Translation, cross-cultural adaptation, and psychometric properties of the Arabic version of the MedRisk instrument for measuring patient satisfaction with physical therapy care.

PURPOSE: This study aimed to translate, cross-culturally adapt, and validate the MedRisk Instrument for Measuring Patient Satisfaction with Physical Therapy Care into Arabic (MRPS-Ar). MATERIALS AND METHODS: The 20-Item MRPS was translated and cross-culturally adapted into Arabic following international guidelines. Patients (n = 229) with musculoskeletal conditions who received physical therapy care completed the MRPS-Ar and global rating of change scale. Of these patients, 95 completed the MRPS-Ar twice. Factor structure, floor and ceiling effects, internal consistency, test-retest reliability, and construct validity of the MRPS-Ar were evaluated. RESULTS: Principal component analysis suggested 3-factor solution: a 7-item facility experience, 6-item therapeutic experience, and 3-item positive experience. The MRPS-Ar and its factors showed acceptable internal consistency (Cronbach's alpha coefficients ranged from 0.819 to 0.936) and excellent test-retest reliability (ICCs ranged from 0.965 to 0.983). The global measures of satisfaction were significantly correlated with the global rating of change (Spearman's rho = -0.678, p < 0.001 for item "overall satisfaction" and Spearman's rho = -0.690, p < 0.001 for item "would return"). CONCLUSIONS: The 18-item MRPS-Ar displayed adequate psychometric properties for measuring patients' satisfaction with physical therapy care. The MRPS-Ar is a reliable and valid instrument that can be used in medical, clinical, and research fields.

Comparative diagnostic efficacy of cranial CT, CTA, and DSA in subarachnoid hemorrhage management: A systematic review and meta-analysis.

INTRODUCTION: Subarachnoid hemorrhage (SAH) is a critical medical condition associated with high morbidity and mortality rates. Timely and accurate diagnosis is crucial for optimal patient outcomes. Cranial computed tomography (CT), computed tomography angiography (CTA), and digital subtraction angiography (DSA) are commonly used imaging modalities for diagnosing SAH, but their comparative diagnostic efficacy remains debated. METHODS: A systematic review and meta-analysis was conducted to evaluate the diagnostic performance of cranial CT, CTA, and DSA in identifying SAH. PubMed, Google scholar, Cochrane Library databases were searched for relevant studies published up to January 2024. Pooled sensitivity, specificity, and the summary receiver operating characteristic (SROC) curve were calculated using Review Manager 5.4. RESULTS: A total of 31 studies involving 10,287 patients were included in the analysis. The pooled sensitivity of cranial CT for detecting SAH was 94.7 % (95 % Confidence Interval, CI) with a specificity of 98.3 % (95 % CI). CTA demonstrated a pooled sensitivity of 94.1 % (95 % CI) and specificity of 93.4 % (95 % CI). DSA showed a pooled sensitivity of 87.7 % (95 % CI) and specificity of 95.8 % (95 % CI). The SROC curve demonstrated discriminatory ability for all modalities. CONCLUSION: Cranial CT, CTA, and DSA are valuable imaging modalities for diagnosing SAH, with high sensitivity and specificity. Cranial CT serves as an initial screening tool, while CTA offers superior sensitivity in detecting aneurysmal SAH. DSA remains essential in specific clinical scenarios. Further prospective studies are needed to validate these findings and refine diagnostic guidelines for SAH.

The mediating role of learning motivation in the relationship among perceived stress and emotional regulation among Saudi nursing students in clinical practice.

BACKGROUND: Nursing students often face high levels of stress due to demanding responsibilities during clinical placement. Emotional regulation, the ability to manage and regulate one's emotions effectively, is crucial for nursing students in dealing with stress and maintaining their overall well-being. Additionally, learning motivation plays a vital role in students' engagement and academic success. The current investigation aimed at studying the link that exists among stress, learning motivation, and emotional regulation among Saudi undergraduate nursing students. The study also aimed at investigating the sequential mediating effects that motivation might perform in this association. METHODS: A quantitative cross-sectional methodology was used in the present research, which recruited 367 Saudi undergraduate nursing students. RESULTS: The results of the ANOVA showed that the level of perceived stress was linearly and negatively correlated with emotional regulation and motivation. Upon conducting structural equation modeling, significant direct and indirect effect pathways were identified between perceived stress, emotional regulation, and motivation, while only indirect pathways were identified between perceived stress and emotional regulation. CONCLUSIONS: This study provides evidence of the mediating role of learning motivation in the relationship between perceived stress and emotional regulation among Saudi nursing students. The results highlight the negative impact of stress on emotional regulation and learning motivation and emphasize the importance of addressing motivational factors in interventions aimed at enhancing emotional regulation among nursing students.

Current views on preoperative rehabilitation practice after anterior cruciate ligament injury among licensed physical therapists in Saudi Arabia: An online-based cross-sectional survey.

Preoperative rehabilitation is an important stage to both physically and mentally prepare patients for anterior cruciate ligament reconstruction (ACLR) and postoperative rehabilitation. This study aimed to investigate the current preoperative rehabilitation practice after anterior cruciate ligament injury among licensed physical therapists in Saudi Arabia. This was an online-based cross-sectional survey. A total of 114 physical therapists completed the survey. The survey consisted of 16 mandatory questions about management strategies, prescribed exercises, patients' physical and psychological concerns, and discussions about nonoperative management. The majority of the respondents used the following preoperative interventions: education (89.5%), closed kinetic chain exercises (66.7%), stretches (63.2%), open kinetic chain exercises (61.4%), proprioceptive exercises (59.6%), cold (56.1%), and activity modification advice (52.6%). More than half of the respondents would recommend patients awaiting ACLR to complete the exercises 2 to 4 times weekly (56.1%) for up to 8 weeks (80.7%) before ACLR. The respondents (73.7%) reported that patients awaiting ACLR did not receive preoperative rehabilitation due to 2 primary factors: the orthopedic team did not refer patients to rehabilitation specialists, and there was a lack of awareness about preoperative rehabilitation. Most therapists (86%) would discuss conservative management if a patient returned to their preinjury level of function before surgery. The surveyed physical therapists reported using various interventions and preoperative rehabilitation lengths with patients awaiting ACLR. The majority of the therapists indicated that patients awaiting ACLR did not receive preoperative rehabilitation. Future studies are needed to establish a consensus on the optimal preoperative rehabilitation program.

Inflammation-based scores in patients with pheochromocytoma.

BACKGROUND: Pheochromocytoma is associated with systemic inflammation, but the underlying mechanisms are unclear. Therefore, we investigated the relationship between plasma metanephrine levels and haematological parameters - as a surrogate of inflammation - in patients with pheochromocytoma and the influence of preoperative α-blockade treatment. DESIGN AND METHODS: We retrospectively studied 68 patients with pheochromocytoma who underwent adrenalectomy (median age 53 years, 64.7% females) and two control groups matched for age, sex, and body mass index (BMI): 68 patients with non-functioning adrenocortical tumors (NFAT) and 53 with essential hypertension (EAH). The complete blood count (CBC) and several inflammation-based scores [Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR), Systemic-Immune-Inflammation Index (SII), Prognostic-Nutrition Index (PNI)] were assessed in all patients and, in a subset of pheochromocytomas, after adrenalectomy (n=26) and before and after preoperative α-blockade treatment (n=29). RESULTS: A higher inflammatory state, as indicated by both CBC and inflammation-based scores, was observed in patients with pheochromocytoma compared to NFAT and EAH. Plasma metanephrine levels showed a positive correlation with NLR (r=0.4631), PLR (r=0.3174), SII (r=0.3709), and a negative correlation with LMR (r=0.4368) and PNI (r=0.3741), even after adjustment for age, sex, ethnicity, BMI and tumor size (except for PLR). After adrenalectomy, we observed a reduction in NLR (p=0.001), PLR (p=0.003), SII (p=0.004) and a concomitant increase in LMR (p=0.0002). Similarly, α-blockade treatment led to a reduction in NLR (p=0.007) and SII (p=0.03). CONCLUSIONS: Inflammation-based scores in patients with pheochromocytoma showed pro-inflammatory changes that correlated with plasma metanephrine levels and are ameliorated by adrenalectomy and α-blockade.

Survival outcomes after using charged particle radiotherapy as a treatment modality for gliomas: A systematic review and meta-analysis.

INTRODUCTION: Charged particle therapy is an emerging radiation treatment for a number of tumors; however, more research is needed to determine its safety and efficacy when treating intra-axial brain tumors (commonly known as gliomas). The overall survival of patients treated with charged particle radiation versus those receiving photon therapy were compared in this systematic review and meta-analysis. METHODS: The databases used as part of the search strategy were the following: MEDLINE (PubMed), Google Scholar, Scopus, and Cochrane. The search was conducted in order to find pertinent clinical studies. A random-effect meta-analysis was used to generate pooled estimates of overall survival at 1,3, and 5 years. RESULTS: Nineteen studies with a total of 1140 patients were included in this meta-analysis. Following treatment, the patient's follow-up period lasted 44.4 months (range: 14.3 - 91.2 months). At one year (relative risk 1.17, 95% CI 1.07 - 1.28; p = 0.049), three years (relative risk 1.73, 95% CI 1.41 - 2.12; p = 0.001), and five years (relative risk 2.00, 95% CI 1.52 - 2.63; p = 0.005), charged particle radiotherapy had a significantly higher pooled overall survival than photon therapy. CONCLUSION: Charged particle therapy could be associated with better clinical outcomes for patients with gliomas compared to photon therapy. More prospective randomized trials and comparative studies are strongly encouraged to enable accurate meta-analysis and a better exploration of prognosis.

Stress and academic engagement among Saudi undergraduate nursing students: The mediating role of emotion regulation and emotional intelligence.

AIM: To assess the mediating role of emotion regulation and emotional intelligence in the relationship between stress and academic engagement among Saudi undergraduate nursing students. DESIGN: This study employed a quantitative cross-sectional research design. METHODS: The study recruited 367 Saudi undergraduate nursing students at a major Saudi university. Structural equation modelling was used to explore the mediational model. RESULTS: The results of the ANOVA and Welch F-test demonstrated that the emotional intelligence, emotional regulation and academic engagement scores were statistically significantly different according to stress levels (p-values <0.01). Perceived stress has a statistically significant moderate negative correlation with academic engagement and emotional intelligence and a strong negative correlation with emotional regulation. The results also showed that academic engagement had a statistically significant moderate positive association with emotional intelligence and emotional regulation. Results indicate that stress and academic engagement are negatively correlated among Saudi undergraduate nursing students. It focuses on the balancing functions of emotional regulation and emotional intelligence, highlighting their ability to lower stress levels and improve academic engagement. No Patient or Public Contribution.

PET/CT in comparison with PET/MRI as an imaging modality in the management of Gliomas-A systematic review and meta analysis.

INTRODUCTION: Gliomas are the most commonly occurring type of primary brain tumors. They account for 32% of all brain tumors and 80% of all malignant intracranial tumors. Gliomas are separated into four grades according to the World Health Organization. While low-grade gliomas generally have a favorable outlook, high-grade gliomas cause significant morbidity and mortality Given the lack of clarity about the causes of gliomas and their potential lethality, early diagnosis and identification is crucial. METHODS: The systematic literature search was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The electronic databases used were the following: Google Scholar, MEDLINE (PubMed), and EMBASE, and Cochrane Library. Medical subject headings (MeSH) and Boolean operators were used to find any relevant literature. To evaluate the quality of the studies used, a quality assessment was performed using the QUADAS-2. RESULTS: Four papers concerning the PET/MR modality that included 122 patients while on the other hand we had five papers about the PET/CT modality that included 251 patients. On both sides, the patients were mostly male and the overall mean age 45 ±â€¯10 years. The overall sensitivity and specificity of the PET/MR modality was found to be 89% (95% CI, p = 1.00) and 84% (95% CI, p = 1.00) respectively. In the four included studies revolving around PET/MR, the accuracy was found out to be: 78%, 96.4%, 100%, and N/R. CONCLUSION: The PET/MR modality was deemed to be slightly diagnostically better than the PET/CT modality. More studies investigating the efficacy of using hybrid FDG PET/MR in gliomas are encouraged to shed light on its potential role in clinical use. Conducting prospective randomized studies that directly compare the sensitivity and specificity of PET/CT and PET/MR for glioma would help establish the role of imaging modalities for diagnosis of glioma.

Does early stable fixation reduce complications in paediatric femoral neck fractures?

The primary objective of this study was to juxtapose the union rate and incidence of complications in paediatric patients presenting early (≤ 7 days) following injury with children presenting later (> 7 days) with femoral neck fractures. This critical appraisal evaluated 15 patients according to their timing of presentation and surgery from the initial day of injury (Group A: operated ≤ 7 days or Group B: > 7 days of injury). Patients with traumatic femoral neck fractures with Delbet 1 to 4 subtypes who were skeletally immature (age ≤ 16 years) were included in the study. Pathological fractures and post-infective fractures were not included. Each patient's secondary loss of reduction was calculated by measuring the Neck shaft angle (NSA) on the immediate post-operative radiograph and at the union. A change in NSA of ≥ 5 degrees was considered a significant loss of reduction. Ratliff's Criteria was used to analyze the final result, and a thorough record of complications was kept. There were no significant variations in the two groups' with respect to distributions of age, sex, injury mechanism, or fracture pattern. The most frequent injury culprit in both groups was falling from a height. Type II fracture pattern (54.54%) was more common in group A, while Type III and Type II fracture pattern was equally distributed in group B. In group A, the mean operation time was 55 ± 8.25 minutes, whereas in group B, it was 65 ± 15 minutes (p-value > 0.05). In group A, 90.9% of patients underwent CCS fixation, and in group B, 75% underwent fixation by CCS. The quality of reduction in post-operative radiographs was anatomical in 10 (90.9%) patients and unacceptable in 1 (9.1%) patient. In group B, 2 (50%) patients had an anatomical reduction, while 2 (50%) patients had an unacceptable reduction. Timing of reduction and its association with complications showed that early stable reduction and fixation decrease the occurrence of complications in femoral neck fractures (p-value = 0.033). Fracture union was seen in all our patients in both groups and none of our patients underwent non-union. The mean union time was 11.11 ± 7.06 weeks in group A and 16.5 ± 2.59 weeks in group B (p-value = 0.0189). In group A, only 1 (9.1%) patient developed coxa vara. In group B, out of 4 patients, the femoral head of one patient underwent avascular necrosis, one patient exhibited coxa vara, and 1 patient developed premature physeal closure with limb length inequality. Management of femoral neck fractures in children is challenging because of the paediatric bone's peculiar anatomic and physiological considerations. In our study, patients operated within 7 days developed fewer complications as compared to patients who were operated after 7 days, which was statistically significant. Although AVN is a frequent adverse consequence of pediatric femoral neck fractures, early reduction and stable fixation lowers AVN rates, as observed in our study. Our short-term functional and radiological results using the Ratliff scoring system were comparable to previous studies owing to stable anatomic reduction. Based on our findings and the existing literature, we emphasize long-term follow-up and recommend an early stable anatomic reduction in the treatment of paediatric femoral neck fractures.

Service evaluation suggests variation in clinical care provision in adults with congenital adrenal hyperplasia in the UK and Ireland.

BACKGROUND: Congenital adrenal hyperplasia (CAH) encompasses a rare group of autosomal recessive disorders, characterised by enzymatic defects in steroidogenesis. Heterogeneity in management practices has been observed internationally. The International Congenital Adrenal Hyperplasia registry (I-CAH, https://sdmregistries.org/) was established to enable insights into CAH management and outcomes, yet its global adoption by endocrine centres remains unclear. DESIGN: We sought (1) to assess current practices amongst clinicians managing patients with CAH in the United Kingdom and Ireland, with a focus on choice of glucocorticoid, monitoring practices and screening for associated co-morbidities, and (2) to assess use of the I-CAH registry. MEASUREMENTS: We designed and distributed an anonymised online survey disseminated to members of the Society for Endocrinology and Irish Endocrine Society to capture management practices in the care of patients with CAH. RESULTS: Marked variability was found in CAH management, with differences between general endocrinology and subspecialist settings, particularly in glucocorticoid use, biochemical monitoring and comorbidity screening, with significant disparities in reproductive health monitoring, notably in testicular adrenal rest tumours (TARTs) screening (p = .002), sperm banking (p = .0004) and partner testing for CAH (p < .0001). Adoption of the I-CAH registry was universally low. CONCLUSIONS: Differences in current management of CAH continue to exist. It appears crucial to objectify if different approaches result in different long-term outcomes. New studies such as CaHASE2, incorporating standardised minimum datasets including replacement therapies and monitoring strategies as well as longitudinal data collection, are now needed to define best-practice and standardise care.

Circulating cell-free DNA-based biomarkers for prognostication and disease monitoring in adrenocortical carcinoma.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. The aim of the study was to investigate the role of circulating cell-free DNA (ccfDNA)-related biomarkers (BMs) for prognostication and monitoring of ACC. DESIGN AND METHODS: We investigated 34 patients with ACC and 23 healthy subjects (HSs) as controls. Circulating cell-free DNA was extracted by commercial kits and ccfDNA concentrations were quantified by fluorimeter (BM1). Targeted sequencing was performed using a customized panel of 27 ACC-specific genes. Leucocyte DNA was used to discriminate somatic variants (BM2), while tumour DNA was sequenced in 22/34 cases for comparison. Serial ccfDNA samples were collected during follow-up in 19 ACC patients (median period 9 months) and analysed in relationship with standard radiological imaging. RESULTS: Circulating cell-free DNA concentrations were higher in ACC than HS (mean ± SD, 1.15 ± 1.56 vs 0.05 ± 0.05 ng/µL, P < .0001), 96% of them being above the cut-off of 0.146 ng/µL (mean HS + 2 SD, positive BM1). At ccfDNA sequencing, 47% of ACC showed at least 1 somatic mutation (positive BM2). A combined ccfDNA-BM score was strongly associated with both progression-free and overall survival (hazard ratio [HR] = 2.63; 95% CI, 1.13-6.13; P = .010, and HR = 5.98; 95% CI, 2.29-15.6; P = .0001, respectively). During disease monitoring, positive BM2 showed the best specificity (100%) and sensitivity (67%) to detect ACC recurrence or progress compared with BM1. CONCLUSION: ccfDNA-related BMs are frequently detected in ACC patients and represent a promising, minimally invasive tool to predict clinical outcome and complement surveillance imaging. Our findings will be validated in a larger cohort of ACCs with long-term follow-up.

Ipsilateral versus contralateral static endurance- balance abilities among healthy college students.

Objectives: This study sought to determine the association and the difference, if any, between the levels of the contralateral and between the levels of the ipsilateral sides during static endurance-balance exercise. Methods: One hundred twelve healthy active- college students (55 females and 57 males) participated in this cross-sectional study. Each participant performed the contralateral (raising one arm and opposite-side leg) quadruped bird dog exercise and balanced in static condition. Side bridge exercise was performed from lying on your side then engaging your core muscles and lifting your upper body and hips off the ground, maintaining a straight line and holding this position as long as tolerated. Results: Wilcoxon signed rank test showed significant difference (p = 0.004) between the contralateral right and left quadruped bird dog but insignificant difference (p = 0.059) between the ipsilateral right and left side bridge endurance-balance exercises. Mann-Whitney U test showed that the holding time was significant across gender for the contralateral but was insignificant for the ipsilateral endurance-balance exercise. Mann-Whitney U test was insignificant (p > 0.05) between those being recreationally active or inactive. Kruskal-Wallis test revealed insignificant difference between body mass index categories. Spearman's rho correlation coefficient showed strong positive correlation equals 0.85 and 0.75 (p < 0.001) of the contralateral quadruped bird dog and the ipsilateral side bridge exercises respectively. Conclusions: A significant difference was observed for contralateral, while no significant difference was found for ipsilateral endurance-balance abilities. Therefore, clinicians and rehab specialist should consider these findings when assessing the endurance-balance abilities to properly devise appropriate exercise progression of different trunk stabilizers.

Healthcare policies, precautionary measures and outcomes of mass gathering events in the era of COVID-19 pandemic: Expedited review.

With the onset of the COVID-19 pandemic in early 2020, several countries suspended or restricted mass gathering (MG) events to mitigate the risk of superspreading events. Prohibiting MGs aimed to lessen the likelihood of highly infectious persons coming into close contact with many others. Now that the world has opened its doors wide and removed most of precautionary measures, many questions arise. In this review, we aimed to summarize the current evidence regarding the policies and regulations that were implemented for the safe return of MG events. Besides, we highlighted the impact of the return of MG events during 2021 on the trajectory of COVID-19 spread. Canceling MG events can carry religious, societal, economic, and public negative consequences necessitating the safe return of these events. The experience with the COVID-19 pandemic was the foundation for the recommendations for the safe conduction of MG events during the pandemic by international public health bodies. When policymakers adequately applied precautionary measures and strategic approaches, we witnessed the safe holding of huge MG events without aggravating the COVID-19 situation or increasing the number of new cases beyond the capacity and readiness of the national healthcare system.

Current Rehabilitation Practices and Return to Sports Criteria After Anterior Cruciate Ligament Reconstruction: A Survey of Physical Therapists in Saudi Arabia.

CONTEXT: With the high prevalence of anterior cruciate ligament rupture among young and active individuals, rehabilitation after the injury and surgery should meet the current evidence-based recommendations to restore knee function and reduce the risk of further injury. This study aimed to investigate the current rehabilitation practices and return to sports (RTS) criteria after anterior cruciate ligament reconstruction (ACLR) among physical therapists in Saudi Arabia. DESIGN: Online cross-sectional survey-based study. METHODS: A total of 177 physical therapists in Saudi Arabia participated in this survey. The survey included questions about the preferred postoperative timing and frequency of rehabilitation, current views on the importance of preoperative and postoperative rehabilitation to the overall outcomes, the timeframe of RTS, and the decision-making process to RTS. RESULTS: Most therapists (96.6%) believed preoperative rehabilitation was essential/important to postoperative outcomes. Two-thirds encouraged patients to start rehabilitation program within 1 to 4 days immediately post-ACLR. RTS was permitted 6 to 9 months post-ACLR by 60% of therapists if satisfied with patient progress and capacity. Factors considered before RTS included knee strength (72.9%), functional capacity (86.4%), lower limb and trunk mechanics (62.7%), and psychological readiness (42.2%). Knee strength was assessed by manual muscle testing (39%), handheld dynamometry (15.3%), and isokinetic dynamometer (13.6%). While 60% of the therapists used single-limbed hop for distance for evaluating functional capacity, only 27.1% used a hop test battery. CONCLUSIONS: The surveyed physical therapists in Saudi Arabia demonstrated variations in the current rehabilitation practices and RTS criteria post-ACLR. Over half of the surveyed therapists considered preoperative rehabilitation essential to postoperative outcomes. However, the therapists should update their perspective with current evidence-based practice regarding the RTS timeframe, psychological readiness assessment for RTS, and knee strength evaluation using objective measurements.

Self-Reported Moderate-to-Vigorous Physical Activity: Its Association with Health-Related Quality of Life in a Large Cohort of People with Chronic Diseases.

The aim of this study was to investigate the dose-response relationship between physical activity and health-related quality of life (HRQoL) in a large population-based sample of people with chronic disease. We analysed the data of 29,271 adults (15,315 women) who were diagnosed with chronic diseases and participated in the Welsh Health Survey (Wales, UK; data collection 2011-2015). Participants were classified, based on their weekly minutes of moderate-to-vigorous physical activity (MVPA), into four groups as follows: inactive (no MVPA), insufficiently active (<150 min/week), sufficiently active (≥150-<300), and very active (≥300). The main outcome was HRQoL measured via the Short-Form 36 Health Survey (SF-36). This study found a curvilinear association between MVPA and HRQoL and a dose-response relationship for the perception of general health and vitality domains. Compared to inactive participants, those who were very active had higher HRQoL scores (coefficient = 12.54; 95% confidence interval [CI] 11.39-13.70), followed by sufficiently active (coefficient = 11.70; 95% CI 10.91-12.49) and insufficiently active (coefficient = 9.83; 95% CI 9.15-10.51) participants. The fully adjusted regression model showed curvilinear associations between MVPA and the domains of SF-36. Future research should find ways to motivate people with chronic diseases to engage in physical activity. The evidence to support regular exercise in individuals with chronic diseases in all age groups is strong and compelling, and patients should be encouraged to regularly devote more time to physical activity in order to improve their health and well-being.

Discovery of YSR734: A Covalent HDAC Inhibitor with Cellular Activity in Acute Myeloid Leukemia and Duchenne Muscular Dystrophy.

Histone deacetylases (HDACs) have emerged as powerful epigenetic modifiers of histone/non-histone proteins via catalyzing the deacetylation of ε-N-acetyl lysines. The dysregulated activity of these Zn2+-dependent hydrolases has been broadly implicated in disease, notably cancer. Clinically, the recurring dose-limiting toxicities of first-generation HDACi sparked a paradigm shift toward safer isoform-specific molecules. With pervasive roles in aggressive diseases, there remains a need for novel approaches to target these enzymes. Herein, we report the discovery of YSR734, a first-in-class covalent HDACi, with a 2-aminobenzanilide Zn2+ chelate and a pentafluorobenzenesulfonamide electrophile. This class I selective proof of concept modified HDAC2Cys274 (catalytic domain), with nM potency against HDAC1-3, sub-µM activity in MV4-11 cells, and limited cytotoxicity in MRC-9 fibroblasts. In C2C12 myoblasts, YSR734 activated muscle-specific biomarkers myogenin/Cav3, causing potent differentiation into myotubes (applications in Duchenne Muscular Dystrophy). Current efforts are focused on improving in vivo ADME toward a preclinical covalent HDACi.

Video-Based Simulation Among Saudi Undergraduate Nursing Students During COVID-19: A Qualitative Study.

Background Because of university closures due to COVID-19 confinement, video-based simulation, a training technique based on high-fidelity simulations, was introduced in reaction to the need to adapt high-fidelity clinical simulation experiences to digital platforms. Purpose This study aims to evaluate the perceptions of nursing students in Saudi Arabia regarding the shift from face-to-face simulation experiences to video-based simulation during the COVID-19 pandemic. Methods This study employed a phenomenological exploratory qualitative research design among 32 nursing students from various academic levels. Results The thematic analysis gave rise to five themes namely, "Enhanced Learning and satisfaction", "Improved communication skills", "Lack of hands-on experience", "More comfortable experience", and "Technical Barriers". Conclusion The students in this study have indicated that they were satisfied with video-based simulation, where they reported enhanced learning, better communication skills, and more perceived comfort, while concerns regarding technical issues and nursing skills were raised.

Inflammation-based scores in benign adrenocortical tumours are linked to the degree of cortisol excess: a retrospective single-centre study.

OBJECTIVE: Benign adrenocortical tumours are diagnosed in ∼5% of adults and are associated with cortisol excess in 30%-50% of cases. Adrenal Cushing's syndrome (CS) is rare and leads to multiple haematological alterations. However, little is known about the effects of the much more frequent mild autonomous cortisol secretion (MACS) on immune function. The aim of this study was to evaluate the haematological alterations in benign adrenocortical tumours with different degrees of cortisol excess. DESIGN AND METHODS: We investigated 375 patients: 215 with non-functioning adrenal tumours (NFAT), 138 with MACS, and 22 with CS. We evaluated the relationship between the degree of cortisol excess and full blood count as well as multiple inflammation-based scores, including the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune-inflammation index (SII). RESULTS: We observed a gradual and significant increase of leucocytes, neutrophils, and monocytes across the spectrum of cortisol excess, from NFAT over MACS to CS. Neutrophil-to-lymphocyte ratio and SII were significantly higher in both MACS and CS when compared to NFAT (P < .001 and P = .002 for NLR and P = .006 and P = .021 for SII, respectively). Conversely, LMR was lower in MACS and CS than in NFAT (P = .01 and <.001, respectively) but also significantly lower in CS compared to MACS (P = .007). CONCLUSIONS: Neutrophil-to-lymphocyte ratio, SII, and LMR correlated with the degree of cortisol excess in benign adrenocortical tumours and were altered in patients with CS and MACS. These findings suggest that, similar to clinically overt CS, MACS also affects the immune function, potentially contributing to the MACS-associated comorbidities.