The morbid genome of ciliopathies: an update.

PURPOSE: Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly. METHODS: Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes. RESULTS: In this study, we describe 125 families with ciliopathies and show that deleterious variants in previously reported genes, including cryptic splicing variants, account for 87% of cases. Additionally, we further support a number of previously reported candidate genes (BBIP1, MAPKBP1, PDE6D, and WDPCP), and propose nine novel candidate genes (CCDC67, CCDC96, CCDC172, CEP295, FAM166B, LRRC34, TMEM17, TTC6, and TTC23), three of which (LRRC34, TTC6, and TTC23) are supported by functional assays that we performed on available patient-derived fibroblasts. From a phenotypic perspective, we expand the phenomenon of allelism that characterizes ciliopathies by describing novel associations including WDR19-related Stargardt disease and SCLT1- and CEP164-related Bardet-Biedl syndrome. CONCLUSION: In this cohort of phenotypically and molecularly characterized ciliopathies, we draw important lessons that inform the clinical management and the diagnostics of this class of disorders as well as their basic biology.

Antibiotic Resistance & Extended-Spectrum ß-Lactamase Production in Clinical and Non-Clinical Isolates in Tabuk.

The increasing prevalence of antibiotic resistance, driven by the production of extended-spectrum beta-lactamases (ESBLs), presents a critical challenge to current medical treatments, particularly in clinical settings. Understanding the distribution and frequency of ESBL-producing bacteria is essential for developing effective control strategies. This study investigated the antibiotic resistance and extended-spectrum beta-lactamase (ESBL) production in bacterial isolates in clinical and non-clinical (food) specimens in Tabuk, KSA. A total of 57 bacterial isolates were analysed, with E. coli and Pseudomonas sp. being the most prevalent. High resistance rates were observed, particularly against third-generation cephalosporins in clinical isolates. ESBL screening revealed a significant prevalence in clinical samples (58.3%), with E. coli showing the highest positivity. Conversely, only a low percentage of food isolates were ESBL positive. Molecular analysis confirmed the presence of various ESBL genes, with blaCTX-M being the most frequent, predominantly found in clinical isolates. This study highlights the concerning levels of antibiotic resistance and ESBL production in the region, emphasising the need for effective infection control measures and prudent antibiotic use.

Awareness of Carpal Tunnel Syndrome Among the Adult Population in Northern Saudi Arabia.

Background Carpal tunnel syndrome (CTS) is the most prevalent entrapment neuropathy affecting the upper limb. It is recognized as a complex condition that is attributed to both non-medical and medical risk factors. Lack of awareness leads to delays in seeking advice, diagnosis, and treatment.  Objective To determine the awareness of CTS, its associated symptoms, signs, and risk factors among the adult population. Subjects and methods A cross-sectional study design was carried out among the adult population in Arar city, Northern Saudi Arabia.  Results In total, 338 respondents participated in this study. More than one-third (40.8%) mentioned that median nerve entrapment is a cause of CTS. The most commonly cited risk factor by the respondents was engaging in physical tasks such as using a computer (53%). Additionally, 60% of participants agreed that symptoms of CTS include tingling and numbness in the thumb, index, and middle fingers. Conclusion The findings of the study indicated a lack of adequate community awareness about CTS among the studied population.

Analysis of antibiotic regimens and outcomes in spinal brucellosis: insights from a retrospective cohort study in Makkah, Saudi Arabia.

Background: Brucellosis is a zoonotic disease that is widely spread across the globe, with the number of cases increasing annually. Spinal brucellosis is known to affect about half of patients with brucellosis. Nevertheless, data on the optimal antibiotic regimens for spinal brucellosis are limited. Therefore, this study aims to compare antibiotic treatment regimens for spinal brucellosis at our center in Makkah, Saudi Arabia. Methods: This is a retrospective cohort study of an 11-year period from 2010 to 2021 conducted at a single center in Makkah, Saudi Arabia. All patients with spinal brucellosis were included. Patients were excluded if the duration of the received antibiotic regimen or follow-up was poorly documented. Data analysis was conducted using RStudio (R version 4.1.1). Categorical variables of each regimen used by the patients were presented as frequencies and percentages, while numerical variables were summarized using the median and interquartile range (IQR). Results: A total of 35 patients were included; the median (IQR) age of the patients was 58.0 (48.0 to 63.0) years. The most frequently reported symptoms upon admission included low back pain (83.3%). The most frequently administered regimen was the combination of streptomycin + doxycycline + rifampicin (SDR) (20 patients, 55.6%), followed by the combination of streptomycin + rifampicin + trimethoprim/sulfamethoxazole (SRT) (eight patients, 22.2%). Overall, out of the total 35 patients who received first-line treatment, only six patients experienced therapy failure. Out of the total six patients who experienced first-line treatment failure with SDR (five patients, 83%) and SDT (one patient, 17%), surgery was indicated for three patients. Surgical intervention was deemed necessary in 12 patients (34%). Three patients chose not to undergo surgical intervention but still showed complete improvement upon completing the treatment duration. One patient experienced a postoperative complication, resulting in paraplegia. Conclusions: In this study, we found that among 35 patients, treatment failure was observed only in six patients who received triple therapy. In addition, surgical intervention was indicated in 12 patients; however, three patients refused surgery and improved ultimately after changing or extending the duration of the antibiotic regimen.

CBCT Evaluation of Root Canal Morphology of Maxillary First Premolar in Saudi Subpopulation.

Background and Objective: Clinicians must possess a comprehensive understanding of variations in canal morphology and configuration during endodontic procedures to enhance treatment success. This study aims to assess and analyze the canal configurations of maxillary first premolars using Cone-Beam Computed Tomography within the sub-population of Western Saudi Arabia. Materials and Methods: In this cross-sectional study, following the acquisition of ethical clearance from Batterjee Medical College in Jeddah, Saudi Arabia, a retrospective examination of Cone-Beam Computed Tomography (CBCT) scans of maxillary first premolars in adult patients was conducted. The study focused on quantifying the number of canals and characterizing their configurations, with classification based on Vertucci's categorization. Results: The study examined 399 CBCT images of maxillary first premolars, revealing that type IV canal configurations were the predominant morphology (56.9%), followed by type V (24.6%). Significant gender-related disparities were observed, with females displaying a higher incidence of types I and V canals. At the same time, males exhibited a greater prevalence of types IV and VI canals. Notably, no substantial associations were discerned between canal types and age groups. Conclusion: Within the context of maxillary first premolars, type IV canal configuration emerged as the most prevalent. Gender-based distinctions were evident, with females predominantly presenting types I and V canal configurations, whereas males displayed a higher occurrence of types IV and VI canal configurations.

Pseudoaneurysm and Renal Artery Stenosis Post-renal Transplant: A Rare Presentation.

We report the case of a 51-year-old gentleman who underwent living renal transplantation in Pakistan for end-stage renal disease one and a half years ago. He presented to our hospital with renal artery stenosis and an extra-renal pseudoaneurysm at the anastomotic site of the transplanted kidney. This can cause graft dysfunction and hypertension due to impairment of arterial perfusion in the transplanted kidney. Treatment with percutaneous transluminal angioplasty and covered stenting of the pseudoaneurysm and stenosis improved kidney function and hypertension.

Unraveling the Complex Relationship Between Gastroesophageal Reflux Disease, Lifestyle Factors, and Interstitial Lung Disease: Insights From Two-Sample Mendelian Randomization Analyses.

Background Although the cause of interstitial lung disease (ILD) remains uncertain, it is believed to be a combination of genetic and non-inherited factors, such as smoking and diet. This research aims to evaluate the impact of gastroesophageal reflux disease (GERD) and other modifiable risk factors on the likelihood of developing ILD by utilizing two-sample Mendelian randomization. Methodology The research utilized publicly accessible single-nucleotide polymorphisms (SNPs) that were deemed significant on a genome-wide scale. These SNPs were chosen from prior studies conducted by various consortia. The study examined GERD and a wide range of smoking habits, including the age at which individuals started smoking, the intensity of their smoking, and whether their mothers smoked. Additionally, the study considered other relevant risk factors such as key dietary factors, coffee consumption, body mass index (BMI), and physical activity. The study focused on self-reported ILD as its outcome measure. The genetic information for ILD was sourced from the FinnGen and UK Biobank (UKB) cohorts. Results The study encompassed a wide range of sample sizes, varying from 64,949 to 632,802, for each risk factor collected from multiple consortia. In total, 593 SNPs were included for all risk factors. The findings revealed significant associations between genetically estimated GERD, dietary factors, BMI, and the risk of ILD within the FinnGen consortium. The odds ratios (ORs) indicated an increase in the risk of ILD per unit of GERD (OR = 1.17, p = 0.001), smoking initiation (OR = 1.10, p < 0.05), BMI (OR = 1.15, p = 0.006), and low-density lipoprotein (LDL) (OR = 1.10, p = 0.02). On the other hand, there was a decrease in the risk of ILD per unit increase in coffee intake (OR = 0.64, p = 0.01) and physical activity (OR = 0.79, p=0.03). Additionally, the results demonstrated a significant association between genetically estimated GERD (OR = 1.01, p < 0.05), coffee intake (OR = 1.14, p=0.03), and high-density lipoproteins (HDL) (OR = 1.01, p=0.04) and increased risk of ILD specifically within the UKB. Conclusions This research indicates that the development of ILDs may be causally associated with GERD and various factors such as coffee intake, smoking, BMI, physical activity, LDL, and HDL These results hold great importance in terms of devising effective strategies for the treatment and prevention of ILDs.

Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy effects on obesity comorbidities: A systematic review and meta-analysis.

Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are the most commonly used bariatric procedures. There is an increasing awareness about a comorbidity-based indication for bariatric surgery regardless of weight (metabolic surgery). The best operation to mitigate obesity-associated comorbidities is a matter of controversy. This review is aimed at comparing LRYGB and LSG for the treatment of diabetes, hypertension, dyslipidemias, obstructive sleep apnea (OSA), and gastroesophageal reflux (GERD). We searched PubMed, MEDLINE, SCOPUS, Web of Science, and Cochrane library for articles comparing these two commonly used bariatric approaches. We identified 2,457 studies, 1,468 of which stood after the removal of duplications; from them, 81 full texts were screened and only 16 studies were included in the final meta-analysis. LRYGB was equal weight to LSG for diabetes (P-value = 0.10, odd ratio, 1.24, 95% CI, 0.96-1.61, I 2 for heterogeneity = 30%, P-value for heterogeneity, 0.14), and OSA (P-value = 0.38, odd ratio, 0.79, 95% CI, 0.47-1.33, I 2 for heterogeneity = 0.0%, P-value for heterogeneity, 0.98). However, LRYGB was superior to LSG regarding hypertension (P-value = 0.009, odd ratio, 1.55, 95% CI, 1.20-2.0, I 2 for heterogeneity = 0.0%, P-value for heterogeneity, 0.59), dyslipidemia (odd ratio, 2.18, 95% CI, 1.15-4.16, P-value for overall effect, 0.02), and GERD (P-value = 0.003, odd ratio, 3.16, 95% CI, 1.48-6.76). LRYGB was superior to LSG for gastroesophageal reflux, hypertension, and dyslipidemia remission. While the two procedures were equal regarding diabetes and obstructive sleep, further reviews comparing LSG, and one anastomosis gastric bypass are recommended.

Knowledge and Practice of and Attitude Toward Epidural Analgesia Among Pregnant Women in Jazan Region of Saudi Arabia.

The aim of this study was to assess the knowledge, sources of knowledge, attitudes (fears and misconceptions) toward epidural analgesia (EA), and practices of parturient delivery in the Jazan region of Saudi Arabia. A cross-sectional study was conducted using a self-administered survey questionnaire distributed in the antenatal care clinics of the obstetric departments of major hospitals. A total of 454 women participated in this study. Of the participants, 219 (48%) belonged to the 31 to 40-year age group and 134 (30%) to the 21 to 30-year age group. Most participants (344, 76%) had a bachelor's degree. The prevalence of epidural catheter use was 23.6% among pregnant women. Statistically significant differences in educational level and residence were found between the women (p < 0.001). The two most common sources of information cited by the pregnant women were healthcare staff and family and friends. The most common motive reported by women was to relieve labor pain effectively, and the most frequently cited barriers preventing women from receiving EA were the possibility of injury to important organs and the inability to walk after EA. The present study demonstrates a low level of knowledge about EA among pregnant women in the region. More awareness and guidance about EA are warranted.

The Cross-Talk Between Atopic Dermatitis and Diabetes Mellitus: A Meta-Analysis.

INTRODUCTION: Atopic dermatitis (AD) is associated with various systemic diseases. However, its association with diabetes mellitus (DM) was discussed controversially. Few researchers reviewed the association of these two common morbid disorders. This meta-analysis aimed to assess the relationship between AD and DM. METHODS: We systematically searched PubMed including Epub and ahead of print (198 articles identified) and Cochrane (13 articles) databases. The searching engine was set to include case-control, prospective and retrospective cohorts, and cross-sectional studies from the first published up to February 12, 2021. Two hundred and eleven were identified, eighteen full texts were screened; of them, six were included in the final meta-analysis. The keywords used were AD, diabetes mellitus, type 1 diabetes, and type 2 diabetes. A datasheet was used to record the author's name, year of publication, country and type of the studies, number of events, and total number in the two arms (patients and controls). RESULTS: Out of the 211 references identified, six studies were pooled to test the association between diabetes mellitus and AD. The studies showed that AD is lower among patients with DM, odds ratio, 0.69, 95% CI, and 0.67-0.72. No heterogeneity was observed (Chi-Square, 4.12, degree of freedom (df.)= 5, and I2 = 0%, P-value), 0.53 and P-value for overall effect, <0.001. The included studies were published in Europe (five) and Canada (one study) and included 162,882 patients and 12,164 events, four of the studied articles were case-control studies, one retrospective, and one cross-sectional. CONCLUSION: AD was lower among patients with DM compared to their counterparts without the disease. Further studies focusing on the genetic and environmental factors linking AD and diabetes are needed.

Epidemiological and Clinical Characteristics of Deceased COVID-19 Patients.

OBJECTIVE: Fatalities due to coronavirus disease 2019 (COVID-19) continue to increase, and information on the epidemiological and clinical characteristics of deceased patients who were hospitalized with COVID-19 is limited in the Arab region. The current study aimed to address this gap. METHODS: Three hundred and four Saudi patients in Jazan Region, Saudi Arabia, who died after being hospitalized with COVID-19 between July 1, 2020, and December 31, 2020, were analyzed in this retrospective cohort study. RESULTS: A greater proportion of male patients (59%), compared to female patients (41%), died due to COVID-19. Just over half (55%) of the deaths due to COVID-19 affected patients aged ≥65 years. More than two-thirds of the deceased COVID-19 patients had diabetes (70%) and hypertension (69%); other comorbidities were obesity (30%), heart disease (30%), and chronic kidney disease (14%). Dyspnea (91%), cough (80%), and fever (70%) were the most frequently reported clinical symptoms. Eighty-five per cent of COVID-19 deaths occurred in patients admitted to the intensive care unit (ICU), and 90% of the patients required mechanical ventilation. Typically, lymphopenia, and neutrophilia were observed on admission and 24 hours prior to death. Creatinine and serum ferritin levels and erythrocyte sedimentation rate and D-dimer plasma levels increased significantly following infection with COVID-19. Lung infiltrates and pulmonary opacity (83%) were the most common findings on chest X-ray. Respiratory failure (70%) and acute respiratory distress syndrome (52%) were the leading complications to death. Logistic and Cox regression revealed that a higher age, smoking, high creatinine and aspartate transaminase levels, and respiratory failure were significantly associated with the risk of mortality during the early stay in hospitals. CONCLUSION: The proportion of comorbidities was high in deceased patients who were hospitalized with COVID-19 in Jazan region, Saudi Arabia. A higher age, smoking, and respiratory failure were significant predictors of mortality during the early stay in hospitals.

ERCC1, XRCC1 and GSTP1 Single Nucleotide Polymorphisms and Survival of Patients with Colon Cancer Receiving Oxaliplatin-Based Adjuvant Chemotherapy.

BACKGROUND: While single nucleotide polymorphisms (SNP) in genes involved in DNA repair or drug metabolism have been shown to influence survival of metastatic colon cancer patients treated with FOLFOX, data on adjuvant setting are scarce. METHODS: This study evaluated the correlation between disease-free survival (DFS) of 210 unselected stage III colon cancer patients receiving FOLFOX chemotherapy, and ERCC1-118 (rs11615, c.354T>C), XRCC1-399 (rs25487, c.1196G>A) and GSTP1-105 (rs1695, c.313A>G) polymorphisms. SNP were determined on tumor DNA using a PCR-based RFLP technique. RESULTS: In univariate analysis, a trend towards longer DFS was observed for ERCC1 (C/T + T/T) versus (C/C) (HR=2.29; p=0.06), and XRCC1 (A/A) versus (G/G + G/A) (HR=1.61; p=0.16), but not for GSTP1 genotypes; a statistically significant p value was obtained when combining ERCC1 and XRCC1 favorable genotypes (0 versus ≥ 1 favorable genotypes, HR=2.42; p=0.02). After adjustment on tumor stage, lymph node ratio and differentiation grade, multivariate analysis showed that combining ERCC1 and XRCC1 genotypes gave a p value slightly above the threshold for statistical significance (HR=2.03; p=0.06), which was lower than for tumor stage, lymph node ratio or differentiation grade. CONCLUSION: The association of ERCC1 and XRCC1 polymorphisms may influence the prognosis of stage III colon cancer patients treated with FOLFOX adjuvant chemotherapy. Yet, these findings need to be confirmed in independent prospective studies.