SARS-CoV-2. Further in vitro and in vivo studies are required to evaluate the potential of Cefuroxime for COVID-19.

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Objective: To demonstrate important points regarding the possible hypoglycemic effects of sulfasalazine and suggest possible underlying mechanism(s) accounting for sulfasalazine-induced hypoglycemia. Methods: We describe a case of reversible sulfasalazine-induced hypoglycemia, review the literature, and discuss a potential mechanism accounting for sulfasalazine-induced hypoglycemia. Results: A 63-year-old man with Crohn disease treated with sulfasalazine and type 2 diabetes complicated by endstage renal disease was admitted for treatment of persistent hypoglycemia. Insulinoma was initially suspected, but localization studies including endoscopic ultrasound were negative. This raised the possibility of sulfasalazineinduced hypoglycemia. Three days after sulfasalazine was stopped, he became normoglycemic. Hypoglycemia has not recurred since discontinuing sulfasalazine. Conclusion: Clinicians should be aware of the potential hypoglycemic effect of sulfasalazine. Doses should be reduced in patients with impaired renal function, and it should be discontinued if otherwise unexplained hypoglycemia develops.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i’s) are the newest class of anti-hyperglycemic drugs. Their mechanism of action involves increasing urinary glucose excretion by preventing glucose reabsorption in the proximal renal tubules, yet they can also promote ketogenesis under certain circumstances. Numerous reports suggest an association between SGLT2i’s and diabetic ketoacidosis (DKA), but the medical literature remains sparse. Since the use of these drugs for diabetes has increased dramatically due to favorable cardiac outcomes, identification of patients at greatest risk for this life-threatening complication is essential. Therefore, in an effort to better understand the circumstances in which SGLT2i associated DKA occurs we reviewed all available cases at our hospital over a 5-year period. Patients and Methods: We retrospectively reviewed all cases of ketoacidosis associated with SGLT2i use at our hospital from 2013 to October 2018 using an electronic medical record search algorithm. Terms included canagliflozin, dapagliflozin, empagliflozin, SGLT2 inhibitors, metabolic acidosis, ketoacidosis, diabetes, and DKA. Patients that developed DKA without being treated with SGLT2i were excluded. Results: We identified 77 cases, 21 of which met criteria for DKA associated with SGLTi use. 64% were female and 36% were male, average age was 57.8 years, BMI 29.8 kg/m 2 , and mean diabetes duration was 11 years. The majority carried diagnoses of T2DM (94%) and 83.4% had no history of DKA prior to using an SGLT2i. The most common presenting symptoms were nausea, vomiting (38%), abdominal pain (28.5%) and altered mental status (19%). Common precipitants were poor oral intake (57.14%) and infection (23.8%). Average blood glucose concentrations at presentation were 329 + 36 mg/dl, interestingly, 52% of the episodes were euglycemic DKA (euDKA) with blood glucose <300 mg/dl. Average anion gap values were 25+1.4 mg/dl, bicarbonate 12.6+1.3 mg/dl and pH 7.17+0.03. All had positive urine ketones and average beta-hydroxybutyrate levels were 6.4 mmol/l. Latest hemoglobin A1c was 9.8+0.6%. A variety of drugs were prescribed along with an SGLT2i, and 62% of patients were using insulin. SGLT2i’s associated with DKA were canagliflozin (52%), empagliflozin (29%), and dapagliflozin (19%). No cases were fatal. Conclusion: We found that the majority of SGLT2i associated DKA cases occurred in older patients with type 2 DM without prior episodes of DKA. The most common presenting symptoms were nausea, vomiting, abdominal pain and altered mental status, while poor food intake and infection where the main precipitants. Clinicians should consider the possibility of ketoacidosis in SGLT2i-treated patients presenting with these symptoms, even in absence of marked hyperglycemia. If DKA is diagnosed, the SGLT2i should be discontinued and insulin therapy for DKA should be initiated.