A Novel ANO1 Gene Variant is Associated with Intestinal Dysmotility Syndrome Masquerading as Hirschsprung Disease: A Case Report.

Anoctamin 1 (ANO1)-related intestinal dysmotility syndrome (OMIM: 620045) is an extremely rare disorder with only 2 cases reported in the medical literature. We present the clinical scenario of a 2-month-old male infant that presented to our center with diarrhea, vomiting, and abdominal distension. Routine investigations did not yield a clear diagnosis. Whole-exome sequencing showed a novel homozygous nonsense ANO1 pathogenic variant (c.1273G>T) with a protein alternation of p.Glu425Ter that fits the patient's phenotype. Sanger sequencing revealed the same ANO1 variant in both parents in a heterozygous form confirming an autosomal recessive mode of inheritance. The patient experienced multiple bouts of diarrhea-related metabolic acidosis, dehydration, and severe electrolyte imbalances that required intensive care unit monitoring. The patient was managed conservatively and being followed regularly in an outpatient setting.

Correlation of PKM2 Expression With HER2/neu and Additional Breast Cancer Biomarkers and its Prognostic Significance.

BACKGROUND: Pyruvate kinase M2 (PKM2) has a central role in both tumor development and metastasis, and it has increasingly become a valuable subject for many cancer studies due to its important prognostic value in various tumor types. In this study, we aimed to elucidate the impact of PKM2 expression level on breast cancer prognosis and survival rates and its association with various clinicopathologic characteristics and tumor markers in breast cancer patients. MATERIALS AND METHODS: This retrospective study included sample tissues from patients with breast cancer who did not receive chemotherapy or radiotherapy before surgery. Expression levels of PKM2, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67 were analyzed using tissue microarray and immunohistochemistry. RESULTS: A total of 164 patients were included with an age range from 28 to 82 years. High PKM2 was observed in 48.8% of cases (80/164). A significant association was found between PKM2 expression and breast cancer molecular subtype and HER2 status ( P <0.001). In HER2-negative tumors, there was a significant association between PKM2 expression and tumor grade, TNM stage, pN stage, lymphovascular invasion, and estrogen receptor/progesterone receptor status. Survival analysis revealed that high PKM2 expression levels were associated with decreased overall survival rate in HER2-positive cases with high Ki-67 index. Moreover, in the HER2-positive group, low PKM2 expression level impacted the survival outcome of metastasis ( P =0.002). CONCLUSIONS: PKM2 is a valuable prognostic and a potential diagnostic and predictive marker in breast cancer. Moreover, the combination of PKM2 with Ki-67 provides excellent prognostic accuracy in HER2-positive tumors.

COVID-19-related conspiracy beliefs and their determinants among 18 to 45 years old: A cross-sectional study.

The existence of conspiracy beliefs has been previously linked to multiple individual traits and factors, such as anxiety, lack of information, education, and social factors. This study aims to explore the factors and variables influencing the individual's susceptibility to conspiratorial thinking, as well as the impact of COVID-19 conspiracy belief on the adoption of public health and social measures. This study explores the factors influencing the susceptibility to conspiratorial thinking and the impact of conspiracy theories on the adoption of public health and social measures. A sample of university students, fresh-graduates, and mid-career professionals between the age of 18 to 45 years old completed an online survey measuring COVID-19 conspiracy beliefs and stress levels. A total of 2417 completed a survey targeting COVID-19 conspiracy beliefs, perceived stress, and demographic information. The results show that COVID-19 conspiracy beliefs were related to education, unemployment, and COVID-19 level of exposure. Meanwhile, conspiracy beliefs had no relation to the individual's perceived self-reported stress. Higher conspiracy scores were related to lower adoption of preventive measures and increased hesitancy towards COVID-19 vaccination. Lack of knowledge and misinformation actions play a vital role in the generation of conspiracy theories surrounding the COVID-19 pandemic.

Prevalence estimates of drug addiction among high-school students and its association with violence, and school behaviors: A cross-sectional study from Jordan.

INTRODUCTION: This study aims to estimate the prevalence of drug addiction among high-school students and its association with violence and school behavior. The present study provides baseline data focusing specifically on the extent of drug addiction and violence. METHODS: A cross-sectional study design was used. The questionnaire covered students' demographic profiles, including age, gender, and academic branch, and statements related to violent behaviors and school-related factors. A urine sample was collected from each participant to test for drugs and was analyzed by Multi-Drug Rapid Test Cup. RESULTS: Out of 440 students, a total of 414 were included in this study. Positive drug use via urine sample was confirmed in 70 students (16.9%), with 80% being males. Violent behaviors were common, including used to write on the walls (118, 28.5%), had problems with teachers (107, 25.9%) or peers (267, 64.5%), or using abusive language with school staff (63, 15.2%). There were no significant associations between drug addiction and these violent behaviors (p > 0.05). Students who had no respect for the teachers were significantly more in the addicted group (31.4%) than the non-addicted group (14%) (p = 0.004). CONCLUSION: High school should be identified as a critical period at risk for drug use and violent actions. This study points to the importance of early detection of drug addiction among vulnerable young people, enabling the development of educational programs to prevent abuse and dependence on substances.

Vitamin C attenuates memory loss induced by post-traumatic stress like behavior in a rat model.

Oxidative stress is associated with neuronal damage in many brain regions including the hippocampus; an area in the brain responsible of memory processing. Oxidative stress is also linked with many psychiatric conditions including post-traumatic stress disorder (PTSD). PTSD is triggered by traumatic experience and many PTSD patients show signs of memory impairment. Vitamin C is a water-soluble vitamin with antioxidant properties. Herein, we hypothesized that memory impairment observed during PTSD could be a result of oxidative stress in hippocampal tissues and that prophylactic vitamin C administration may reduce oxidative stress in the hippocampus and prevent memory impairment. The above hypothesis was tested in a rat model where PTSD-like behavior was induced through single prolonged stress (SPS). Short and long-term memory was tested using a radial arm water maze (RAWM). We found that SPS induced a significant increase in the oxidized glutathione levels of the hippocampus. This reduction was accompanied with a significant decrease in glutathione peroxidase and catalase enzyme activity, and a significant increase in lipid peroxidation. Intriguingly, vitamin C administration successfully attenuated memory impairment and all of the changes observed in oxidative stress markers. Our findings demonstrate that vitamin C could prevent oxidative stress and memory impairment induced by SPS model of PTSD-like behavior in rat.

Edaravone prevents memory impairment in an animal model of post-traumatic distress.

Post-traumatic stress disorder (PTSD) is a mental health problem that develops in a proportion of individuals after experiencing a potential life-threatening traumatic stress event. Edaravone is a free radical scavenger, with a neuroprotective effect against cognitive impairment in several animal models. In the present study, the protective effect of edaravone on PTSD-induced memory impairment was investigated. Single prolonged stress was used as an animal model of PTSD, comprising 2 h of restrain, 20-min forced swimming, 15-min rest, and 1-2-min diethyl ether exposure. Concurrently, edaravone was given at a dose of 6 mg/kg/day, intraperitoneally, for 21 days. The radial arm water maze was used to assess learning and memory. Antioxidant biomarkers were measured in hippocampus tissues. Chronic administration of edaravone prevented impairment of short-term and long-term memory. Edaravone also prevented the stress-induced decrease in the ratio of reduced glutathione/oxidized glutathione and the activities of glutathione peroxidase and catalase enzymes in the hippocampus, as well as increases in the levels of oxidized glutathione and thiobarbituric acid reactive substances. In conclusion, edaravone ameliorated oxidative stress and cognitive impairment associated with a PTSD model, probably by supporting antioxidant mechanism in the hippocampus.

A high weekly dose of cholecalciferol and calcium supplement enhances weight loss and improves health biomarkers in obese women.

Obesity, a chronic condition associated with several life-threatening diseases, affects a significant proportion of the global population and has long been associated with vitamin D deficiency. The prevalence of both obesity and vitamin D deficiency has increased dramatically in Jordan in recent decades, especially among women. Few studies in Jordan and the surrounding area address this issue. In this study, we hypothesize that calcium and vitamin D have beneficial effects on weight reduction and metabolic profile in obese women. The objective of this study is to examine the effect of vitamin D3 and calcium supplementation on anthropometric measurements and some blood metabolites. Forty-five obese female subjects with vitamin D deficiency were recruited by a dietitian and randomly assigned to the same weight loss diet in addition to the following treatments (4 groups): control (CON), no prescribed supplements; vitamin D3 (Diet/D), given a high weekly dose of cholecalciferol (50 000 IU/subject/week); calcium (Diet/Ca), given 1200 mg/dL calcium/subject/day; vitamin D3 plus Ca (Diet/Ca/D), given cholecalciferol (50 000 IU/subject/week) and calcium (1200 mg/dL calcium/subject/day). Results revealed that after 3 months of supplementation, the Diet/Ca/D group subjects experienced a significant reduction (P ≤ .05) in weight (10.49 kg), BMI (4.61 ± 2 kg/m2), waist circumference (11.41 ± 8.9 cm), body fat percentage (2.43 ± 1.7%), FBG (25.81 ± 11.4 mg/dL), PTH (27.58 ± 8.9 pg/mL), cholesterol (0.56 ± 0.2 mmol/L), and triglycerides (0.53 ± 0.21 mmol/L) when compared to the Diet/Ca and the CON groups. Interestingly, however, the CON group showed a significant increase in serum PTH concentration (9.51 ± 3.8 pg/mL, P ≤ .05). Based on these results, a combined Ca and vitamin D3 supplement appears to enhance weight loss and improve some of the blood metabolic profiles in obese women subjected to a weight loss diet, thus supporting our study hypothesis.

Phenelzine reduces the oxidative damage induced by peroxynitrite in plasma lipids and proteins.

Peroxynitrite is a reactive nitrogen species produced in the intravascular compartment from superoxide anion and nitric oxide. Peroxynitrite destroys blood plasma proteins and membranes of red blood cells and of platelets. This explains why excessive production of peroxynitrite contributes to diseases and to ageing. Therapeutics that antagonize peroxynitrite may delay ageing and the progression of disease. We developed an in vitro assay that allows the investigation of the oxidative damage caused by peroxynitrite in the intravascular compartment. This assay correlates the damage with the rate of formation of protein carbonyl groups, 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances. Using this assay, we evaluated the ability of phenelzine, a scavenger of reactive aldehydes, to antagonize the effects of peroxynitrite. Herein, we showed that phenelzine significantly decreased the lipid peroxidative damage caused by peroxynitirite in blood plasma and platelets. Moreover, it inhibited carbonyl group and 3-NT formation in blood plasma and platelet proteins.

Mechanisms and regulation of neurotrophin synthesis and secretion.

Neurotrophins are secreted proteins that are synthesized as pre-pro-neurotrophins on the rough endoplasmic reticulum, which are subsequently processed and then secreted as mature proteins. During synthesis, neurotrophins are sorted in the trans-Golgi apparatus into 2 pathways of secretion; the constitutive and the regulated pathways. Neurotrophins in the constitutive pathway are secreted cautiously without any trigger, while in the regulated pathway of secretion an external stimulus elevates the calcium concentration intracellularly leading to neurotrophin release. The regulation of sorting and secretion of neurotrophins is critical for several processes in the body, such as synaptic plasticity, neurodegenerative disorders, demyelination disease, and inflammation. The purpose of this review is to summarize the current mechanisms of neurotrophin sorting and secretion.

Cavernous Hemangioma of the External Canal, Tympanic Membrane, and Middle Ear Cleft: A Case Report.

Cavernous hemangioma involving the external canal, tympanic membrane, and middle ear cavity is extremely rare. We present a case of a 45-year-old woman who had progressive right sided decreased hearing, pulsatile tinnitus, and aural fullness of 7 months duration. Microscopic examination, imaging studies, surgical treatment, and histological evaluation are reported. To the best of our knowledge, this is the first case of cavernous hemangioma with simultaneous involvement of the external ear, tympanic membrane, middle ear, and attic reported in English literature.