Azithromycin Treatment for Acne Vulgaris: A Case Report on the Risk of Clostridioides difficile Infection.

BACKGROUND Clostridium difficile (C. difficile) is a gram-positive, anaerobic, spore-forming bacillus. It can lead to pseudomembranous colitis characterized by electrolyte disturbances, toxic megacolon, and septic shock. The risk of C. difficile infection is higher with use of certain classes of antibiotics, or when an antibiotic used for a long time. Azithromycin is a macrolide antibiotic known to be safe, with few adverse effects such as diarrhea, stomach pain, and constipation. Azithromycin is currently used for the treatment of acne, with different dosing regimens for patients who cannot receive traditional treatment based on practice guidelines. CASE REPORT A 41-year-old woman was treated with a course of azithromycin 500 mg by mouth 3 times weekly for 6 weeks for acne vulgaris. This was her second antibiotic course of acne treatment within 10 months. A few days after completion of the second azithromycin course, she presented to the clinic with worsening abdominal pain and frequent soft bloody stool. A complete blood count test, C. difficile toxin test, stool culture, and colonoscopy were ordered. She was diagnosed with C. difficile infection confirmed by C. difficile toxin and symptoms. CONCLUSIONS Despite the safety profile of azithromycin, our patient was predisposed to a non-severe case of C. difficile-associated diarrhea, most likely due to the repeated course of the azithromycin regimen that was used to treat her acne vulgaris. This report highlights the importance of managing patients with acne vulgaris according to current practice guidelines, and to report a link between the use of azithromycin as an acne treatment and the occurrence of C. difficile colitis.

Severe Neutropenia and Hepatotoxicity After Carbimazole Drug Therapy for Hyperthyroidism in a Pediatric Patient: A Case Report.

BACKGROUND Hyperthyroidism is an overproduction of thyroid hormones. Carbimazole is an anti-thyroid medication used to treat hyperthyroidism in adults and children. It is a thionamide associated with rare adverse effects such as neutropenia, leukopenia, agranulocytosis, and hepatotoxicity. Severe neutropenia is a life-threatening event characterized by a sharp drop in absolute neutrophil count. Severe neutropenia can be treated by discontinuation of the precipitating medication. Administration of granulocyte colony-stimulating factor provides longer protection against neutropenia. Elevated liver enzymes indicate hepatotoxicity, which usually normalize after discontinuation of the offending medication. CASE REPORT A 17-year-old girl was treated with carbimazole since the age of 15 for hyperthyroidism secondary to Graves' disease. She initially received 10 mg of carbimazole orally twice daily. After 3 months, the patient's thyroid function reflected residual hyperthyroidism and was then up-titrated to 15 mg orally in the morning and 10 mg orally in the evening. She presented to the emergency department reporting fever, body aches, headache, nausea, and abdominal pain for 3 days. She was diagnosed with severe neutropenia and hepatotoxicity induced by carbimazole after 18 months of dose modification. CONCLUSIONS In hyperthyroidism, it is important to maintain patients in a euthyroid state for a long period to minimize the autoimmunity and hyperthyroid relapse, which often requires long-term use of carbimazole. However, severe neutropenia and hepatotoxicity are rare and serious adverse effects of carbimazole. Clinicians should be aware of the importance to discontinuation of carbimazole, administration of granulocyte colony-stimulating factors, and supportive treatment to reverse the consequences.

Students engagement using polls in virtual sessions of physiology, pathology, and pharmacology at King Saud bin Abdulaziz University for Health Sciences during COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Active involvement of students in class using technology is associated with effective learning and understanding. This work intended to analyze the impact of interactive teaching on medical students' engagement, learning, performance, understanding and attendance in virtual classes of physiology, pathology, and pharmacology during COVID-19 pandemic. METHODS: A descriptive cross-sectional study was carried out at college of medicine at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) in Riyadh during January-April 2022. Third- and fourth-year medical students filled a self-reported questionnaire that assessed students' engagement, understanding, performance, and attendance during the sessions of three courses within the curriculum. The Chi-square test or Fisher's exact test was used to compare the difference between the survey responses. RESULTS: A total of 184/234 questionnaires were completed and returned, with an overall response rate of 78.6%. Fifty-five percent of the participants were involved at least more than 5 times in polls during the class. Majority (86.9%), of the students agreed on enjoying participation in polls during the class, and 88.9% recommended the utilization of the polls again. Participation in polls improved understanding and performance of 88%, and 63% of students respectively. In addition, 38% were neutral regarding attendance improvement and spending more time for the class. Around 53% students agreed that polls improved their grades. CONCLUSION: In conclusion, this study showed that there is an impact of using interactive polls in virtual classes in medical students at KSAU-HS. It is recommended to continue using polls in all subjects in on-site sessions. This will be a great preface step toward switching the traditional teaching to the interactive teaching using flipped classroom strategy in the future.

Molecular mechanisms underlying some major common risk factors of stroke.

Ischemic and hemorrhagic strokes are the most common known cerebrovascular disease which can be induced by modifiable and non-modifiable risk factors. Age and race are the most common non-modifiable risk factors of stroke. However, hypertension, diabetes, obesity, dyslipidemia, physical inactivity, and cardiovascular disorders are major modifiable risk factors. Understanding the molecular mechanism mediating each of these risk factors is expected to contribute significantly to reducing the risk of stroke, preventing neural damage, enhancing rehabilitation, and designing suitable treatments. Abnormalities in the structure of the blood-brain barrier and blood vessels, thrombosis, vasoconstriction, atherosclerosis, reduced cerebral blood flow, neural oxidative stress, inflammation, and apoptosis, impaired synaptic transmission, excitotoxicity, altered expression/activities of many channels and signaling proteins are the most knows mechanisms responsible for stroke induction. However, the molecular role of risk factors in each of these mechanisms is not well understood and requires a lot of search and reading. This review was designed to provide the reader with a single source of information that discusses the current update of the prevalence, pathophysiology, and all possible molecular mechanisms underlying some major risk factors of stroke namely, hypertension, diabetes mellitus, dyslipidemia, and lipid fraction, and physical inactivity. This provides a full resource for understanding the molecular effect of each of these risk factors in stroke.

Do Parental Comorbidities Affect the Severity of Autism Spectrum Disorder?

Background Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by defective social communication and interaction with a repetitive pattern of monotonous or stereotyped behavior. Although the exact etiology of ASD is unknown, many factors may be implicated in the development of ASD. We aimed to determine the correlation between specific parental factors and Autism Treatment Evaluation Checklist (ATEC) scores. Methods This cross-sectional study was conducted at the Prince Nasser Bin Abdulaziz Center for Autism, Autism Center for Excellence, and Academy of Special Education for Autism in Riyadh, Saudi Arabia. We enrolled children diagnosed with ASD and their parents from these centers. Data were collected through self-administered questionnaires to the patients' parents. Results All included children were <18 years old. In total, 71 (92.2%) children were male and six (7.8%) were female. Further, 77 (100%) patients were diagnosed with autistic disorder. Children of consanguineous parents, underweight mothers and obese fathers, mothers with a history of depression during pregnancy, and mothers aged ≥31 years during pregnancy tend to have a higher mean ATEC score. The health domain was the most significantly correlated with ATEC scores, with a Pearson correlation of 0.880. In linear regression analysis, only maternal depression during pregnancy was significantly correlated with ATEC scores. Conclusion Our patients had a mean ATEC score of 86.2. The health domain was the most significantly correlated with ATEC scores, with a Pearson correlation of 0.880. Linear regression analysis revealed that consanguinity, parental chronic disease, parental allergy, smoking, drug use during pregnancy, paternal and maternal body mass index (BMI), and sibling number were not significantly correlated with ATEC scores (P=0.701, 0.693, 0.133, 0.874, 0.982, 0.255, 0.778, and 0.502, respectively). However, maternal depression during pregnancy was significantly correlated with ATEC scores (P=0.055).

Nicotine-Induced Effects on Nicotinic Acetylcholine Receptors (nAChRs), Ca2+ and Brain-Derived Neurotrophic Factor (BDNF) in STC-1 Cells.

In addition to the T2R bitter taste receptors, neuronal nicotinic acetylcholine receptors (nAChRs) have recently been shown to be involved in the bitter taste transduction of nicotine, acetylcholine and ethanol. However, at present it is not clear if nAChRs are expressed in enteroendocrine cells other than beta cells of the pancreas and enterochromaffin cells, and if they play a role in the synthesis and release of neurohumoral peptides. Accordingly, we investigated the expression and functional role of nAChRs in enteroendocrine STC-1 cells. Our studies using RT-PCR, qRT-PCR, immunohistochemical and Western blotting techniques demonstrate that STC-1 cells express several α and ß nAChR subunits. Exposing STC-1 cells to nicotine acutely (24h) or chronically (4 days) induced a differential increase in the expression of nAChR subunit mRNA and protein in a dose- and time-dependent fashion. Mecamylamine, a non-selective antagonist of nAChRs, inhibited the nicotine-induced increase in mRNA expression of nAChRs. Exposing STC-1 cells to nicotine increased intracellular Ca2+ in a dose-dependent manner that was inhibited in the presence of mecamylamine or dihydro-ß-erythroidine, a α4ß2 nAChR antagonist. Brain-derived neurotrophic factor (BDNF) mRNA and protein were detected in STC-1 cells using RT-PCR, specific BDNF antibody, and enzyme-linked immunosorbent assay. Acute nicotine exposure (30 min) decreased the cellular content of BDNF in STC-1 cells. The nicotine-induced decrease in BDNF was inhibited in the presence of mecamylamine. We also detected α3 and ß4 mRNA in intestinal mucosal cells and α3 protein expression in intestinal enteroendocrine cells. We conclude that STC-1 cells and intestinal enteroendocrine cells express nAChRs. In STC-1 cells nAChR expression is modulated by exposure to nicotine in a dose- and time-dependent manner. Nicotine interacts with nAChRs and inhibits BDNF expression in STC-1 cells.

Hypercontractility of intestinal longitudinal smooth muscle induced by cytokines is mediated by the nuclear factor-κB/AMP-activated kinase/myosin light chain kinase pathway.

Recent studies have identified AMP-activated kinase (AMPK) as a target of Ca(2+)/calmodulin-dependent kinase kinase (CaMKKß) and a negative regulator of myosin light-chain (MLC) kinase (MLCK). The present study examined whether a change in expression or activity of AMPK is responsible for hypercontractility of intestinal longitudinal muscle during inflammation or in response to proinflammatory cytokines. In mouse colonic longitudinal muscle cells, acetylcholine (ACh) stimulated AMPK and MLCK phosphorylation and activity and induced MLC20 phosphorylation and muscle contraction. Blockade of CaMKKß with STO609 (7-oxo-7H-benzimidazo[2,1-a]benz[de]isoquinoline-3-carboxylic acid acetate) inhibited AMPK and MLCK phosphorylation and augmented MLCK activity, MLC20 phosphorylation, and smooth muscle cell contraction. In muscle cells isolated from the colon of TNBS (2,4,6-trinitrobenzenesulfonic acid)-treated mice or from strips treated with interleukin-1ß or tumor necrosis factor-α, nuclear factor κB was activated as indicated by an increase in p65 phosphorylation and IκBα degradation, and AMPK was phosphorylated at a cAMP-dependent protein kinase (PKA)-specific site (Ser(485)) that is distinct from the stimulatory CaMKKß site (Thr(172)), resulting in attenuation of ACh-stimulated AMPK activity and augmentation of MLCK activity and muscle cell contraction. Inhibition of nuclear factor-κB activity with MG-132 (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal Z-LLL-CHO) or PKA activity with myristoylated PKA inhibitor 14-22 amide blocked phosphorylation of AMPK at Ser(485) and restored MLCK activity and muscle cell contraction to control levels. The results imply that PKA released from IκBα complex phosphorylated AMPK at a PKA-specific site and inhibited its activity, thereby relieving the inhibitory effect of AMPK on MLCK and increasing MLCK activity and muscle cell contraction. We conclude that hypercontractility of intestinal longitudinal muscle induced by inflammation or proinflammatory cytokines is mediated by nuclear factor κB/PKA-dependent inhibition of AMPK and activation of MLCK.

Changes in the expression of smooth muscle contractile proteins in TNBS- and DSS-induced colitis in mice.

Thin filament-associated proteins such as calponin, caldesmon, tropomyosin, and smoothelin are thought to regulate acto-myosin interaction and thus, muscle contraction. However, the effect of inflammation on the expression of thin filament-associated proteins is not known. The aim of the present study is to determine the changes in the expression of calponin, caldesmon, tropomyosin, and smoothelin in colonic smooth muscle from trinitrobenzene sulphonic acid (TNBS)- and dextran sodium sulphate (DSS)-induced colitis in mice. Expression of h-caldesmon, h2-calponin, α-tropomyosin, and smoothelin-A was measured by qRT-PCR and Western blot. Contraction in response to acetylcholine in dispersed muscle cells was measured by scanning micrometry. mRNA and protein expression of α-actin, h2-calponin, h-caldesmon, smoothelin, and α-tropomyosin in colonic muscle strips from mice with TNBS- or DSS-induced colitis was significantly increased compared to control animals. Contraction in response to acetylcholine was significantly decreased in muscle cells isolated from inflamed regions of TNBS- or DSS-treated mice compared to control mice. Our results show that increase in the expression of thin filament-associated contractile proteins, which inhibit acto-myosin interaction, could contribute to decrease in smooth muscle contraction in inflammation.