Delineating the Disease Boundaries: Homozygous CDC14A Variants Underlying Nonsyndromic Hearing Loss and Hearing Impairment Infertile Male Syndrome.

Background: Hereditary hearing loss is a genetically heterogeneous neurosensory disorder that affects many people. Deafness and infertility can coexist in some cases, creating the hearing impairment infertile male syndrome. There are several known molecular mechanisms that can cause deafness either on its own or in conjunction with infertility. Methods and Results: Here, we represent two consanguineous families (A, B), both families had clinical evidence of deafness, and family B also had infertility, so we referred to them as having nonsyndromic hearing loss (NSHL) and hearing impairment infertile male syndrome (HIIMS), respectively. These families' genetic makeup was examined using an Affymetrix GeneChip 250K Nsp array followed by Sanger sequencing. In family A, we identified a novel homozygous stop gain variant [NM_003672.4; c.1000C>T; p.(Gln334*)] and a homozygous missense variant [NM_003672.4; c.684C>A; p.(Asn228Lys)] in family B in CDC14A gene (MIM#603504). In animal models, the CDC14A gene causes both hearing loss and infertility; in addition, it also causes NSHL and HIIMS in humans. Conclusions: Our study on the CDC14A gene has identified two novel variants, crucial for delineating disease boundaries. Variants in exon 10 and upstream cause HIIMS, and those in exon 11 and downstream are linked exclusively to hearing impairment. This precision enhances diagnostics and offers potential for targeted interventions, marking a significant advancement in understanding the genetic basis of these conditions.

Novel pathogenic variants in HR underlie atrichia with papular lesions in a cohort of 10 families.

Atrichia with papular lesions (APL) is a hair abnormality characterized by loss of hair on the scalp and rest of the body. In a few cases, hair loss is accompanied by the appearance of keratotic papules on the body. It is inherited in an autosomal recessive manner. Sequence variants in the HR (hairless) gene are responsible for this hair abnormality. Here, we present nine consanguineous families and one nonconsanguineous family with clinical manifestations of APL. Whole exome followed by Sanger sequencing and/or direct Sanger sequencing was performed to identify pathogenic variants. The study revealed seven novel pathogenic variants c.794del;p.(Pro265Argfs*98), c.2921-2936del;p.(Tyr974Leufs*16), c.2889C>A;p.(Cys963*), c.2689C>T;p.(Gln897*), c.3186_3187dup;p.(Gln1063Profs*43), c.560dup;p.(Tyr188Ilefs*131), c.2203+5G>C, c.2776+5G>A, and the previously reported variant c.1837C>T;p.(Arg613*) in HR in these families. The study not only expands the mutational spectrum in the HR gene but also highlights the unusual phenotypic findings and will facilitate genetic counseling of families with members showing various types of hair loss disorders in the local population.

Ultra-mini Percutaneous Nephrolithotomy (UM-PCNL) with a Semi-rigid Ureteroscope in Preschool Children: An Innovative Experience in Southern Iran.

PURPOSE: Percutaneous nephrolithotomy (PCNL) has undergone extensive modification to reduce complications. One of the recent advances in minimally invasive procedures is the advent of ultra-mini PCNL (UM-PCNL), which provides miniaturized access to the kidney. However, the specific instruments applied in UM-PCNL may not be found in centers with limited resources. This study evaluated the safety, feasibility, results, and short-term complication rates of performing UM-PCNL using a semi-rigid ureteroscope in preschool children. MATERIALS AND METHODS: Between September 2013 and September 2021, a total of 68 patients, including 42 boys and 26 girls with a mean age of 3.2 ± 2.4 years, underwent UM-PCNL with a 4.5French tip ureteroscope instead of an ultra-mini nephroscope in children aged less than 7 years old. The procedure was done under general anesthesia in the prone position. The nephrostomy tract was dilated to 12F. Stones were fragmented using a pneumatic lithotripter. Irrigation was done with normal saline. RESULTS: The early stone-free rate (SFR) was 91%, and the short-term total SFR was 97%. No statistically significant difference was found in pre-operative and post-operative Hb, BUN, Cr, Na+, and K+. Fever (11 patients) and ileus (5 patients) constituted the majority of complications, and only one patient required a blood transfusion. None of the cases undergoing UM-PCNL with this method required a re-do PCNL. CONCLUSION: Our experience shows that with sufficient experience in handling semi-rigid ureteroscopes, urologists practicing in centers with limited resources could perform UM-PCNL with relatively favorable outcomes.

Synergistic Effect of Maternal Micronutrient Supplementation on ORFV DNA Vaccine Immune Response in a Pregnant Model.

Contagious ecthyma is a contagious zoonotic disease caused by the Orf virus that can infect farm animals and humans, but no vaccine is available for pregnant mothers. Excessive oxidative stress during pregnancy can suppress the vaccine immune response in pregnant mothers; hence, maternal micronutrient supplementation could effectively improve the immune response, health, and oxidative status during pregnancy. In this study, we employed an 8-week-old pregnant rat model to receive a single intramuscular dose of 200 µg of ORF DNA vaccine with or without vitamin E and selenium supplementation to evaluate their effect on immune responses (specific IgG and IgG isotypes), oxidative stress, liver enzymes, and blood glucose levels in maternal-neonatal serum and milk secretions. Additionally, antioxidant-related gene expressions were analyzed in the maternal placenta and pups' liver. The results showed that supplementation of vitamin E and selenium with ORF DNA vaccination increased the production of specific antibody and IgG isotypes (IgG1 and IgG2a) and reduced the oxidative stress in neonatal-maternal serum and milk compared to both the control group and those vaccinated without supplementation (p < 0.05). Notably, the ORF DNA vaccine did not cause oxidative stress and hepatic damage. However, combined supplementation of vitamin E and selenium with DNA vaccination significantly decreased serum malondialdehyde (MDA) levels and improved the antioxidant-related enzyme activities of glutathione peroxidase (GPX), superoxide dismutase 1 (SOD1), and selenoprotein P (SELP) in the maternal placenta and liver of pups (p < 0.05). In conclusion, maternal supplementation of vitamin E and selenium enhanced the immune responses of the ORF DNA vaccine by mitigating oxidative stress in pregnant rats and could thus be a promising strategy for better health outcomes for both mothers and neonates.

Prevalence of Obesity and its Effects in Patients With COVID-19: A Systematic Review and Meta-analysis.

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease worldwide. Obesity has been proven to increase the susceptibility of an individual to infections, but the relationship between obesity and COVID-19 is still unclear. This study aimed to conduct a systematic review and meta-analysis of the prevalence of obesity and its effects in patients with COVID-19. Methods: Web of Science, PubMed and Embase were searched for English language studies up to May 22, 2020. We used a random or fixed-effects model to calculate pooled prevalence rates and odds ratio (OR) with 95% confidence intervals (CI). Results: Twelve studies with a total of 14 364 patients met the inclusion criteria. The pooled prevalence of obesity in patients with COVID-19 was 32.0% (95% CI, 26%-38%, P < .001). The prevalence of obesity in ICU COVID-19 patients were 37.0% (95% CI, 29%-46%, P < .001). Comparing between obese and non-obese patients, the meta-analysis showed that obesity was an important risk factor associated with COVID-19 patients needed for ICU care (OR: 1.36, 95% CI 1.22-1.52, P < .001). Conclusion: Obesity was highly prevalent (32.0%) in patients with COVID-19, especially in ICU patients (37.0%), and was an important risk factor for COVID-19 patients needed for ICU care.

Clinical and genetic investigation of 14 families with various forms of short stature syndromes.

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.

Effects of yeast culture on in vitro ruminal fermentation and microbial community of high concentrate diet in sheep.

This research aimed to investigate effects of different yeast culture (YC) levels on in vitro fermentation characteristics and bacterial and fungal community under high concentrate diet. A total of 5 groups were included in the experiment: control group without YC (CON), YC1 (0.5% YC proportion of substrate dry matter), YC2 (1%), YC3 (1.5%) and YC4 (2%). After 48 h of fermentation, the incubation fluids and residues were collected to analyze the ruminal fermentation parameters and bacterial and fungal community. Results showed that the ruminal fluid pH of YC2 and YC4 groups was higher (P < 0.05) than that of CON group. Compared with CON group, the microbial protein, propionate and butyrate concentrations and cumulative gas production at 48 h of YC2 group were significantly increased (P < 0.05), whereas an opposite trend of ammonia nitrogen and lactate was observed between two groups. Microbial analysis showed that the Chao1 and Shannon indexes of YC2 group were higher (P < 0.05) than those of CON group. Additionally, YC supplementation significantly decreased (P < 0.05) Succinivibrionaceae_UCG-001, Streptococcus bovis and Neosetophoma relative abundances. An opposite tendency of Aspergillus abundance was found between CON and YC treatments. Compared with CON group, the relative abundances of Prevotella, Succiniclasticum, Butyrivibrio and Megasphaera elsdenii were significantly increased (P < 0.05) in YC2 group, while Apiotrichum and unclassified Clostridiales relative abundances were decreased (P < 0.05). In conclusion, high concentrate substrate supplemented with appropriate YC (1%) can improve ruminal fermentation and regulate bacterial and fungal composition.

A Clinical Study of Intraoperative Perfusion Chemotherapy in Gastric Cancer: A Prospective Cohort Study.

INTRODUCTION: Gastric cancer (GC) is the third largest cause of cancer-related death worldwide, with major geographic disparities in incidence and outcomes. Sociodemographic indicators, food habits, and genetic predispositions all add to the load. Despite advances in systemic treatments, peritoneal metastasis remains a concern, with intraperitoneal chemotherapy (IPC) emerging as a promising treatment option. METHODS: A prospective cohort research was done, with 30 GC patients receiving cytoreductive surgery (CRS) followed by lobaplatin-based intraoperative chemotherapy. The study evaluated postoperative complications, survival rates, and disease recurrence using Statistical Package for the Social Sciences (SPSS) version 25.0 (IBM SPSS Statistics, Armonk, NY) for data analysis. The purpose of this study is to assess the effectiveness, safety, and dependability of lobaplatin as an intraoperative chemotherapeutic agent in patients having gastric cancer surgery, with a particular emphasis on those patients who do not have distant metastases. RESULTS: The study population had a balanced gender distribution, with an average age of 44.83 years. Most patients had advanced-stage cancer (T3 and T4), and lobaplatin treatment resulted in a low frequency of serious postoperative sequelae. Preliminary studies suggest that lobaplatin is a safe and potentially effective IPC drug for GC, with few side effects and adequate survival rates. CONCLUSION: Lobaplatin shows promise as an intraoperative chemotherapeutic treatment for gastric cancer, necessitating more research in bigger, randomized controlled studies to determine its efficacy and safety profile. The study emphasizes the need for novel treatment strategies to enhance the prognosis of GC patients, particularly those with peritoneal involvement.

A Clinical Study of Intraoperative Perfusion Chemotherapy With Raltitrexed in Colon Cancer: A Prospective Cohort Study.

INTRODUCTION: Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality among women and the third leading cause of cancer-associated mortality among men. Treatment of colon cancer is very crucial for a patient's survival. In this study, we assessed the reliability, efficacy, and safety of raltitrexed in intraoperative intraperitoneal chemotherapy for colon cancer. METHODOLOGY: A total of 57 patients with clinical stages II and III of colon cancer were included in the study. R0 resection surgery + hyperthermic intraperitoneal chemotherapy (HIPEC) procedure was done with raltitrexed. It was given in a dose of 3 mg/m2 in a 0.9% NS injection in a volume of 500 milliliters. Postoperative complications were observed. RESULT: The most common postoperative complication was nausea/vomiting, which was seen in 21 out of 57 patients (37%). The second most common complication was fever (18/57). None of the patients died or developed renal toxicity, hepatic toxicity, and intestinal obstruction. CONCLUSION: Raltitrexed is a reliable, efficient, and safe drug and can be used in intraoperative intraperitoneal chemotherapy of colon cancer.

Evaluation of the District Health Information System in District Kotli, Azad Jammu and Kashmir: A Retrospective Analysis.

BACKGROUND: It is essential to implement a high-quality electronic database for keeping important information. The District Health Information System (DHIS) is an active data-keeping system in Pakistan. This study aimed to evaluate the patients' data from the DHIS dashboard for the District Headquarters Hospital, Kotli, Azad Jammu and Kashmir (AJK). METHODOLOGY: The data was requested from the hospital administration at District Headquarters Hospital, Kotli, AJK, and the data was analyzed after permission was granted. The data was given in two forms; one was a hard copy of the data for August and September and the other was a comma-separated values file for October and November, 2023. RESULTS: The highest frequency of patients was received in the department of emergency and trauma and the patient's median age was between 15 and 49 years. The second department was medicine with the >50 years of age. Common conditions that needed more attention were chronic obstructive pulmonary disease, acute respiratory infection, diarrhea, pneumonia, diabetes mellitus, hypertension, and ischemic heart disease. CONCLUSION: For nations with constrained healthcare systems and funds, primary health care (PHC) is the only viable approach for managing non-communicable diseases (NCDs). However, PHC systems intended for infectious diseases have not sufficiently adapted to the growing requirement of chronic care for NCD. Research using health information databases offers numerous benefits, such as the evaluation of large data sets and unexpected prevalence of disease in certain populations, such as a higher prevalence of disease in one gender or age group. Health information system-based data analysis or studies are less expensive and faster but lack scientific control over data collection.