Number of factors, including newly emerging infectious diseases and an increase in multi-drug resistant microbial pathogens with particular relevance for Gram-positive bacteria, make the treatment of ...infectious diseases in hospital-based healthcare a major challenge in the medical community. 4-Aminobenzoic acid (PABA), has demonstrated a variety of biological actions particularly, antimicrobial activity. In our study we coupled this vitamin-like molecule with different isatin derivatives. We investigated the antibacterial activity of the synthesized Schiff's bases. The compounds showed high selective activity against Gram-positive bacteria and showed weak or no activity against both Gram-negative bacteria and fungi. Compound 2a showed highest activity against S. aureus and B. subtilis (MIC 0.09 mmol/L). Additionally, these substances exhibit strong anti-B. Subtilis biofilm formation. We were able to shed insight on the binding mode of these new inhibitors using in silico docking of the compounds in the binding sites of a 3D structure of B. subtilis histidine kinase/Walk. The binding free energy of the compound 2a to the catalytic domain walk, of histidine kinase enzyme of B. subtilis bacteria, was calculated using molecular mechanics/generalized born surface area scoring. The key residues for macromolecule–ligand binding were postulated. The optimized 3D protein–ligand binding modes shed light on the B. subtilis HK/Walk–ligand interactions that afford a means to assess binding affinity to design new HK/Walk inhibitor as antibacterial agents.
Obesity is common among chronic obstructive pulmonary disease (COPD) patients and is associated with an increase in acute exacerbation episodes. However, data on obesity's impact on and association ...with clinical outcomes among patients with COPD are limited. This study aimed to determine overweight and obesity prevalence and associations with spirometry profiles, intensive care unit (ICU) admission, and comorbidities in patients with COPD.
In this retrospective cohort study, we reviewed the electronic health records of adult individuals diagnosed with COPD who visited the studied pulmonary clinics between 1 January 2018 and 31 December 2022 and then collected key demographic variables and relevant clinical outcomes and comorbidities.
A total of 474 patients with COPD were included in the final analysis, of whom 60% were male. The occurrences of overweight and obesity were 32.7% and 38.2%, respectively. The presence of comorbidities was high in obese patients (78.4%), followed by overweight patients (63.8%) with COPD. Obese and overweight patients had the highest ward admission rates (38.3% and 34.2%, respectively). ICU admissions were higher in obese and overweight patients (16% and 12%, respectively) compared with normal-weight patients (9%). Although no significant correlation was found between body mass index and spirometry parameters, comorbidities and ICU admission were linked to overweight and obesity in COPD patients (AOR: 1.82 95% CI: 1.15 to 2.86 and AOR: 3.34 95% CI 1.35 to 8.22, respectively).
Our findings imply that obesity in COPD is prevalent and is associated with adverse clinical outcomes including a greater number of comorbidities and higher rates of hospitalization and admission to ICUs although no associations were found between body weight and spirometry parameters. Further studies are needed to assess whether implementing and optimising obesity screening and management at an early stage in COPD can prevent further deterioration.
Background Vaccine hesitancy is a growing concern worldwide, particularly during the COVID-19 pandemic. The aim was to investigate vaccine hesitancy and its determinants among parents in Taif, Saudi ...Arabia. Methods A cross-sectional study was conducted among parents using a validated and reliable questionnaire, the parent attitudes about childhood vaccines (PACV). Parents of children aged (two months to seven years) attending primary health care centers (PHCC) outpatient clinics were selected using a stratified sampling technique and interviewed to fill out the pre-structured questionnaire. Result The study included 301 parents, with 41.2% between the ages of 30-39 years and 25.2%% between 40-49 years. Mothers constituted 69.1% of the respondents. The most common sources of information regarding vaccinations were the doctor (34.9%), the internet (27.9%), and social media (16.6%). COVID-19 influenced the beliefs of more than half (52.5%) of parents regarding the importance of vaccinations. The median PACV score for vaccination hesitancy was 23.3/100, interquartile range (IQR) (13.3-33.3). The highest hesitation was among the age group of 30-39 years old (21.6%) and those whose beliefs were not influenced by the COVID-19 pandemic (16.1% vs. 5.7%) (p-value=0.003). The study found a significant difference in vaccine hesitancy rates between the different sources of information (p-value <0.001); parents who got their information about vaccinations from social media were more likely to be hesitant about vaccinations (40%). Concerns about side effects (93.8%), thinking that vaccines are not safe (84.4%), and thinking that fewer vaccines are needed (78.1%) were the top three factors influencing vaccine hesitancy. Conclusion This study urges promoting vaccine uptake through healthcare providers and combating vaccine misinformation on social media. Additionally, addressing safety concerns and misconceptions about vaccine necessity, and focusing on first-time parents, younger parents, and those with lower socioeconomic status are recommended strategies to improve vaccine uptake rates.
Pulmonary hypertension is a common and serious complication of chronic obstructive pulmonary disease (COPD). Studies suggest that cigarette smoke can initiate pulmonary vascular remodelling by ...stimulating cell proliferation; however, the underlying cause, particularly the role of vasoactive prostanoids, is unclear. We hypothesize that cigarette smoke extract (CSE) can induce imbalanced vasoactive prostanoid release by differentially modulating the expression of respective synthase genes in human pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs), thereby contributing to cell proliferation.
Aqueous CSE was prepared from 3R4F research-grade cigarettes. Human PASMCs and PAECs were treated with or without CSE. Quantitative real-time RT-PCR and Western blotting were used to analyse the mRNA and protein expression of vasoactive prostanoid syhthases. Prostanoid concentration in the medium was measured using ELISA kits. Cell proliferation was assessed using the cell proliferation reagent WST-1.
We demonstrated that CSE induced the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostanoid synthesis, in both cell types. In PASMCs, CSE reduced the downstream prostaglandin (PG) I synthase (PGIS) mRNA and protein expression and PGI
production, whereas in PAECs, CSE downregulated PGIS mRNA expression, but PGIS protein was undetectable and CSE had no effect on PGI
production. CSE increased thromboxane (TX) A synthase (TXAS) mRNA expression and TXA
production, despite undetectable TXAS protein in both cell types. CSE also reduced microsomal PGE synthase-1 (mPGES-1) protein expression and PGE
production in PASMCs, but increased PGE
production despite unchanged mPGES-1 protein expression in PAECs. Furthermore, CSE stimulated proliferation of both cell types, which was significantly inhibited by the selective COX-2 inhibitor celecoxib, the PGI
analogue beraprost and the TXA
receptor antagonist daltroban.
These findings provide the first evidence that cigarette smoke can induce imbalanced prostanoid mediator release characterized by the reduced PGI
/TXA
ratio and contribute to pulmonary vascular remodelling and suggest that TXA
may represent a novel therapeutic target for pulmonary hypertension in COPD.
Purpose: Many risk factors, such as the duration of surgery and higher ASA scores, are associated with longer hospitalization in patients undergoing orthopedic surgery. However, no studies have ...evaluated the relationship between the preoperative systemic immune-inflammation index (SII) and length of hospital stay in orthopedic surgical patients. Therefore, this study aimed to investigate whether the SII is associated with the length of hospital stay in orthopedic surgery in adults. Patients and Methods: This was a retrospective cohort study, and data were extracted from electronic health records. Patients were included if they were older than 18 years and had undergone orthopedic surgery between 2016-2021. The patients were divided into two groups according to the median duration of hospitalization and according to SII cut-off value (high-SII group: greater than or equal to799.86, low-SII group: <799.86). Univariate and multivariate linear regression analyses were used to identify the association between SII and length of hospitalization. Results: A total of 196 patients who underwent orthopedic surgery were included, and 62 were hospitalized for >21 days. There were significant differences in terms of ASA score (P = 0.041). Patients who required a longer hospitalization of >21 days had significantly lower hemoglobin level (P < 0.001), higher duration of surgery (P = 0.015), and increased requirement of ICU admission (P < 0.001). The optimal cut-off value for preoperative SII of 799.86 stratified the patients into high-SII and low-SII groups. Patients in high-SII group had higher median LOHS (22 days) compared to low-SII group (17 days; P = 0.006). In the multivariable linear regression analysis, the SII was significantly related to the length of hospital stay (beta = 0.246, 95% confidence interval CI 0.000-0.005, P = 0.031). Conclusion: A high-SII value is associated with an increased risk of longer hospitalization after orthopedic surgery. Keywords: systemic immune-inflammation index, neutrophils, platelets, lymphocytes, hospital stay, orthopedic surgery
Background: Immune checkpoint inhibitors (ICIs) offer a new treatment approach for cancer, with an improvement in patient survival. However, it remains unclear whether their use impacts the quality ...of life of treated patients. This study aims to compare the health-related quality of life (HRQoL) of patients treated with different anti-PD-1 and anti-PD-L1 drugs, including several single or combination therapies. Methods: This is a prospective observational study conducted with adult cancer patients who received at least one dose of anti-PD-1 or anti-PD-L1. The HRQoL of all adult patients was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 module (QLQ-C30), version 3, Arabic version. Results: A total of 199 patients were found to be eligible for this study. Of these, 93 patients (82 on a single medication and 11 on multiple ICIs) completed the questionnaire, with a response rate of 46.7%. The majority of patients were treated with pembrolizumab (39.8%), followed by a smaller number treated with nivolumab (35.5%). Most of the patients were diagnosed with solid and advanced malignancies—88.2% (p = 0.023) and 87.1% (p = 0.021), respectively—with a significant difference between treatment groups. The median functioning score was 84.7%, with no significant difference between treatment groups (p = 0.752). Fatigue and pain were noted in >50% of patients, influencing the overall cohort’s score related to these symptoms, with scores of 88.8% and 83.3%, respectively. Although a non-significant variation was found in the scores of all combined symptoms among all groups, ranging from 82.1% to 90.4% (p = 0.931), patients receiving anti-PD-1 + anti-PD-L1 tended to more frequently complain about fatigue, pain, dyspnea, and constipation and hence, exhibited the worst, yet non-significant, scores compared to those of the other groups, with p = 0.234, p = 0.79, p = 0.704, and p = 0.86, respectively. All combined groups scored 83.3% on the global health scale. Nevertheless, the nivolumab-treated patients scored 75%, which was the worst global health score compared with those of the other groups, but this score was not statistically significant (p = 0.809). Conclusions: Our findings revealed no significant difference in the impact of different ICIs on the HRQoL of cancer patients. However, a larger number of cases would be necessary to provide a robust analysis and to yield conclusive results.
Introduction Laryngopharyngeal reflux (LPR) is a condition characterized by the backflow of gastric contents rising through the esophagus, affecting the aerodigestive tract and leading to throat ...symptoms such as hoarseness, chronic cough, and throat clearing. LPR is recognized as a separate condition from gastroesophageal reflux disease, despite the fact that they both involve the backflow of the stomach contents as their primary pathology. Our study aimed to evaluate the prevalence of LPR within the population of Saudi Arabia. Methods A cross-sectional study was conducted using an electronic questionnaire from August to November 2023, involving participants from all five regions of Saudi Arabia. A total of 1140 participants completed the questionnaire, which included the Reflux Symptom Index (RSI) to assess the prevalence of LPR. Results LPR was found to be prevalent in 31.2% of the study population, with the most common associated demographics being female gender (p = 0.032) and adults aged 36-45 years (p = 0.006). However, no significant relationship was observed based on region of residence or other demographic factors such as education level or occupation. Conclusion LPR has a high prevalence in the population of Saudi Arabia. Therefore, further research and awareness about this condition are warranted to better understand its impact, improve diagnosis, and develop appropriate management strategies.
To identify the most important research topics to establish a national research agenda and protocol for prehospital research in Saudi Arabia (KSA).
A 3-round modified Delphi consensus methods were ...used to determine high-priority research topics. Round I included an open-ended question to list all high-priority research topics in a prehospital setting in Riyadh, KSA. Rounds II and III included ranking evaluation and consensus agreement. The included topics were listed based on the agreement of ≥70% of the experts participating in the study. The study was carried out between November 2021 and February 2022.
In total, 100 prehospital experts in KSA were invited to participate in all 3 rounds. Of these, 47 responded in round I, 34 in round II, and 39 in round III. In round I, participants submitted 278 research topics. After deduplication and sorting, 78 topics were assessed in the other 2 rounds.
In this modified Delphi study, an expert panel identified the top prehospital emergency medical services (EMS) care research priorities. The leading research priorities included clinical and operational ideas. The proposed 32 high-priority topics can be used to guide researchers, research networks, policymakers, and funding organizations involved in EMS.
Background End-of-life care is essential for individuals with advanced illness and their families, providing comfort, symptom control, and dignity in the final year of life. Additionally, physician ...competence requires the ability to communicate, make decisions, and create relationships in end-of-life care. This study assesses family physicians' knowledge and attitude regarding end-of-life care in Taif, Saudi Arabia. Methods This descriptive cross-sectional study conducted between October and November 2021 assessed the knowledge and attitudes of 163 family physicians in Taif City, Saudi Arabia, regarding end-of-life care. Using a convenient sampling technique, an adapted and validated questionnaire was administered electronically, collecting sociodemographic information and assessing participants' knowledge and attitudes. Data were analyzed using descriptive statistics in Statistical Product and Service Solutions (SPSS, version 28) (IBM SPSS Statistics for Windows, Armonk, NY). Results Findings included that 41.1% of residents believed the patient and family should be informed about diagnoses and prognoses in advanced diseases. At the same time, attitudes varied, with 45.4% agreeing that discussing such information could lead to patient depression and 42.9% believing it held no privilege for patients. Additionally, 57.7% recognized that grief reactions would occur, but patients would eventually adjust, and 44.8% agreed that discussing diagnoses would decrease patient anxiety. However, limited awareness of advance directives was evident, with 12.3% reporting being well aware and 45.4% having never heard of them. There was uncertainty and hesitancy regarding Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decisions, with 39.9% being well aware and 46% having heard of it without a strong understanding. Conclusion The findings revealed a mixed landscape, with physicians demonstrating awareness of the importance of transparent communication but needing more knowledge in areas such as advance directives and complex decision-making. The study highlighted the need for targeted education to address these gaps and promote a more informed and consistent approach to end-of-life care.
Myoclonus dystonia (MDS) is a dominantly inherited genetic disorder caused by loss-of-function mutations in the epsilon sarcoglycan gene (SGCE).
We here in report a twenty months old Saudi boy who ...presented to us with a concern that the child is unable to walk properly. On assessment, he was flexing his left arm and left leg that usually followed by a back-ward fall. Diagnosis of dystonia induced with initiation of movement was suggested that later on proven genetically to be pathogenic mutation of sarcoglycan gene. Carbamazepine therapy was initiated with dramatic response. Response was maintained at 4 years follow up.
Our patient and the other previously reported cases might highlight the response of SGCE mutations to carbamazepine therapy.
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