Calcineurin is an adaptor required for assembly of the TCR signaling complex.

The serine/threonine phosphatase calcineurin is a component of the T cell receptor (TCR) signalosome, where it promotes T cell activation by dephosphorylating LckS59. Using small interfering RNA (siRNA)-mediated knockdown and CRISPR-Cas9-targeted genetic disruption of the calcineurin A chain α and ß isoforms, we find that calcineurin also functions as an adaptor in TCR-signaled human T cells. Unlike inhibition of its phosphatase activity, in the absence of calcineurin A, TCR signaling results in attenuated actin rearrangement, markedly reduced TCR-Lck microcluster formation and recruitment of the adaptor RhoH, and diminished phosphorylation of critical targets downstream of Lck such as TCRζ and ZAP-70. Reconstitution of deficient T cells with either calcineurin Aα or Aß restores TCR microcluster formation and signaling, as does reconstitution with a phosphatase-inactive Aα chain. These results assign a non-enzymatic adaptor function to calcineurin in the formation and stabilization of a functional TCR signaling complex.

Caregiver-assisted testing with HIV self-test kits for children 18 months and older: A GRADE systematic review.

Caregiver-assisted testing using HIV self-test (CG-HIVST) kits has been proposed to enhance paediatric HIV case finding and contribute toward ending paediatric HIV/AIDS by 2030. We conducted a systematic review to assess the risks and benefits of CG-HIVST. We searched nine electronic databases and consulted experts to identify relevant articles through 5 February, 2022. Studies comparing CG-HIVST to other testing services among children over 18-months, or to no intervention, were included. Outcomes included uptake, acceptability, diagnostic accuracy, feasibility, HIV positivity, linkage to care, social harm, values and preferences, costs, and cost-effectiveness. Risk of bias was assessed using relevant Cochrane tools and certainty of evidence was evaluated with GRADE. Among 2203 screened articles, nine observational studies from sub-Saharan Africa were included. All studies used and assessed caregiver-assisted testing using oral fluid-based HIVST. In one non-randomized intervention study of 6062 children, overall CG-HIVST uptake was lower than other standard testing services (3.30% vs. 56.71%). In the same study, HIV positivity following CG-HIVST appeared lower or comparable to standard testing (RR = 0.44; 95% CI: 0.06, 3.20). Two single-arm studies reported high linkage to confirmatory testing (97.48%) and treatment initiation (97.7%) among children reported positive with CG-HIVST. Pooled positive predictive value was 36.72% across three non-randomized intervention studies. Reported social harms were rare, and acceptability appeared high among caregivers taking up the intervention, but feasibility was unclear as some reported anxiety in relation to reactive results. Evidence was appraised very low certainty. Average CG-HIVST costs varied widely and were consistently higher than standard testing services. CG-HIVST may be acceptable, but feasibility remains uncertain with potential higher costs. Current evidence favours standard testing for uptake and positivity. Low positive predictive values raise concerns about false positives and potential harm. Programmes should prioritize evidence-based approaches for paediatric case-finding, while research to fully evaluate this approach continues.

A typology of HIV self-testing support systems: a scoping review.

To maximise the benefits of HIV self-testing (HIVST), it is critical to support self-testers in the testing process and ensure that they access appropriate prevention and care. To summarise systems and tools supporting HIVST (hereafter, 'support systems') and categorise them for future analysis, we synthesised the global data on HIVST support systems and proposed a typology. We searched five databases for articles reporting on one or more HIVST support systems and included 314 publications from 224 studies. Across 189 studies, there were 539 reports of systems supporting HIVST use; while across 115 studies, there were 171 reports of systems supporting result interpretation. Most commonly, these were pictorial instructions, followed by in-person demonstrations and in-person assistance while self-testing or reading self-test results. Less commonly, virtual interventions were also identified, including online video conferencing and smartphone apps. Smartphone-based automated result readers have been used in the USA, China, and South Africa. Across 173 studies, there were 987 reports of systems supporting post-test linkage to care; most commonly, these were in-person referrals/counselling, written referrals, and phone helplines. In the USA, Bluetooth beacons have been trialled to monitor self-test use and facilitate follow-up. We found that, globally, HIVST support systems use a range of methods, including static media, virtual tools, and in-person engagement. In-person and printed approaches were more common than virtual tools. Other considerations, such as linguistic and cultural appropriateness, may also be important in the development of effective HIVST programs.

Compulsive digital use: the risk and link of loneliness among adolescents.

PURPOSE OF REVIEW: The current rise of digital technologies is causing adolescents to spend more time on their digital devices, especially since the lockdown period of the pandemic. Adolescents are among those who are affected by lifestyle changes and are at risk of digital addiction due to the overuse of digital technologies. This opinion paper discusses the possible risk of loneliness among adolescents due to the overuse of digital devices. In this article, we would like to propose the concept of digital abuse and its risk of loneliness, as well as discuss some proposed solutions by referring to recent statistics and research evidence to reduce digital abuse among adolescents. RECENT FINDINGS: Evidence from previous studies highlights the association between digital addiction and loneliness among adolescents. Overusing digital devices among adolescents is also associated with various physical and psychological side effects. SUMMARY: Recent findings support the rapid rise of digital device usage among adolescents and its contributions to digital use. More research is needed to support existing interventions, provide early screening, and combat digital addiction to protect adolescents from the risks of loneliness due to the overuse of digital devices.

A Case of Anti-Leucine-Rich Glioma-Inactivated Protein 1 (Anti-LGI1) Limbic Encephalitis With Normal Imaging.

Anti-leucine-rich glioma-inactivated 1 limbic encephalitis (anti-LGI1 LE) is a rare autoimmune limbic encephalitis with a potentially misleading presentation that can delay diagnosis and treatment. The incremental progression of widely variable symptoms with a prominent behavioral disturbance can conceal the disease and prompt an initial psychiatric diagnosis. Although specific MRI findings ought to be evident by the time the disease progresses to frank limbic encephalitis, it appears inconsistent and ill-defined and is thus unreliable. Nevertheless, brain imaging remains prominent in the discussion, even included in some guidelines for diagnosing anti-LGI1 LE. Here, we present a case of a patient who presented after a suicide attempt with a long history of psychiatric issues, aberrant "spasms," and subsequently encephalopathy, who was eventually diagnosed with anti-LGI1 LE only after delayed CSF antibodies studies. In this patient, symptoms emerged over two years, with multiple brain MRIs being negative, including the one completed during the hospital admission in focus. The purpose of this case report is to encourage maintaining a broad differential when patients present with bizarre symptoms. This report underlies the importance of thorough clinical evaluation, utilization of multiple diagnostic resources, and the need for heightened awareness among healthcare providers about the subtleties of autoimmune encephalitis presentations. With anti-LGI1 LE already being severely underdiagnosed, it is important to continue reviewing various cases of patients who are diagnosed with anti-LGI1 LE and further review to understand its pathophysiology and common clinical presentation. This case also underscores the ongoing evolution in understanding anti-LGI1 LE and highlights that patients may present with unfamiliar symptoms or diagnostic challenges. The overall objective is to help providers recognize anti-LGI1 LE earlier, so treatment can be initiated sooner, leading to a better prognosis for patients.

Outcomes of Upper Gastrointestinal Bleeding in Hospitalized COVID-19 Patients in the United States: A Propensity-score Matched Analysis of a Large National Database.

Patients with cirrhosis that are hospitalized with COVID-19 infection have been found to have worse outcomes. No comparative study has been conducted between gastrointestinal (GI) bleeding in patients with cirrhosis who are diagnosed with COVID-19. We utilized the National Inpatient Sample (NIS) database to perform a retrospective analysis of 24, 050 patients diagnosed with cirrhosis and COVID-19. The identified patients were separated into variceal bleeding, nonvariceal bleeding, and no (or neither) GI bleeding groups. After performing propensity sample matching and multivariate analysis of mortality, we found no significant differences in mortality among the three groups. However, the variceal bleed group had a shorter length of stay (5.67 days lower than the no-bleed group). Esophagogastroduodenoscopy (EGD) with intervention was associated with reduced mortality in the variceal and nonvariceal bleeding groups. Acute kidney injury was a strong predictor of mortality in both bleeding groups. A native American race was found to be associated with higher mortality in the nonvariceal bleeding group. Our study suggests that there are various pathophysiological processes among the three groups, with no significant mortality differences with cirrhosis complications of GI bleeding.

Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample.

Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth's death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.

Prognostic value of left atrial size and function by cardiac magnetic resonance in non-ischemic cardiomyopathy.

To evaluate left atrial (LA) function and strain parameters by cardiac magnetic resonance imaging (CMR) in patients with non-ischemic cardiomyopathy (NICM) and evaluate the association of these parameters with long-term clinical outcomes. We retrospectively included 92 patients with NICM and 50 subjects with no significant cardiovascular disease (control group). We calculated LA volumes using the Simpson area-length method to derive LA ejection fraction and expansion index. LA reservoir (ƐR), conduit (ƐCD), and contractile strain (ƐCT) were measured using dedicated CMR software (cvi42, Circle Cardiovascular Imaging Inc., version 5.14). An adjusted multivariate regression analysis was performed to determine the association of LA parameters with death and heart failure hospitalization (HFH). NICM patients were older with male preponderance. The mean age for NICM patients was 59.6 ± 15.9 years, 64% males, and 73% whites versus 52.2 ± 12.4 years, 34% male and 64% white for controls. LA strain patterns were significantly lower in NICM patients when compared to controls. During a median follow-up of 58.9 months, 12 patients (13%) died and 33(35.9%) had a HFH. None of the clinical or CMR factors were significantly associated with death. On multivariate analysis, after adjusting for age and significant univariate variables, ƐR was the only variable significantly associated with the HFH (OR 0.98, CI 0.96-1.0). Unadjusted and adjusted Cox proportional hazard models divided by the median ƐR (~ 18%) showed a significant difference in HFH over time (χ2 statistic = 21.1; P value = 0.03). In NICM patients, all LA strain components were reduced. ƐR was found to be significantly associated with HFH.

Targeted therapies in advanced biliary malignancies: a clinical review.

INTRODUCTION: Despite several therapeutic advancements, the proportion of patients with advanced biliary tract cancers (BTC) surviving 5 years from diagnosis remains dismal. The increasing recognition of targetable genetic alterations in BTCs has ushered in a new era in the treatment of these patients. Newer therapeutic agents targeting mutations such as isocitrate dehydrogenase (IDH), fibroblastic growth factor receptor (FGFR), human epidermal growth factor receptor (HER), and so on have established a new standard of care for treatment upon progression on frontline therapy in patients with disease harboring these mutations. AREAS COVERED: The current review aims to concisely summarize progress with various targeted therapy options for BTC. We also briefly discuss future directions in clinical and translational research for the adoption of a personalized approach for the treatment of unresectable or advanced BTC. EXPERT OPINION: Several new agents continue to emerge as feasible treatment options for patients with advanced BTC harboring targetable mutations. There is a growing need to identify mechanisms to conquer primary and acquired resistance to these agents. The identification of potential biomarkers that predict response to targeted therapy may be helpful in adopting a more tailored approach. All patients receiving treatment for advanced BTC should undergo tissue genomic profiling at diagnosis.

Assessment of Direct Medical Cost of Hospitalized COVID-19 Adult Patients in Kuwait During the First Wave of the Pandemic.

Objective: This study aims to estimate the direct medical cost of COVID-19 hospitalizations and to utilize prevalence estimates from Jaber Al-Ahmad Hospital to estimate the direct medical cost of all hospitalized adult patients in Kuwait using a decision tree analysis. Methods: A cost-of-illness model was developed. The Ministry of Health perspective was considered, direct medical costs were estimated from July 1st to September 30th, using a bottom-up approach. The mean cost per hospitalized patient was estimated using a decision analysis model. Prevalence estimates of ambulance use, use of ER, ICU admission, and mortality were considered in the current study. Patients aged 18 years and above with a confirmed diagnosis of COVID-19 were included. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed. Results: Data for 2986 patients were analyzed. The mean age was 61 (SD= 11) years old. Most of the patients were Kuwaiti (2864, 95.91%), and more than half were females (1677, 56.16%). Of the total hospital admissions, 417 patients (14%) were admitted to the ICU. The average length of the hospital stay was 11 (SD= 9) days, and among all hospital admissions, 270 (9.04%) patients died. The total estimated direct medical cost of hospitalized patients at Jaber Al-Ahmad Hospital was $47,213,768 (14,283,203.6 KD). The average cost of hospital stay per patient was estimated at $15,498 (4,688.60 KD). The weighted average cost per hospitalized patient in Kuwait was estimated at $16,373 (4,953.08 KD). The total direct medical cost of hospitalized COVID-19 patients in Kuwait during the study period was estimated at $174,372,450 (52,751,502 KD). Conclusion: The COVID-19 pandemic constituted a significant burden on the Kuwaiti healthcare system. The findings of this study urge the need for preventive care strategies to reduce adverse health outcomes and the economic impact of the pandemic.

The Role of Point-of-Care Ultrasound in the Emergency Department in the Diagnosis and Management of Infective Endocarditis.

Infective endocarditis (IE) is a serious cardiovascular condition with the potential to lead to severe valvular regurgitation. We present a case of a 65-year-old male who presented with a fever and was diagnosed with IE through point-of-care ultrasound (POCUS). The patient's condition subsequently led to severe aortic regurgitation. Timely diagnosis facilitated by POCUS played a crucial role in the management of this case. The patient underwent successful timely surgical intervention to prevent further infective embolism and heart failure due to severe acute aortic regurgitation. This case underscores the pivotal role of POCUS in the early diagnosis and multidisciplinary management of cardiology diseases, highlighting its importance in delivering optimal patient care.

ARISCAT and LAS VEGAS risk scores for predicting postoperative pulmonary complications after cardiac surgery: a cohort study.

Background: Postoperative pulmonary complications (PPCs) could lead to morbidity, mortality, and prolonged hospital stay. Different risk-scoring systems are used to predict the identification of patients at risk of developing PPCs. The diagnostic accuracies of the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) and Local Assessment of Ventilatory Management During General Anaesthesia for Surgery (LAS VEGAS) risk scores are compared in prediction of PPCs taking pulmonary complication as the gold standard in cardiac surgery. Materials and methods: A prospective cohort study with consecutive sampling technique. A total of 181 patients were included. Quantitative data is presented as simple descriptive statistics giving mean and standard deviation, and qualitative variables are presented as frequency and percentages. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracies are also calculated. Results: Total 181 post-cardiac surgery patients were analyzed. The median [interquartile range] of age, height, weight, and BMI were 60.0 [52.0-67.0] years, 163.0 [156.0-168.0] cm, 71.0 [65.0-80.0] kg and 27.3 [24.2-30.4] kg/m2. 127 (70.2%) were male, and 54 (29.8%) were female. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ARISCAT for the prediction of PPCs were (94.9%, 4.65%, 76.1%, 22.9% and 73.4%), whereas LAS VEGAS were (97.1%, 4.65%, 76.5%, 33.3% and 75.1%), respectively. Conclusion: Both the ARISCAT and LAS VEGAS risk scores are of limited value in cardiac surgery patients for the prediction of postoperative pulmonary complications, based on the predicted scores in this study.

Adolescents With a High Burden of New-Onset Mood Symptoms After Sport-Related Concussion Benefit From Prescribed Aerobic Exercise, a Secondary Analysis of 2 Randomized Controlled Trials.

OBJECTIVE: Approximately 20% of students with sport-related concussion (SRC) report new symptoms of anxiety and depression which may be associated with delayed recovery and increased risk for developing a mood disorder. Early prescribed aerobic exercise facilitates recovery in athletes with concussion-related exercise intolerance. We studied the effect of aerobic exercise treatment on new mood symptoms early after SRC. DESIGN: Exploratory secondary analysis of 2 randomized controlled trials (RCT). SETTING: Sports medicine clinics associated with UB (Buffalo, NY), CHOP (Philadelphia, PA), and Boston Children's Hospital (Boston, MA). PARTICIPANTS: Male and female adolescents (aged 13-18 years) diagnosed with SRC (2-10 days since injury). INTERVENTIONS: Participants were randomized to individualized targeted heart rate aerobic exercise (n = 102) or to a placebo intervention designed to mimic relative rest (n = 96). MAIN OUTCOME MEASURES: Incidence of Persisting Post-Concussive Symptoms (PPCS, symptoms ≥28 days). RESULTS: First RCT recruited from 2016 to 2018 and the second from 2018 to 2020. Of 198 adolescents, 156 (79%) reported a low burden (mean 1.2 ± 1.65/24) while 42 (21%) reported a high burden (mean 9.74 ± 3.70/24) of emotional symptoms before randomization. Intervention hazard ratio for developing PPCS for low burden was 0.767 (95% CI, 0.546-1.079; P = 0.128; ß = 0.085) and for high burden was 0.290 (95% CI, 0.123-0.683; P = 0.005; ß = 0.732). CONCLUSIONS: High burden of mood symptoms early after injury increases risk for PPCS, but the sports medicine model of providing early targeted aerobic exercise treatment reduces it. Nonsports medicine clinicians who treat patients with a high burden of new mood symptoms after concussion should consider prescribing aerobic exercise treatment to reduce the risk of PPCS and a mood disorder.

Outcomes of biological therapy in patients with severe asthma with chronic rhinosinusitis in Saudi Arabia: patients with nasal polyps versus those without nasal polyps.

BACKGROUND: This study's purposes were to evaluate the impact of biological therapies on outcomes in patients with severe asthma (SA) and chronic rhinosinusitis (CRS) and to compare these effects among those with NP (CRSwNP) versus those without NP (CRSsNP) in the "real-world" setting in Saudi Arabian patients. METHODS: From March to September 2022, a retrospective observational cohort study was undertaken at the severe asthma clinics of the Armed Forces Hospital-Southern Region (AFHSR) and King Khalid University Hospital, Abha, Saudi Arabia, to delineate the effects of dupilumab therapy. Outcomes were assessed, including clinical outcomes, FEV1, and laboratory findings before and one year after dupilumab. Post-therapy effects were compared between CRSwNP and CRSsNP. RESULTS: Fifty subjects were enrolled, with a mean age of 46.56. There were 27 (54%) females and 23(46%) males. Significant improvements in clinical parameters (frequency of asthma exacerbations and hospitalizations, the use of OCs, anosmia, SNOTT-22, and the ACT), FEV1, and laboratory ones (serum IgE and eosinophilic count) were observed 6 and 12 months after using dupilumab (p < 0.001), respectively. However, after 12 months of dupilumab therapy, there were no significant differences between those with and without NP with regards to clinical (anosmia, ACT, and OCs use), laboratory (eosinophilic count, serum IgE level) parameters, and FEV1%. CONCLUSIONS: Patients with CRS experienced significant improvements in clinical, FEV1, and laboratory outcomes after dupilumab therapy. However, these improvements were not maintained when comparing CRSwNP with CRSsNP. There were no significant differences between those with and without NP regarding ACT and OCs use or laboratory (eosinophilic count, serum IgE level) parameters. Further prospective multicenter studies are warranted.

Predictive Value of Clinical, CSF and Vessel Wall MRI Variables in Diagnosing Primary Angiitis of the CNS.

Background and Objectives: Without brain biopsy, there are limited diagnostic predictors to differentiate primary angiitis of the CNS (PACNS) from intracranial atherosclerotic disease (ICAD). We examined the utility of clinical, CSF, and quantitative vessel wall magnetic resonance imaging (VWMRI) variables in predicting PACNS from ICAD. Methods: In this cross-sectional design, observational study, we reviewed electronic medical records to identify patients (18 years and older) who presented to our medical center between January 2015 and December 2021 for ischemic stroke due to intracranial vasculopathy. Patients with biopsy-proven PACNS, probable PACNS, or ICAD were included. Patients with secondary CNS vasculitis or no VWMRI data were excluded. On VWMRI, for each patient, a total of 20 vessel wall segments were analyzed for percent concentricity, percent irregularity, and concentricity to eccentricity (C/E) ratios. We also collected several clinical and CSF variables. Using logistic regression models, we assessed the diagnostic value of VWMRI, CSF, and clinical variables in predicting PACNS in patients with biopsy-proven disease. We then performed a sensitivity analysis to assess predictors of biopsy-proven and probable PACNS. Results: Thirty-two patients with ICAD (54.2%) and 27 patients with PACNS (45.8%) were included. Of the patients with PACNS, 21 (77.8%) were not biopsied and considered probable PACNS. Twenty-four patients with ICAD (75%) and 6 biopsy-proven patients with PACNS (22.2%) showed large vessel involvement and were included in the primary analysis. Encephalopathy (odds ratio [OR], 7.60; 95% CI 1.07-54.09) and seizure (OR 23.00; 95% CI 1.77-298.45) were significantly associated with PACNS. All patients were included in the sensitivity analysis, in which headache significantly predicted PACNS (OR 7.60; 95% CI 1.07-54.09). In the primary analysis, for every 1 white blood cell/µL increase in CSF, there was a 47% higher odds of PACNS (OR 1.47; 95% CI 1.04-2.07). On VWMRI, a C/E ratio >1 (OR 115.00; 95% CI 6.11-2165.95), percent concentricity ≥50% (OR 55.00; 95% CI 4.13-732.71), and percent irregularity <50% (OR 55.00; 95% CI 4.13-732.71) indicated significantly higher odds of PACNS compared with ICAD. Discussion: Our results suggest that quantitative VWMRI metrics, CSF pleocytosis, and clinical features of encephalopathy, seizure, and headache significantly predict a diagnosis of probable PACNS when compared with ICAD.

Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.

Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.

The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients.

PURPOSE: To investigate the allelic and genotypic frequencies of the two genetic variations, NC_000006.12: g.160275887C > T (rs662301) and NC_000006.12:g.160231826 T > C (rs315978), in the SLC22A2 gene among the Saudi population. The primary goal is to elucidate potential associations with these genetic variations and the response to metformin therapy over 6 months to enhance our knowledge of the genetic basis of Type 2 Diabetes Mellitus (T2DM) and its clinical management in the Saudi population. MATERIALS/METHODS: 76 newly diagnosed T2DM patients, aged 30 to 60, of both sexes and Saudi origin, were treated with metformin monotherapy. Blood samples were collected before and after 6 months of therapy,80 healthy individuals were included as controls. Genomic DNA was extracted. Genotyping of the SLC22A2 genetic variations was performed using TaqMan® SNP Genotyping Assays. Binary logistic regression was utilized to evaluate how certain clinical parameters influence T2DM concerning the presence of SLC22A2 gene variants. RESULTS: Among these patients, 73.3 % were responders, and 26.7 % were non-responders. For these variants, no statistically significant differences in genotype or allele frequencies were observed between responders and non-responders (p = 0.375 and p = 0.384 for rs662301; p = 0.473 and p = 0.481 for rs315978, respectively). For the SLC22A2 variant rs662301, the C/C genotype was significantly associated with increased T2DM risk with age and elevated HbA1c levels. Similarly, rs315978 revealed higher T2DM susceptibility and HbA1c elevation in C/C genotype carriers, specifically with advancing age compared to individuals with C/T and T/T genotypes. CONCLUSION: The study offers insights into the genetic landscape of T2DM in Saudi Arabia. Despite the absence of significant associations with treatment response, the study suggests potential age-specific associations, this highlights the complexity of the disease. This research underscores the necessity for expanded research, considering diverse populations and genetic factors, to develop personalized treatment approaches. This study serves as a foundation for future investigations into the Saudi population, recognizing the need for a larger sample size.

Electrochemical detection of nalbuphine drug using oval-like ZnO nanostructure-based sensor.

Monitoring pharmaceutical drugs in various mediums is crucial to mitigate adverse effects. This study presents a chemical sensor using an oval-like zinc oxide (ZnO) nanostructure for electrochemical detection of nalbuphine. The ZnO nanostructure, produced via an efficient sol-gel technique, was extensively characterized using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-visible spectrophotometry, and fourier transform infrared spectroscopy (FTIR). A slurry of the ZnO nanostructure in a binder was applied to a glassy carbon electrode (GCE). The sensor's responsiveness to nalbuphine was assessed using linear sweep voltammetry (LSV), achieving optimal performance by fine-tuning the pH. The sensor demonstrated a proportional response to nalbuphine concentrations up to 150.0 nM with a good regression coefficient (R2) and a detection limit of 6.20 nM (S/N ratio of 3). Selectivity was validated against various interfering substances, and efficacy was confirmed through real sample analysis, highlighting the sensor's successful application for nalbuphine detection.