Identification of the interfacial regions in misfolded transthyretin oligomers.

Misfolding and aggregation of transthyretin (TTR) is associated with numerous ATTR amyloidosis. TTR aggregates extracted from ATTR patients consist of not only full-length TTR, but also N-terminally truncated TTR fragments that can be produced by proteolytic cleavage, suggesting the presence of multiple misfolding pathways. Here, we report mechanistic studies of an early stage of TTR aggregation to probe the oligomerization process for the full-length as well as N-terminally truncated TTR. Our kinetic analyses using size exclusion chromatography revealed that amyloidogenic monomers dissociated from wild-type (WT) as well as pathogenic variants (V30M and L55P) form misfolded dimers, which self-assemble into oligomers, precursors of fibril formation. Dimeric interfaces in the full-length misfolded oligomers were investigated by examining the effect of single-point mutations on the two ß-strands (F and H). The single-point mutations on the two ß-strands (E92P on strand F and T119W on strand H) inhibited the dimerization of misfolded monomers, while the TTR variants can still form native dimers through the same F and H strands. These results suggest that the two strands are involved in intermolecular associations for both native and misfolded dimers, but detailed intermolecular interactions are different in the two forms of dimers. In the presence of a proteolytic enzyme, TTR aggregation is greatly accelerated. The two mutations on the two ß-strands, however, inhibited TTR aggregation even in the presence of a proteolytic enzyme, trypsin. These results suggest that the two ß-strands (F and H) play a critical role in aggregation of the N-terminally truncated TTR as well.

The impact of middle meatal steroid-eluting implants on the postoperative outcomes of chronic rhinosinusitis: A systematic review and meta-analysis.

Endoscopic sinus surgery (ESS) has become an established surgical option in refractory chronic rhinosinusitis (CRS). The goal of this review is to assess the impact of steroid-eluting middle meatal implants after ESS. Cochrane Central Register of Controlled Trials (CENTRAL), SCOPUS, PUBMED, and GOOGLE SCHOLAR were searched from inception to November 2022. All randomised controlled trials (RCTs) involving adult patients receiving ESS for CRS utilising a steroid-eluting middle meatal implants were eligible. The primary outcome was adhesion or synechiae. The secondary outcomes were mucosal inflammation, polyp reformation, the need for oral steroids and additional surgery, postoperative bleeding, sinus pain and discomfort, postoperative sinus-related infection, and change in intraocular pressure. Fourteen full articles were examined out of 496 potential abstracts. Seven RCTs satisfied the criteria. At 30days, steroid-eluting implants reduced adhesion (OR: 0.28, 95% CI: 0.14 to 0.56; P<0.001), mucosal inflammation (MD: -13.09, 95% CI: -18.22 to -7.97; P<0.001), polyp reformation (OR: 0.31; 95% CI: 0.22 to 0.44; P<0.001), and requirement of additional oral steroid (OR: 0.44; 95% CI: 0.25 to 0.78; P=0.005) or surgery (OR: 0.25; 95% CI: 0.12 to 0.50; P<0.001). While their use for adhesion (OR: 0.24; 95% CI: 0.11 to 0.54; P<0.001) and polyp reformation (OR: 0.24; 95% CI: 0.12 to 0.51; P<0.001) were favourable, there was no difference in mucosal inflammation (MD: -5.68, 95% CI: -12.39 to 1.03; P=0.100) or the need for surgery (OR: 0.96; 95% CI: 0.07 to 12.37; P=0.980) when evaluated after 30days. Overall, the findings suggest that steroid-eluting middle meatal implants improve ESS outcomes by lowering rates of adhesion formation, postoperative medical and surgical interventions, recurrent polyposis, and inflammation, while having no significant negative impact in the immediate postoperative period. More research is needed into the long-term impacts.

Angiopoietin as a Novel Prognostic Marker in Kidney Disease.

INTRODUCTION: Renal injury is among the leading causes of morbidity and mortality; however, there are no reliable indicators for determining the likelihood of developing chronic kidney disease (CKD), CKD progression, or AKI events. Vascular growth factors called angiopoietins have a role in endothelial function, vascular remodeling, tissue stabilization, and inflammation and have been implicated as prognostic and predictive markers in AKI. METHODS: Although the exact mechanism of the relationship between kidney injury and angiopoietins is unknown, this review demonstrates that AKI patients have higher angiopoietin-2 levels and that higher angiopoietin-1 to angiopoietin-2 ratio may potentially be linked with a reduced risk of the CKD progression. RESULTS: This review therefore emphasizes the importance of angiopoietin-2 and proposes that it could be an important predictor of AKI in clinical settings. CONCLUSION: There is a need for further large-scale randomized clinical trials in order to have a better understanding of the significance of angiopoietin-2 and for the determination of its potential clinical implications.

Is there any robust evidence showing that SGLT2 inhibitor predisposes to cancer?

BACKGROUND: The exact pathophysiological mechanisms of SGLT-2 inhibitors in the development, progression or treatment of malignancies are not fully understood, but multiple hypotheses have been proposed. SGLT-2 inhibitors have potential anti-proliferative roles due to several underlying pathophysiological mechanisms, such as inhibition of ATP production, activation of AMPK signalling, induction of apoptosis and ferroptosis, inhibition of glutamate dehydrogenase activity and inhibition of DNA and RNA synthesis. However, heterogeneity among tumour cells and SGLT-2 inhibitor drugs limit the generalizability of pre-clinical studies. METHODS: This is a narrative review discussing the potential anti-cancer effects of SGLT-2 inhibitors, an oral glucose-lowering medication used in patients with type II diabetes mellitus. This review discusses underlying mechanisms, pre-clinical and clinical trial data, epidemiological data and future perspectives on the use of SGLT-2 inhibitors in cancer treatment. RESULTS: Type II diabetes is linked to various comorbidities and malignancies, but some glucose-slowering medications may have a preventive role in cancer. The use of SGLT-2 inhibitors was associated with bladder cancer based on mice studies. However, meta-analyses showed no significant increase in overall malignancy incidence of any specific type, except for empagliflozin and bladder cancer association. SGLT-2 inhibitors can potentially reduce the heart damage caused by doxorubicin and sunitinib, while enhancing the anti-cancer effects of doxorubicin. Combining SGLT-2 inhibitors with doxorubicin may allow higher doses of chemotherapy use. Multiple ongoing clinical trials are investigating the potential therapeutic potential of SGLT-2 inhibitors in various types of cancer. CONCLUSION: More large-scale pre-clinical and clinical studies are needed to explore their potential preventive and therapeutic roles of SGLT-2 inhibitors in cancer treatment. In this narrative review, our aim is to explore the pre-clinical and clinical data regarding the potential anti-cancer effects of SGLT-2 inhibitors including the hypothetical pathophysiological mechanisms.

Physical exercise in kidney disease: A commonly undervalued treatment modality.

BACKGROUND: Physical inactivity has been identified as a risk factor for multiple disorders and a strong association exists between chronic kidney disease (CKD) and a sedentary lifestyle. Even though physical activity is crucial in the development and progression of disease, the general focus of the current medical practice is the pharmacological perspective of diseases with inadequate emphasis on lifestyle intervention. METHODS: In this narrative review we explain the pathophysiological mechanisms underlying the beneficial effects of physical exercise on CKD in addition to discussing the clinical studies and trials centred on physical exercise in patients with CKD. RESULTS: Physical activity influences several pathophysiological mechanisms including inflammation, oxidative stress, vascular function, immune response and macromolecular metabolism. While exercise can initially induce stress responses like inflammation and oxidative stress, long-term physical activity leads to protective countermeasures and overall improved health. Trials in pre-dialysis CKD patients show that exercise can lead to reductions in body weight, inflammation markers and fasting plasma glucose. Furthermore, it improves patients' functional capacity, cardiorespiratory fitness and quality of life. The effects of exercise on kidney function have been inconsistent in these trials. In haemodialysis, peritoneal dialysis and kidney transplant patients exercise interventions improve cardiorespiratory fitness, walking capacity and quality of life. Combined training shows the best performance to increase peak oxygen uptake in haemodialysis patients. In kidney transplant recipients, exercise improves walking performance, quality of life and potentially arterial stiffness. However, exercise does not affect glucose metabolism, serum cholesterol and inflammation biomarkers. Long-term, adequately powered trials are needed to determine the long-term feasibility, and effects on quality of life and major clinical outcomes, including mortality and cardiovascular risk, in all CKD stages and particularly in kidney transplant patients, a scarcely investigated population. CONCLUSION: Physical exercise plays a crucial role in ameliorating inflammation, oxidative stress, vascular function, immune response and macromolecular metabolism, and contributes significantly to the quality of life for patients with CKD, irrespective of the treatment and stage. Its direct impact on kidney function remains uncertain. Further extensive, long-term trials to conclusively determine the effect of exercise on major clinical outcomes such as mortality and cardiovascular risk remain a research priority.

Kidney and liver fat accumulation: from imaging to clinical consequences.

BACKGROUND: Recent studies indicate that accumulation of adipose tissue in various organs such as liver and kidney may contribute to the pathophysiology of metabolic syndrome. We aim to investigate the association between kidney and liver adipose tissue accumulation, assessed by the magnetic resonance imaging (MRI) proton density fat fraction technique, along with its relation to clinical and biochemical parameters. METHODS: We included 51 volunteers with phenotypical features of metabolic syndrome (mean age = 34 years, mean body-mass index = 26.4 kg/m2) in our study in which liver and kidney adipose tissue accumulation was assessed via MRI-proton density fat fraction along with multiple other clinical and biochemical parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio, serum lipid profile, liver function tests and body-mass index (BMI). RESULTS: Our results from the univariate linear regression analysis indicate that both the kidney and liver scores were positively correlated with markers such as BMI, urine albumin-to-creatinine ratio, triglycerides (p < 0.001) and negatively correlated with eGFR (p < 0.05). In multivariate analysis, urine albumin-to-creatinine ratio (p < 0.05), triglycerides (p < 0.01), eGFR (p < 0.05) and BMI (p < 0.001) were found to be independently associated with kidney and liver fat accumulation, respectively (R2 = 0.64; R2 = 0.89). There was also a positive correlation between kidney and liver fat accumulation. CONCLUSION: We have found a significant association between adipose tissue accumulation in liver and kidney and the parameters of metabolic syndrome. Moreover, the presence of a strong association between kidney and liver fat accumulation and kidney function parameters such as urine albumin-to-creatinine ratio and eGFR may be an indicator of the clinical significance of parenchymal fat accumulation.

Death and Venous Thromboembolism Analyses among Hospitalized COVID-19-Positive Patients: A Multicenter Study.

BACKGROUND: Coagulation disorders are frequently encountered among patients infected with coronavirus disease 2019 (COVID-19), especially among admitted patients with more severe symptoms. This study aims to determine the mortality rate and incidence and risk factors for venous thromboembolism (VTE) in hospitalized patients with COVID-19. METHODS: This retrospective observational cohort study was conducted from March to July 2020 using a hospital database. All adult patients (>18 years old) with laboratory-confirmed COVID-19 were included. Laboratory data and the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) for SARS-CoV-2 were obtained from medical records. The mortality rate and the incidence of VTE were established as study results. A multivariate logistic regression analysis was performed to identify predictors of thrombotic events. RESULTS: rA total of 1024 confirmed COVID-19 patients were treated, of whom 110 (10.7%) were deceased and 58 patients (5.7%) developed VTE. Death occurred more frequently in patients older than 50 years and those admitted to the intensive care unit (ICU, 95%) and who received mechanical ventilation (62.7%). Multivariate analysis revealed that cancer patients were two times more likely to have VTE (adjusted odds ratio = 2.614; 95% CI = (1.048-6.519); p = 0.039). Other chronic diseases, such as diabetes, hypertension, and chronic kidney disease, were not associated with an increased risk of VTE. CONCLUSIONS: One-tenth of hospitalized COVID-19 patients were deceased, and VTE was prevalent among patients with chronic conditions, such as cancer, despite anticoagulation therapy. Healthcare professionals should closely monitor individuals with a high risk of developing VTE to prevent unwanted complications.

Leading Causes of Chronic Kidney Disease Among Dialysis Patients in Al-Baha Region, Saudi Arabia.

Introduction Chronic kidney disease (CKD) and its progression to end-stage renal disease (ESRD) represent a growing health concern globally, with hypertension and diabetes commonly identified as primary etiological factors. This study evaluates the demographic and health profiles of individuals undergoing dialysis treatment in the Al-Baha region of Saudi Arabia, aiming to identify the predominant causes of ESRD and the associated socioeconomic and healthcare-related factors. Methodology This cross-sectional study analyzed data from patients receiving dialysis in Al-Baha. We assessed variables including etiology of ESRD, demographic data, presence of comorbid conditions, initial symptoms, and pre-dialysis health care engagement. Statistical analysis focused on the prevalence and correlations between the different variables and ESRD. The study also examined patients' educational background and employment status to ascertain ESRD's socioeconomic impact. Results The study found hypertension and diabetes as the leading causes of ESRD. Unknown etiologies accounted for 10.1% of cases, highlighting an area for further research. Notably, coronavirus disease 2019 (COVID-19) and cardiogenic shock emerged as potential new contributors, each representing 1.7% of cases. Most patients resided in urban areas, with the largest age group being 46 to 55 years. Men had a higher prevalence of ESRD than women. Low educational attainment was significant among patients, and unemployment due to ESRD was prevalent, pointing towards the need for vocational support. Clinical findings revealed late referrals to nephrologists, with a substantial proportion of diagnoses occurring in emergency settings. Family history suggested a higher-than-expected genetic component of CKD in the region. Conclusion The study confirms hypertension and diabetes as principal contributors to ESRD in Al-Baha while also pointing to the emergence of COVID-19 as a potential risk factor. Socioeconomic factors, including educational and employment status, are critical to patient management and outcomes. The high percentage of unknown etiologies and familial CKD prevalence warrants additional research. Improving early detection, enhancing patient education, and fostering timely nephrology consultations could mitigate the progression to ESRD and enhance patient quality of life.

Development, validation, and evaluation of allergic rhinitis symptoms and impact assessment (ARSIA) questionnaire.

INTRODUCTION: Allergic rhinitis (AR) is an inflammatory disease of the nasal mucosa. It is among the most common diseases globally and usually persists throughout life. Allergic Rhinitis and Its Impact on Asthma (ARIA) is a wellestablished guideline applicable to AR and was updated regularly since 2001, aiming to improve the care for AR patients. We proposed a new questionnaire that addresses the severity of allergic rhinitis symptoms, specifically nasal symptoms, and its impact on quality of life in terms of specific vital activities such as sleeping, working, school performance, leisure, or sport, based on the ARIA guideline. The objective was to develop, validate and evaluate Allergic Rhinitis Symptoms and Impact Assessment (ARSIA) questionnaire among allergic rhinitis patients in Hospital Sultan Abdul Halim, Sungai Petani (HSAH), and Hospital Universiti Sains Malaysia (HUSM). MATERIALS AND METHODS: This is a prospective observational study to develop, validate and evaluate the ARSIA questionnaire based on ARIA guidelines. The sample will be obtained from the list of patients under follow-up in the ORL clinic HSAH and HUSM with ages of 18 to 60 years, patients clinically diagnosed with allergic rhinitis, and with positive skin prick test. RESULTS: A total of 150 patients with a positive skin prick test participated in this study. In the 'nasal symptom' and 'impact on daily activities' domains, calculated Cronbach's alpha shows a value of 0.878 and 0.811 respectively. The inter-item correlation was calculated to analyse internal consistency reliability. Items B3 and B4 were dropped from the questionnaire as both showed a low correlation with other items. New Cronbach's alpha for the daily activities domain was 0.830, which showed better internal consistency reliability. All of the items were analysed for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Clinician diagnosis from the proforma was used as a comparison to the participant's responses. In the analysis, a cut-off points of 12 was used to classify the patient's nasal symptoms into intermittent or persistent, with a sensitivity of 75%, specificity of 86%, PPV of 95%, and NPV of 51%. Whereas, a cut-off point of 15 was used to classify the rhinitis impact on daily activities into mild or moderate/severe, with a sensitivity of 58%, specificity of 100%, PPV of 100%, and NPV of 42%. The only item in the 'control' domain has been dropped out following a consensus of experts and judgement as it has not been used in the clinician diagnosis and thus, is unable to test for sensitivity, specificity, PPV, and NPV. CONCLUSION: This newly developed, validated, and evaluated questionnaire is a good tool for the evaluation of allergic rhinitis symptoms and their impact on daily activities. It is important to understand that AR symptoms could have a significant impact on daily activities. Although further study and testing are needed, it provides an initial means for evaluating the patient condition and control level, as well as patients' perception of their rhinitis control.

Awareness of pelvic organ prolapse and attitude towards its treatment among Malaysian women.

INTRODUCTION: The aim of this study is to determine the level of awareness of pelvic organ prolapse (POP) and factors that influence the attitude towards the treatment of POP among Malaysian women. MATERIALS AND METHODS: This was a cross-sectional study of 400 women from registered non-government organisations (NGOs) in Malaysia who voluntarily answered questionnaires distributed through Google form via emails. Data were analysed using descriptive statistics, independent t-test and one-way ANOVA test. RESULTS: Four hundred respondents participated in this study. The mean age was 40.42 years old (SD=12.566). The mean score for the studied population was 4.96 (SEM 0.124). Only 58 (14.5%) respondents obtained a score of eight or more, and 235 (58.8%) respondents scored between 4 and 7. The rest of 107 (26.7%) respondents scored 3 and less. There were statistically significant differences in the mean score for level of awareness between marital statuses, menopausal status, number of children and occupation. There were only 273 (68%) respondents who will seek treatment if they experience symptoms of POP. The most frequent reasons for not seeking treatment were unawareness of the availability of medical treatment for POP (69 %). CONCLUSION: Majority of the respondents have an inadequate level of awareness on POP. Although more than half of the respondents will seek treatment if they experience symptoms of POP, concerns raised by those who chose not to seek treatment should be addressed by a more effective public awareness programme. This includes the unawareness of the availability of medical treatment and the embarrassment to see medical practitioners.

Physiological effects of exercise in heat while wearing a polyester versus cotton T-shirt in physically active men with obesity: a pilot study.

BACKGROUND: Obesity may impair evaporation especially during exercising in heat. Polyester sportwear is proposed to improve the evaporation but its effectiveness remains overlooked. We investigated physiological effects of exercise in heat while wearing a polyester versus cotton T-shirt on thermoregulation, perspiration, and cardiovascular regulations. METHODS: Physically active men with obesity (N.=7; 21.7±1.7 years old; VO2peak 36.8±8.7 mL/kg/min; body fat percentage 34.7±4.3%) performed two randomized, crossover walking sessions for 30 mins (27 °C; 12% relative humidity) while wearing a polyester or cotton T-shirt, separated by a 7-day wash out period. Thermoregulation was assessed by measuring tympanic, torso (back and chest), and peripheral (forehead and forearm) skin temperatures. Perspiration rate was estimated as the difference in body weight (pre minus post walking). Heart rate was measured by a Polar heart rate monitor. Systolic and diastolic blood pressure were measured by a sphygmomanometer. All measurements were performed pre, during, and post each session. Two-way ANOVA examined main effects of time, fabric type, and their interactions on the study's outcomes. RESULTS: Back and chest temperatures increased (∆=1.6 °C and 0.9 °C, respectively) while forehead and forearm temperatures decreased (∆=-0.5 °C and -1.6 °C, respectively) over time (P<0.05 for all). Only forehead temperature had an interaction effect for time by fabric type where greater decrease was observed during the polyester T-shirt session compared to the cotton T-shirt session (∆=-0.1 vs. -0.8 °C; P=0.016). Heart rate (∆=27.8 beat/min) and systolic blood pressure (∆=7.5 mmHg) increased while diastolic blood pressure (∆=-5.0 mmHg) decreased over time (P<0.05 for all). No difference observed for perspiratory rate (P>0.05). CONCLUSIONS: The current findings do not support the superiority of polyester or cotton sportwear for better thermoregulatory, perspiratory, and cardiovascular regulations in physically active men with obesity. Future research should examine the effectiveness of other alternative fabrics of sportwear for better physiological responses when exercising in the heat, particularly in adults with obesity.

Bladder Sparing Extirpation of Pelvic Mass With Ureteral Reimplantation: A Case Report on Pelvic Lipomatosis Treatment.

Pelvic lipomatosis is a proliferative disease characterised by excessive fat growth in retroperitoneal space leading to inadequate bladder drainage and ureteral compression. Cystitis glandularis, cystitis cystica, or cystitis follicularis can be found in the majority of patients with the disease. We report a case of a 63-year-old man diagnosed outside our hospital with pelvic lipomatosis after finding a pelvic mass behind the bladder causing severe bilateral hydronephrosis. A bladder-sparing excision of the pelvic lipomatosis mass with bilateral ureteric reimplantation was performed, thereby avoiding the need for urinary diversion. Our case supports the hypothesis that pelvic fat mass extirpation and ureteral reimplantation is an effective surgical treatment strategy for pelvic lipomatosis.

Muslim perspectives on palliative care in perinatal and neonatal patients: a mini-review.

Muslims comprise nearly a quarter of the worldwide population, with significant populations in the United States, Canada, and Europe. As clinicians, it is important to be familiar with Islamic religious and cultural perspectives on medical treatment, life-prolonging measures and comfort and palliative care, but historically, this has been a gap in the literature. Recently, there have been multiple papers discussing Islamic bioethics, particularly in regards to end of life care in adults; however, there has been a lack of literature discussing the Islamic perspective on issues related to neonatal and perinatal end of life care. This paper uses clinical scenarios to review key relevant principles of Islamic law, discussing the primary and secondary sources used in formulating fatawa, including the Quran, hadith, qiyas, and 'urf, and the importance of preservation of life and upholding of human dignity (karamah). Neonatal and perinatal scenarios are used to specifically explore the Islamic perspective on withholding and withdrawal of life-sustaining measures and determining what constitutes an acceptable quality of life. In some Islamic cultures the expertise of the patient's physician is given significant weight in making these judgments, and as such, families may appreciate frank assessment of the situation by the clinical team. Because of the various factors involved in issuing religious ruling, or fatwa, there is a wide spectrum of opinions on these rulings, and physicians should be aware of these differences, seek counsel and guidance from local Islamic leaders, and support families in their decision-making process.

Intrauterine life to adulthood: a potential risk factor for chronic kidney disease.

Multiple risk factors for chronic kidney disease (CKD), one of the major causes of morbidity and mortality in the adult population globally, have been identified, including older age, male gender, family history, smoking, diabetes mellitus, hypertension, ischaemic heart diseases and various medications. Preterm delivery, affecting >10% of the newborns in the USA, is a global concern with increasing incidence in recent decades. Preterm birth has been linked to multiple medical comorbidities such as diabetes mellitus, hypertension and cardiovascular diseases, while its association with CKD has recently been investigated. Prematurity and intrauterine growth restriction (IUGR) have been associated with an increased risk for CKD, specific histopathological examination findings and CKD-associated risk factors such as diabetes mellitus, hypertension and dyslipidaemia. In this narrative review, our aim is to evaluate and summarize the association between the risk for CKD and prematurity, low birthweight and IUGR along with potential underlying pathophysiological mechanisms.

Paradoxical Associations of Occupational and Nonoccupational Sedentary Behavior With Cardiovascular Disease Risk Measures in Desk Workers.

OBJECTIVES: We assessed sedentary behavior (SB) patterns and examined its associations, by domain, with cardiovascular disease (CVD) risk measures in desk workers ( N = 273). METHODS: Sedentary behavior was measured by activPAL3 and partitioned into occupational and nonoccupational SB. Cardiovascular disease risk measures included blood pressure, pulse wave velocity, heart rate, and heart rate variability. Paired t tests evaluated patterns of SB across domains. Linear regressions estimated associations of occupational and nonoccupational SB with CVD risk measures. RESULTS: Participants spent 69% of their time in SB; higher proportions were accumulated during occupational versus nonoccupational time. Higher all-domain SB was only associated with higher pulse wave velocity. Paradoxically, greater nonoccupational SB unfavorably associated with CVD risk measures, while higher occupational SB favorably correlated to CVD risk measures. CONCLUSIONS: Observed paradoxical associations suggest that domain should be considered in efforts to improve cardiovascular health by reducing SB.

The Impact of a Patient Participating in Evaluating Patient Safety by Using the Patient Measure of Safety in Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Patient safety is an essential element for delivering quality of healthcare. Many studies focus on measuring patient safety from the healthcare provider's perspective to improve patient safety in healthcare facilities. However, patient participation may reduce medical errors and improve patient safety by providing information regarding the safety of their care. This study aimed to evaluate patient safety from the inpatients' perspective and the extent of the influence of the sociodemographic factors on their assessment. METHODS: A cross-sectional study was conducted at hospitals in different Saudi Arabian regions with 1569 inpatient adults 18 years of older who voluntarily completed an online questionnaire using the Patient Measure of Safety tool (Arabic translated). Two questions were added to assess patient feedback about the overall perception of safety and witnessing patient safety events. COVID-19 patients and those with a mental disorder or incapable of providing informed consent were excluded. RESULT: The total number of participants was 1569 inpatients from 17 hospitals. Sixty-one percent of the participants were female, and 41.62% were from the 18- to 35-year age group. Less than half (38.69%) of patients stayed at the hospital between 3 and 5 days. Percentages of positive responses were more than 90% observed in dignity and respect, communication and teamworking, and organization and care planning domains. Percentages of negative responses were more than 20% found in organization and care planning, access to resources, and ward type and layout domains. Among the respondents, 57.3% (n = 899) rated the safety of their wards as excellent as opposed to 2.9% (n = 46) who rated it as poor. Approximately 5% (n = 79) have noticed 1 event, and 2.3% (n = 36) have noticed 2 or 3 events. Unemployed participants had a significantly lower rate of positive responses in domains of communication, access to resources, and ward type. In contrast, the no-schooling group had a significantly greater rate of negative responses in care planning and ward-type domains. CONCLUSIONS: The patient plays a key role in enhancing the quality of care and has the potential to detect adverse events. The study highlighted the need to focus on better communication processes for patients with low education levels to enhance their engagement in their care. Further steps should be taken to understand the extent of the patient's involvement in the improvement that could be tackled from feedback on the safety of care.

Uncovering a novel role of focal adhesion and interferon-gamma in cellular rejection of kidney allografts at single cell resolution.

Background: Kidney transplant recipients are currently treated with nonspecific immunosuppressants that cause severe systemic side effects. Current immunosuppressants were developed based on their effect on T-cell activation rather than the underlying mechanisms driving alloimmune responses. Thus, understanding the role of the intragraft microenvironment will help us identify more directed therapies with lower side effects. Methods: To understand the role of the alloimmune response and the intragraft microenvironment in cellular rejection progression, we conducted a Single nucleus RNA sequencing (snRNA-seq) on one human non-rejecting kidney allograft sample, one borderline sample, and T-cell mediated rejection (TCMR) sample (Banff IIa). We studied the differential gene expression and enriched pathways in different conditions, in addition to ligand-receptor (L-R) interactions. Results: Pathway analysis of T-cells in borderline sample showed enrichment for allograft rejection pathway, suggesting that the borderline sample reflects an early rejection. Hence, this allows for studying the early stages of cellular rejection. Moreover, we showed that focal adhesion (FA), IFNg pathways, and endomucin (EMCN) were significantly upregulated in endothelial cell clusters (ECs) of borderline compared to ECs TCMR. Furthermore, we found that pericytes in TCMR seem to favor endothelial permeability compared to borderline. Similarly, T-cells interaction with ECs in borderline differs from TCMR by involving DAMPS-TLRs interactions. Conclusion: Our data revealed novel roles of T-cells, ECs, and pericytes in cellular rejection progression, providing new clues on the pathophysiology of allograft rejection.

An update review on hemodynamic instability in renal replacement therapy patients.

BACKGROUND: Hemodynamic instability in patients undergoing kidney replacement therapy (KRT) is one of the most common and essential factors influencing mortality, morbidity, and the quality of life in this patient population. METHOD: Decreased cardiac preload, reduced systemic vascular resistance, redistribution of fluids, fluid overload, inflammatory factors, and changes in plasma osmolality have all been implicated in the pathophysiology of hemodynamic instability associated with KRT. RESULT: A cascade of these detrimental mechanisms may ultimately cause intra-dialytic hypotension, reduced tissue perfusion, and impaired kidney rehabilitation. Multiple parameters, including dialysate composition, temperature, posture during dialysis sessions, physical activity, fluid administrations, dialysis timing, and specific pharmacologic agents, have been studied as possible management modalities. Nevertheless, a clear consensus is not reached. CONCLUSION: This review includes a thorough investigation of the literature on hemodynamic instability in KRT patients, providing insight on interventions that may potentially minimize factors leading to hemodynamic instability.

The risk for chronic kidney disease in metabolically healthy obese patients: A systematic review and meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is associated with obesity and metabolic syndrome. Nevertheless, the association of CKD with phenotype referred as metabolically healthy obese or overweight is unclear. In this this systematic review and meta-analysis, we investigate the relationships between obesity and CKD independent of metabolic syndrome by appraising published evidence in studies focusing on metabolically healthy obese people. MATERIALS AND METHODS: We performed a literature search through three databases Embase (Elsevier), the Cochrane Central Register of Controlled Trials (Wiley) and PubMed/Medline Web of Science up to March 2022 with the following terms: "chronic kidney disease", "kidney function", "obesity", "metabolic syndrome", "metabolically healthy obesity", "metabolically healthy overweight". Metabolically unhealthy was defined an individual having at least 3 of the following: abdominal obesity, high blood pressure, hypertriglyceridemia, low HDL cholesterol and hyperglycaemia. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for reporting. Prospective, retrospective, randomized and nonrandomized studies fitting the search criteria were included in our results. RESULTS: Our final analysis included 16 studies with a total number of 4.965.285 participants. There is considerable heterogeneity in terms of study design, participant characteristics and number of participants across individual studies. In comparison to healthy normal weight patients, the risk was progressively higher in overweight (RR 1.29, 95% CI 1.27 to 1.32, p < 0.001) and obese patients (RR 1.47, 95% CI 1.31 to 1.65, p < 0.001). CONCLUSION: Metabolically healthy overweight and obese individuals have higher risk of CKD compared to individuals without weight excess.

A Comparative Investigation Applying Testicular Fine Needle Aspiration Cytology and Open Testicular Biopsy Histology for the Diagnosis of Azoospermia and Severe Oligospermia.

Open testicular biopsy histology and fine needle aspiration cytology (FNAC) are the most popular tests used to diagnose male infertility. This study aimed to assess the cytological characteristics of 186 infertile males aged 24-63 with testicular FNAC. Furthermore, the existing relationship between males with severe oligospermia (sperm count: 5 million/ml) and azoospermia was investigated via both cytological and histological diagnosis methods. With a 1.5-inch and 25-gauge needle, the testis was aspirated from three locations (the upper, middle, and lower poles). Papanicolaou stain or Giemsa stain was used to make smears on albumenized slides, which were then dried in the air and stained. A biopsy of the testicles was performed there, preserved in Bouins solution, processed as usual, and stained with hematoxylin and eosin stain. According to our findings, 66.7% of patients had secondary maturation arrest, whereas 18.3% and 15.1% of them had hypospermatogenesis and Sertoli cell only (SCO). Results of the comparison showed that both procedures were very similar. According to biopsy histological examinations, only 3 (1.6%) of the 28 normal FNAC instances had hypospermatogenesis with lymphocyte infiltration. The majority of SCO patients were over 50 years old. These findings revealed that FNAC is more effective than testicular histology for the assessment of male infertility.