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Intussusception is a common surgical emergency in children. Clinical suspicion and radiological evaluation confirm the diagnosis of the disease. Enema reduction is the first line of management. This study aimed to explore the risk factors associated with enema reduction failure. A retrospective analysis of patients diagnosed with intussusception at three different hospitals in different countries from January 2016 to December 2022. Data collected included demographics, presenting symptoms, duration of symptoms, management, outcomes, and follow-ups. A total of 290 cases of intussusception were included in the study. Ages ranged from 1 to 36 months, with a median age of 15 months. All children underwent an enema reduction which was successful in 92.4%. Failure of reduction was seen in 16.7% of females compared to 6.4% of males, and it was significantly seen in children below the age of 1 year compared to older children. Failure of reduction significantly increases with the duration of symptoms and in children who present with bilious vomiting and currant jelly stool. In conclusion, Failure of enema reduction was more prevalent in females, in children below the age of 1 year and who present late, as well as children who had bilious vomiting and currant jelly stool. This study identified several risk factors associated with failed enema reduction in children with intussusception. Recognizing the risk factors can help guide clinicians in the management and anticipation of outcomes., (© 2024. The Author(s).)

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = - 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28-30, 2024, in Estoril, Lisbon, Portugal., (© 2024. The Author(s).)

Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus. Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent-angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer., (© 2024. The Author(s).)

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels., (© 2024. The Author(s).)

Asthma is a prevalent respiratory condition that poses a substantial burden on public health in the United States. Understanding its prevalence and associated risk factors is vital for informed policymaking and public health interventions. This study aims to examine asthma prevalence and identify major risk factors in the U.S., Population: Our study utilized NHANES data between 1999 and 2020 to investigate asthma prevalence and associated risk factors within the U.S., Population: We analyzed a dataset of 64,222 participants, excluding those under 20 years old. We performed binary regression analysis to examine the relationship of demographic and health related covariates with the prevalence of asthma. The study found that asthma affected 8.7% of the U.S., Population: Gender emerged as a significant factor, with 36.0% of asthma patients being male and 64.0% female (p < 0.001). Individuals aged 60 and older having the highest asthma prevalence at 34.0%. Non-Hispanic whites had the highest prevalence at 46.4%, followed by non-hispanic blacks at 26.0%. In contrast, Mexican Americans and other hispanic individuals had lower rates, at 9.6% and 9.0%, respectively. Females were 1.76 times more likely to have asthma than males (p < 0.001). Obese individuals had a 1.74 times higher likelihood of current asthma compared to underweight individuals (p < 0.001). Notably, both Non-Hispanic Whites and Non-Hispanic Blacks showed higher odds of current asthma compared to Mexican Americans (with adjusted odds ratios of 2.084 and 2.096, respectively, p < 0.001). The research findings indicate that asthma is prevalent in 8.7% of the U.S., Population: Our study highlights that individuals who are female, have low income, are obese, and smoke have the highest likelihood of being affected by asthma. Therefore, public health policies should prioritize addressing these risk factors in their preventive strategies., (© 2024. The Author(s).)

Hearing loss is the most predominant sensory defect occurring in pediatrics, of which, 66% cases are attributed to genetic factors. The prevalence of hereditary hearing loss increases in consanguineous populations, and the prevalence of hearing loss in Qatar is 5.2%. We aimed to investigate the genetic basis of nonsyndromic hearing loss (NSHL) in Qatar and to evaluate the diagnostic yield of different genetic tests available. A retrospective chart review was conducted for 59 pediatric patients with NSHL referred to the Department of Adult and Pediatric Medical Genetics at Hamad Medical Corporation in Qatar, and who underwent at least one genetic test. Out of the 59 patients, 39 were solved cases due to 19 variants in 11 genes and two copy number variants that explained the NSHL phenotype. Of them 2 cases were initially uncertain and were reclassified using familial segregation. Around 36.8% of the single variants were in GJB2 gene and c.35delG was the most common recurrent variant seen in solved cases. We detected the c.283C > T variant in FGF3 that was seen in a Qatari patient and found to be associated with NSHL for the first time. The overall diagnostic yield was 30.7%, and the diagnostic yield was significantly associated with genetic testing using GJB2 sequencing and using the hearing loss (HL) gene panel. The diagnostic yield for targeted familial testing was 60% (n = 3 patients) and for gene panel was 50% (n = 5). Thus, we recommend using GJB2 gene sequencing as a first-tier genetic test and HL gene panel as a second-tier genetic test for NSHL. Our work provided new insights into the genetic pool of NSHL among Arabs and highlights its unique diversity, this is believed to help further in the diagnostic and management options for NSHL Arab patients., (© 2024. The Author(s).)

Low HDL levels are associated with an increased stroke incidence and worsened long-term outcomes. The aim of this study was to assess the relationship between HDL levels and long-term stroke outcomes in the Arab population. Patients admitted to the Qatar Stroke Database between 2014 and 2022 were included in the study and stratified into sex-specific HDL quartiles. Long-term outcomes included 90-Day modified Rankin Score (mRS), stroke recurrence, and post-stroke cardiovascular complications within 1 year of discharge. Multivariate binary logistic regression analyses were performed to identify the independent effect of HDL levels on short- and long-term outcomes. On multivariate binary logistic regression analyses, 1-year stroke recurrence was 2.24 times higher (p = 0.034) and MACE was 1.99 times higher (p = 0.009) in the low-HDL compared to the high-HDL group. Mortality at 1 year was 2.27-fold in the low-normal HDL group compared to the reference group (p = 0.049). Lower sex-specific HDL levels were independently associated with higher adjusted odds of 1-year post-stroke mortality, stroke recurrence, and MACE (p < 0.05). In patients who suffer a stroke, low HDL levels are associated with a higher risk of subsequent vascular complication., (© 2024. The Author(s).)

Diabetes mellitus (DM) is a prevalent chronic metabolic disorder linked to increased morbidity and mortality. With a significant portion of cases remaining undiagnosed, particularly in the Middle East North Africa (MENA) region, more accurate and accessible diagnostic methods are essential. Current diagnostic tests like fasting plasma glucose (FPG), oral glucose tolerance tests (OGTT), random plasma glucose (RPG), and hemoglobin A1c (HbA1c) have limitations, leading to misclassifications and discomfort for patients. The aim of this study is to enhance diabetes diagnosis accuracy by developing an improved predictive model using retinal images from the Qatari population, addressing the limitations of current diagnostic methods. This study explores an alternative approach involving retinal images, building upon the DiaNet model, the first deep learning model for diabetes detection based solely on retinal images. The newly proposed DiaNet v2 model is developed using a large dataset from Qatar Biobank (QBB) and Hamad Medical Corporation (HMC) covering wide range of pathologies in the the retinal images. Utilizing the most extensive collection of retinal images from the 5545 participants (2540 diabetic patients and 3005 control), DiaNet v2 is developed for diabetes diagnosis. DiaNet v2 achieves an impressive accuracy of over 92%, 93% sensitivity, and 91% specificity in distinguishing diabetic patients from the control group. Given the high prevalence of diabetes and the limitations of existing diagnostic methods in clinical setup, this study proposes an innovative solution. By leveraging a comprehensive retinal image dataset and applying advanced deep learning techniques, DiaNet v2 demonstrates a remarkable accuracy in diabetes diagnosis. This approach has the potential to revolutionize diabetes detection, providing a more accessible, non-invasive and accurate method for early intervention and treatment planning, particularly in regions with high diabetes rates like MENA., (© 2024. The Author(s).)

There is variability in the metabolic health status among individuals presenting with obesity; some may be metabolically healthy, while others may have developed the metabolic syndrome, a cluster including insulin resistance, hypertension, dyslipidemia, and increased risk of cardiovascular disease and type 2 diabetes. The mechanisms contributing to this metabolic heterogeneity are not fully understood. To address this question, plasma samples from 48 individuals with BMI ≥ 35 kg/m 2 were examined (27 with and 21 without metabolic syndrome). Fasting plasma samples were subjected to Olink proteomics analysis for 184 cardiometabolic and inflammation-enriched proteins. Data analysis showed a clear differentiation between the two groups with distinct plasma protein expression profiles. Twenty-four proteins were differentially expressed (DEPs) between the two groups. Pathways related to immune cell migration, leukocyte chemotaxis, chemokine signaling, mucosal inflammatory response, tissue repair and remodeling were enriched in the group with metabolic syndrome. Functional analysis of DEPs revealed upregulation of 15 immunological pathways. The study identifies some of the pathways that are altered and reflect metabolic health in individuals with obesity. This provides valuable insights into some of the underlying mechanisms and can lead to identification of therapeutic targets to improve metabolic health in individuals with obesity., (© 2023. The Author(s).)

As the global vaccination mass campaign against COVID-19 extended to children aged 5 to 11 years, some parents remained hesitant about their children being administered the vaccine despite data supporting its safety. Parent vaccine hesitancy (PVH) may have predisposed certain groups of children, particularly those with autism spectrum disorder (ASD), to COVID-19 when other neurotypical children would have been vaccinated. We investigated the current PVH in 243 parents of children with ASD and 245 controls using the Parent Attitudes about Childhood Vaccines (PACV) scale. The study was conducted in Qatar from May to October 2022. Overall, 15.0% [95% CI 11.7%; 18.3%] of parents were vaccine-hesitant, with no difference (p = 0.054) between groups (ASD children [18.2%] vs. controls [11.7%]). The only sociodemographic factor associated with higher vaccine hesitancy was being a mother (as compared to being a father). The COVID-19 vaccine receipt rate at the time of the study did not differ between ASD (24.3%) and non-ASD groups (27.8%). Around two-thirds of parents of children with ASD refused or were unsure about vaccinating their children against COVID-19. We found that the intent to vaccinate against COVID-19 was higher in parents who were married and in those with a lower PACV total score. Continued public health efforts are needed to address vaccine hesitancy among parents., (© 2023. The Author(s).)

The awareness of cardiovascular diseases (CVDs) contributes to the complications and fatality rates from these diseases among individuals; however, no previous study in Syria was conducted on this topic; thus, this study aims to assess Syrians' awareness of CVDs warning symptoms and risk factors. This online cross-sectional study was performed in Syria between the 1st and 25th of August 2022. The inclusion criteria for the sample were citizens of Syria over 18 who currently reside in Syria. The questionnaire included open- and closed-ended questions to assess the awareness of CVDs. A total of 1201 participants enrolled in the study with a response rate of 97.2%; more than half of the participants (61.4%) were aged 18-24. The most recognizable risk factors and warning signs when asking close-ended and open-ended questions were smoking (95.2%, 37.1%) and chest pain (87.8%, 24.8%), respectively. Overall knowledge scores for risk factors and warning signs were (61.5%). Regarding knowledge score of CVDs risk factors and warning signs, participants aged 45-54 scored higher than other age groups, and respondents with a university education level had a higher score than other educational levels (15.7 ± 0.3), (14.5 ± 0.1), respectively. Participants aged 45-54 have a higher probability of good knowledge of CVDs risk factors and warning signs than participants aged 18-24 (OR = 4.8, P value < 0.001), while participants living in the countryside were less likely to have good knowledge of CVDs risk factors and warning signs than city residents (OR = 0.6, P value < 0.05). According to our results, there is inadequate knowledge of the risk factors and warning signs of CVDs. Consequently, there is a greater need to raise CVD awareness and learning initiatives on the disease's risk factors and symptoms., (© 2023. The Author(s).)

The goal of this study was to develop a predictive machine learning model to predict the risk of prolonged mechanical ventilation (PMV) in patients admitted to the intensive care unit (ICU), with a focus on laboratory and Arterial Blood Gas (ABG) data. This retrospective cohort study included ICU patients admitted to Rajaei Hospital in Shiraz between 2016 and March 20, 2022. All adult patients requiring mechanical ventilation and seeking ICU admission had their data analyzed. Six models were created in this study using five machine learning models (PMV more than 3, 5, 7, 10, 14, and 23 days). Patients' demographic characteristics, Apache II, laboratory information, ABG, and comorbidity were predictors. This study used Logistic regression (LR), artificial neural networks (ANN), support vector machines (SVM), random forest (RF), and C.5 decision tree (C.5 DT) to predict PMV. The study enrolled 1138 eligible patients, excluding brain-dead patients and those without mechanical ventilation or a tracheostomy. The model PMV > 14 days showed the best performance (Accuracy: 83.63-98.54). The essential ABG variables in our two optimal models (artificial neural network and decision tree) in the PMV > 14 models include FiO 2 , paCO 2 , and paO 2 . This study provides evidence that machine learning methods outperform traditional methods and offer a perspective for achieving a consensus definition of PMV. It also introduces ABG and laboratory information as the two most important variables for predicting PMV. Therefore, there is significant value in deploying such models in clinical practice and making them accessible to clinicians to support their decision-making., (© 2023. The Author(s).)

The co-existence of diabetic ketoacidosis (DKA) with acute pancreatitis (AP) is associated with unfavorable clinical outcomes. However, diagnosing AP in DKA patients is challenging and often missed due to overlapping symptoms. The aim of this retrospective observational study was to compare the clinical characteristics and outcomes of patients with concomitant DKA and AP or DKA alone. Data of patients with DKA admitted between January 2015 to August 2021 to four hospitals in Qatar was extracted from the electronic health record (Cerner). American Diabetes Association criteria and Atlanta criteria were used for DKA and AP diagnosis, respectively. Independent T-test or Mann-Whitney U test was used to analyze continuous variables, whereas categorical variables were analyzed via Chi-square or Fischer exact tests as appropriate. Univariate and multivariate logistic regression models were generated to assess the correlations. A p-value of < 0.05 was considered statistically significant. Of 936 patients with DKA, 84 (9.0%) had coexisting AP. AP was most common in the Asian race (66%, p < 0.001). Patients with DKA and AP were older, had higher admission anion-gap, white cell count, hemoglobin (hb), neutrophil/lymphocyte ratio, urea, creatinine, maximum blood glucose during the episode, total cholesterol and triglyceride level (TGL) (p < 0.05). They had a lower admission venous pH and bicarbonate at 6 h. Patients in the DKA with AP group also had a longer length of stay (LOS), DKA duration and a higher rate of ICU admission (p-values ≤ 0.001). In-hospital mortality, 3-month all-cause readmission, 6-month and 12-month DKA recurrence did not differ between the two groups. Univariate logistic regression analysis showed age, Asian ethnicity, male gender, T2D, admission WBC count, hb, urea, creatinine, potassium, venous pH, bicarbonate, anion gap, total cholesterol, TGL and LDL level were significantly associated with the development of DKA with AP (p < 0.05). In multivariate logistic regression analysis, age and total cholesterol level were associated with concomitant DKA and AP (p < 0.05). Patients with concomitant DKA and AP have more severe derangement in markers of DKA severity, inflammation, kidney injury and metabolic profile, along with a longer DKA duration, LOS and requirement for ICU support compared to DKA patients without AP. This highlights the clinical significance of diagnosing the co-existence of DKA with AP, as the combination results in significantly worse clinical outcomes and greater healthcare utilization than in patients with only DKA., (© 2023. The Author(s).)

Congenital anomalies (CAs) are a leading cause of morbidity and mortality in early life. We aimed to assess the incidence, risk factors, and outcomes of major CAs in the State of Qatar. A population-based retrospective data analysis of registry data retrieved from the Perinatal Neonatal Outcomes Research Study in the Arabian Gulf (PEARL-Peristat Study) between April 2017 and March 2018. The sample included 25,204 newborn records, which were audited between April 2017 and March 2018, of which 25,073 live births were identified and included in the study. Maternal risk factors and neonatal outcomes were assessed for association with specific CAs, including chromosomal/genetic, central nervous system (CNS), cardiovascular system (CVS), facial, renal, multiple congenital anomalies (MCAs) using univariate and multivariate analyses. The incidence of any CA among live births was 1.3% (n = 332). The most common CAs were CVS (n = 117; 35%), MCAs (n = 69, 21%), chromosomal/genetic (51; 15%), renal (n = 39; 12%), CNS (n = 20; 6%), facial (14, 4%), and other (GIT, Resp, Urogenital, Skeletal) (n = 22, 7%) anomalies. Multivariable regression analysis showed that multiple pregnancies, parity ≥ 1, maternal BMI, and demographic factors (mother's age and ethnicity, and infant's gender) were associated with various specific CAs. In-hospital mortality rate due to CAs was estimated to be 15.4%. CAs were significantly associated with high rates of caesarean deliveries (aOR 1.51; 95% CI 1.04-2.19), Apgar < 7 at 1 min (aOR 5.44; 95% CI 3.10-9.55), Apgar < 7 at 5 min (aOR 17.26; 95% CI 6.31-47.18), in-hospital mortality (aOR 76.16; 37.96-152.8), admission to neonatal intensive care unit (NICU) or perinatal death of neonate in labor room (LR)/operation theatre (OT) (aOR 34.03; 95% CI 20.51-56.46), prematurity (aOR 4.17; 95% CI 2.75-6.32), and low birth weight (aOR 5.88; 95% CI 3.92-8.82) before and after adjustment for the significant risk factors. This is the first study to assess the incidence, maternal risk factors, and neonatal outcomes associated with CAs in the state of Qatar. Therefore, a specialized congenital anomaly data registry is needed to identify risk factors and outcomes. In addition, counselling of mothers and their families may help to identify specific needs for pregnant women and their babies., (© 2023. The Author(s).)

Bone fractures are a global public health concern, yet no thorough investigation of low-dose aspirin usage to prevent fractures in the elderly has been conducted. Many interventional human and animal studies have tried to detect the correct role of low-dose aspirin on fractures in elderly persons. The literature doesn't consist of a retrospective observational study that includes a large number of older individuals and evaluates the accurate effect of aspirin on the fractures post falling from low heights. This cross-sectional includes 7132 elderly persons and aimed to detect if there was a link between taking low-dose aspirin to prevent fractures in the elderly. Data was extracted from the National Health and Nutrition Examination Survey (NHANES) database for 2017-2020 and 2013-2014. Demographic and examination data were collected during in-home interviews and study visits to a mobile examination center. Standardized questionnaires were used to collect information such as age, gender, race, educational level, and family income-to-poverty ratio. Body mass index (BMI), weight, standing height, upper leg length, upper arm length, arm circumference, and wrist circumference were all measured during the examination. The study examined 8127 patients, with 7132 elderly patients suitable for data analysis. The odds ratio of fractures due to a fall from standing height or less was 0.963 (95 percent confidence interval 0.08-1.149) in low-dose aspirin users, while having parents with osteoporosis had a related risk of 1.23. (95 percent confidence interval 0.81-1.8). The total number of fractures was 1295; with hip fractures constituting up to 13.82%, wrist fractures of 66.56%, and spine fractures of 19.61%. There was no significant difference in femur and spine bone mineral density (BMD) in the two groups (use low dose aspirin and don't use). Females had a 5.6 times greater fracture risk related to a fall from standing height or less (1 time or more) than males (P-value < 0.001). Furthermore, taking aspirin had no effect on the occurrence of fractures from standing height or less in older people (P-value = 0.468). In addition, the logistic regression after performing the propensity matching score confirmed that there was no impact of taking aspirin on the occurrence of fractures (P-value > 0.05). This cross-sectional study reveals that taking low-dose aspirin to prevent fractures in the elderly is statistically insignificant. However, fractures are more common in older persons, especially in older women; thus, more widespread injury prevention initiatives and access to osteoporosis prevention and diagnosis for older people should improve to minimize the overall burden., (© 2023. The Author(s).)

Cytokines are major players in orchestrating inflammation, disease pathogenesis and severity during COVID-19 disease. However, the role of IL-19 in COVID-19 pathogenesis remains elusive. Herein, through the analysis of transcriptomic datasets of SARS-CoV-2 infected lung cells, nasopharyngeal swabs, and lung autopsies of COVID-19 patients, we report that expression levels of IL-19 and its receptor, IL-20R2, were upregulated following SARS-CoV-2 infection. Of 202 adult COVID-19 patients, IL-19 protein level was significantly higher in blood and saliva of asymptomatic patients compared to healthy controls when adjusted for patients' demographics (P < 0.001). Interestingly, high saliva IL-19 level was also associated with COVID-19 severity (P < 0.0001), need for mechanical ventilation (P = 0.002), and/or death (P = 0.010) within 29 days of admission, after adjusting for patients' demographics, diabetes mellitus comorbidity, and COVID-19 serum markers of severity such as D-dimer, C-reactive protein, and ferritin. Moreover, patients who received interferon beta during their hospital stay had lower plasma IL-19 concentrations (24 pg mL -1 ) than those who received tocilizumab (39.2 pg mL -1 ) or corticosteroids (42.5 pg mL -1 ). Our findings indicate that high saliva IL-19 level was associated with COVID-19 infectivity and disease severity., (© 2022. The Author(s).)

Segmentation of abdominal Computed Tomography (CT) scan is essential for analyzing, diagnosing, and treating visceral organ diseases (e.g., hepatocellular carcinoma). This paper proposes a novel neural network (Res-PAC-UNet) that employs a fixed-width residual UNet backbone and Pyramid Atrous Convolutions, providing a low disk utilization method for precise liver CT segmentation. The proposed network is trained on medical segmentation decathlon dataset using a modified surface loss function. Additionally, we evaluate its quantitative and qualitative performance; the Res16-PAC-UNet achieves a Dice coefficient of 0.950 ± 0.019 with less than half a million parameters. Alternatively, the Res32-PAC-UNet obtains a Dice coefficient of 0.958 ± 0.015 with an acceptable parameter count of approximately 1.2 million., (© 2022. The Author(s).)

Vascular and inflammatory mechanisms are implicated in the development of cerebrovascular disease and corneal nerve loss occurs in patients with transient ischemic attack (TIA) and acute ischemic stroke (AIS). We have assessed whether serum markers of inflammation and vascular integrity are associated with the severity of corneal nerve loss in patients with TIA and AIS. Corneal confocal microscopy (CCM) was performed to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) in 105 patients with TIA (n = 24) or AIS (n = 81) and age matched control subjects (n = 56). Circulating levels of IL-6, MMP-2, MMP-9, E-Selectin, P-Selectin and VEGF were quantified in patients within 48 h of presentation with a TIA or AIS. CNFL (P = 0.000, P = 0.000), CNFD (P = 0.122, P = 0.000) and CNBD (P = 0.002, P = 0.000) were reduced in patients with TIA and AIS compared to controls, respectively with no difference between patients with AIS and TIA. The NIHSS Score (P = 0.000), IL-6 (P = 0.011) and E-Selectin (P = 0.032) were higher in patients with AIS compared to TIA with no difference in MMP-2 (P = 0.636), MMP-9 (P = 0.098), P-Selectin (P = 0.395) and VEGF (P = 0.831). CNFL (r = 0.218, P = 0.026) and CNFD (r = 0.230, P = 0.019) correlated with IL-6 and multiple regression analysis showed a positive association of CNFL and CNFD with IL-6 (P = 0.041, P = 0.043). Patients with TIA and AIS have evidence of corneal nerve loss and elevated IL6 and E-selectin levels. Larger longitudinal studies are required to determine the association between inflammatory and vascular markers and corneal nerve fiber loss in patients with cerebrovascular disease., (© 2022. The Author(s).)

Adverse drug events encompass a wide range of potential unintended and harmful events, from adverse drug reactions to medication errors, many of which in retrospect, are considered preventable. However, the primary challenge towards reducing their burden lies in consistently identifying and monitoring these occurrences, a challenge faced across the spectrum of healthcare, including the emergency medical services. The aim of this study was to identify and describe medication related adverse events (AEs) in the out-of-hospital setting. The medication components of a dedicated patient safety register were analysed and described for the period Jan 2017-Sept 2020. Univariate descriptive analysis was used to summarize and report on basic case and patient demographics, intervention related AEs, medication related AEs, and AE severity. Multivariable logistic regression was used to assess the odds of AE severity, by AE type. A total of 3475 patient records were assessed where 161 individual medication AEs were found in 150 (4.32%), 12 of which were categorised as harmful. Failure to provide a required medication was found to be the most common error (1.67%), followed by the administration of medications outside of prescribed practice guidelines (1.18%). There was evidence to suggest a 63% increase in crude odds of any AE severity [OR 1.63 (95% CI 1.03-2.6), p = 0.035] with the medication only AEs when compared to the intervention only AEs. Prehospital medication related adverse events remain a significant threat to patient safety in this setting and warrant greater widespread attention and future identification of strategies aimed at their reduction., (© 2022. The Author(s).)

Neurodevelopmental and neurodegenerative pathology occur in Schizophrenia. This study compared the utility of corneal confocal microscopy (CCM), an ophthalmic imaging technique with MRI brain volumetry in quantifying neuronal pathology and its relationship to cognitive dysfunction and symptom severity in schizophrenia. Thirty-six subjects with schizophrenia and 26 controls underwent assessment of cognitive function, symptom severity, CCM and MRI brain volumetry. Subjects with schizophrenia had lower cognitive function (P ≤ 0.01), corneal nerve fiber density (CNFD), length (CNFL), branch density (CNBD), CNBD:CNFD ratio (P < 0.0001) and cingulate gyrus volume (P < 0.05) but comparable volume of whole brain (P = 0.61), cortical gray matter (P = 0.99), ventricle (P = 0.47), hippocampus (P = 0.10) and amygdala (P = 0.68). Corneal nerve measures and cingulate gyrus volume showed no association with symptom severity (P = 0.35-0.86 and P = 0.50) or cognitive function (P = 0.35-0.86 and P = 0.49). Corneal nerve measures were not associated with metabolic syndrome (P = 0.61-0.64) or diabetes (P = 0.057-0.54). The area under the ROC curve distinguishing subjects with schizophrenia from controls was 88% for CNFL, 84% for CNBD and CNBD:CNFD ratio, 79% for CNFD and 73% for the cingulate gyrus volume. This study has identified a reduction in corneal nerve fibers and cingulate gyrus volume in schizophrenia, but no association with symptom severity or cognitive dysfunction. Corneal nerve loss identified using CCM may act as a rapid non-invasive surrogate marker of neurodegeneration in patients with schizophrenia., (© 2022. The Author(s).)

In patients with acute ischemic stroke, pial collaterals play a key role in limiting neurological disability by maintaining blood flow to ischemic penumbra. We hypothesized that patient with poor pial collaterals will have greater corneal nerve and endothelial cell abnormalities. In a cross-sectional study, 35 patients with acute ischemic stroke secondary to middle cerebral artery (MCA) occlusion with poor (n = 12) and moderate-good (n = 23) pial collaterals and 35 healthy controls underwent corneal confocal microscopy and quantification of corneal nerve and endothelial cell morphology. In patients with MCA stroke, corneal nerve fibre length (CNFL) (P < 0.001), corneal nerve fibre density (CNFD) (P = 0.025) and corneal nerve branch density (CNBD) (P = 0.002) were lower compared to controls. Age, BMI, cholesterol, triglycerides, HDL, LDL, systolic blood pressure, NIHSS and endothelial cell parameters did not differ but mRS was higher (p = 0.023) and CNFL (p = 0.026) and CNBD (p = 0.044) were lower in patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from moderate-good pial collaterals with an AUC of 72% (95% CI 53-92%) and 71% (95% CI 53-90%), respectively. Corneal nerve loss is greater in patients with poor compared to moderate-good pial collaterals and may act as a surrogate marker for pial collateral status in patients with ischemic stroke., (© 2021. The Author(s).)

The SARS-CoV-2 pandemic resulted in considerable morbidity and mortality as well as severe economic and societal disruptions. Despite scientific progress, true infection severity, factoring both diagnosed and undiagnosed infections, remains poorly understood. This study aimed to estimate SARS-CoV-2 age-stratified and overall morbidity and mortality rates based on analysis of extensive epidemiological data for the pervasive epidemic in Qatar, a country where < 9% of the population are ≥ 50 years. We show that SARS-CoV-2 severity and fatality demonstrate a striking age dependence with low values for those aged < 50 years, but rapidly growing rates for those ≥ 50 years. Age dependence was particularly pronounced for infection criticality rate and infection fatality rate. With Qatar's young population, overall SARS-CoV-2 severity and fatality were not high with < 4 infections in every 1000 being severe or critical and < 2 in every 10,000 being fatal. Only 13 infections in every 1000 received any hospitalization in acute-care-unit beds and < 2 in every 1000 were hospitalized in intensive-care-unit beds. However, we show that these rates would have been much higher if Qatar's population had the demographic structure of Europe or the United States. Epidemic expansion in nations with young populations may lead to considerably lower disease burden than currently believed., (© 2021. The Author(s).)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rising morbidity amongst hospitalized patients. Whilst clinical protocols for the management of individual DRESS cases have been well established, determination of potential prevention of these cases by utilizing novel "avoidability" tools has remained unexplored. This retrospective study reviewed records of patients who presented to the emergency department of Weill Cornell Medicine-affiliated Hamad General Hospital, Doha Qatar with suspected DRESS syndrome. These cases were independently adjudicated (utilizing the RegiSCAR, and JSCAR tools) as DRESS-drug pairs by a team of two clinical pharmacists and two General Physicians. They were then rated for potential avoidability with the Liverpool adverse drug reactions avoidability tool (LAAT) by the same team of raters. A total of 16 patients satisfied RegiSCAR criteria for DRESS syndrome. The mean age of the study population was 41.5 years (SD ± 13.3). The study population was predominantly male (n = 12; [75%]). The median latent period from drug ingestion to clinical presentation was 14 days (interquartile range [IQR] 6.5, 29). The median RegiSCAR and J-SCAR scores were 6 (IQR 5, 6.8), 5 (IQR 4, 5.8) respectively. Utilizing the LAAT, about 60% of the DRESS syndrome-drug pairs were rated as "avoidable" ("probable" or "definite"). The overall Krippendorf's alpha with the LAAT was 0.81 (SE 0.10, CI 0.59-1.00); with an intraclass correlation coefficient (ICC) of 0.90 (CI 0.77, 0.96.). In a randomly selected cohort of DRESS syndrome-drug pairs, a significant proportion was potentially avoidable ("possibly" and "definitely") utilizing the LAAT. This will need validation by larger sample-sized prospective studies utilizing the updated LAAT proposed by this study., (© 2021. The Author(s).)

Colorectal cancer (CRC) remains a global disease burden and a leading cause of cancer related deaths worldwide. The identification of aberrantly expressed messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), and the resulting molecular interactions and signaling networks is essential for better understanding of CRC, identification of novel diagnostic biomarkers and potential development of therapeutic interventions. Herein, we performed microRNA (miRNA) sequencing on fifteen CRC and their non-tumor adjacent tissues and whole transcriptome RNA-Seq on six paired samples from the same cohort and identified alterations in miRNA, mRNA, and lncRNA expression. Computational analyses using Ingenuity Pathway Analysis (IPA) identified multiple activated signaling networks in CRC, including ERBB2, RABL6, FOXM1, and NFKB networks, while functional annotation highlighted activation of cell proliferation and migration as the hallmark of CRC. IPA in combination with in silico prediction algorithms and experimentally validated databases gave insight into the complex associations and interactions between downregulated miRNAs and upregulated mRNAs in CRC and vice versa. Additionally, potential interaction between differentially expressed lncRNAs such as H19, SNHG5, and GATA2-AS1 with multiple miRNAs has been revealed. Taken together, our data provides thorough analysis of dysregulated protein-coding and non-coding RNAs in CRC highlighting numerous associations and regulatory networks thus providing better understanding of CRC., (© 2021. The Author(s).)

Regenerative endodontic procedures have gained momentum as a treatment modality of young immature permanent teeth. Literature reports reveal that platelet-rich fibrin (PRF) stimulates growth factors and induces regeneration. This study was undertaken to assess the regenerative potential of non-vital immature permanent maxillary central incisors using PRF with a follow-up for 2 yrs. 19 patients in the age group of 9-25 yrs with immature, non-vital permanent maxillary central incisors (n = 23) with/without signs and/or symptoms of periapical pathosis and open apex were included in this study. In the first appointment, access opening, canal disinfection and triple antibiotic paste placement were done. In the subsequent visit, PRF was prepared and placed inside the canal. Access was sealed with Mineral trioxide aggregate plug and composite. The patient was reviewed up to 24 mths. The mean difference was statistically analyzed using Friedman test followed by Dunn post hoc test and adjusted by Bonferroni correction (p < 0.05). As per AAE guidelines, the primary and secondary goals were achieved. A significant (p < 0.001) gradual increase in the root length, thickness of dentinal walls and decrease in apical diameter were observed. Within the limitations of this study, PRF placement was clinically and radiographically effective in inducing regeneration of non-vital immature permanent teeth.

The advent of personalised medicine promises a deeper understanding of mechanisms and therefore therapies. However, the connection between genomic sequences and clinical treatments is often unclear. We studied 50 breast cancer patients belonging to a population-cohort in the state of Qatar. From Sanger sequencing, we identified several new deleterious mutations in the estrogen receptor 1 gene (ESR1). The effect of these mutations on drug treatment in the protein target encoded by ESR1, namely the estrogen receptor, was achieved via rapid and accurate protein-ligand binding affinity interaction studies which were performed for the selected drugs and the natural ligand estrogen. Four nonsynonymous mutations in the ligand-binding domain were subjected to molecular dynamics simulation using absolute and relative binding free energy methods, leading to the ranking of the efficacy of six selected drugs for patients with the mutations. Our study shows that a personalised clinical decision system can be created by integrating an individual patient's genomic data at the molecular level within a computational pipeline which ranks the efficacy of binding of particular drugs to variant proteins.

Performance of three automated commercial serological IgG-based assays was investigated for assessing SARS-CoV-2 "ever" (past or current) infection in a population-based sample in a high exposure setting. PCR and serological testing was performed on 394 individuals. SARS-CoV-2-IgG seroprevalence was 42.9% (95% CI 38.1-47.8%), 40.6% (95% CI 35.9-45.5%), and 42.4% (95% CI 37.6-47.3%) using the CL-900i, VidasIII, and Elecsys assays, respectively. Between the three assays, overall, positive, and negative percent agreements ranged between 93.2-95.7%, 89.3-92.8%, and 93.8-97.8%, respectively; Cohen's kappa statistic ranged from 0.86 to 0.91; and 35 specimens (8.9%) showed discordant results. Among all individuals, 12.5% (95% CI 9.6-16.1%) had current infection, as assessed by PCR. Of these, only 34.7% (95% CI 22.9-48.7%) were seropositive by at least one assay. A total of 216 individuals (54.8%; 95% CI 49.9-59.7%) had evidence of ever infection using antibody testing and/or PCR during or prior to this study. Of these, only 78.2%, 74.1%, and 77.3% were seropositive in the CL-900i, VidasIII, and Elecsys assays, respectively. All three assays had comparable performance and excellent agreement, but missed at least 20% of individuals with past or current infection. Commercial antibody assays can substantially underestimate ever infection, more so when infection rates are high.

Euglycemic diabetic ketoacidosis (EuDKA) secondary to Sodium-glucose co-transporter-2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2D) is a rare but increasingly reported phenomenon. Not much is known about the burden of EuDKA in patients on SGLT2i or the associated factors. This retrospective cohort study tries to delineate the differences in factors associated with the development of EuDKA as compared to hyperglycemic DKA. We conducted a multicentre, retrospective study across three tertiary care centers under Weill Cornell affiliated-Hamad Medical Corporation, Qatar. The cohort comprised of T2D patients on SGLT2i who developed DKA between January 2015 to December 2020. The differences between the subjects who developed EuDKA or hyperglycaemic DKA (hDKA) were analyzed. A total of 9940 T2D patients were on SGLT2i during 2015-2020, out of which 43 developed DKA (0.43%). 25 developed EuKDA, whereas 18 had hDKA. The point prevalence of EuDKA in our cohort was 58.1%. EuDKA was most common in patients using canagliflozin, followed by empagliflozin and Dapagliflozin (100%, 77%, and 48.3%, respectively). Overall, infection (32.6%) was the most common trigger for DKA, followed by insulin non-compliance (13.7%). Infection was the only risk factor with a significant point estimate between the two groups, being more common in hDKA patients (p-value 0.006, RR 2.53, 95% CI 1.07-5.98). Canagliflozin had the strongest association with the development of EuDKA and was associated with the highest medical intensive care unit (MICU) admission rates (66.6%). In T2D patients on SGLT2i, infection is probably associated with an increased risk of developing EuDKA. The differential role of individual SGLT2i analogs is less clear and will need exploration by more extensive prospective studies.

Tocilizumab (TCZ) and Dexamethasone are used for the treatment of critically ill COVID-19 patients. We compared the short-term survival of critically ill COVID-19 patients treated with either TCZ or Dexamethasone. 109 critically ill COVID-19 patients randomly assigned to either TCZ therapy (46 patients) or pulse Dexamethasone therapy (63 patients). Age, sex, neutrophil/ lymphocyte ratio, D-dimer, ferritin level, and CT chest pattern were comparable between groups. Kaplan-Meier survival analysis showed better survival in Dexamethasone group compared with TCZ (P = 0.002), patients didn't need vasopressor at admission (P < 0.0001), patients on non-invasive ventilation compared to patients on mechanical ventilation (P<0.0001 ), and in patients with ground glass pattern in CT chest (P<0.0001 ) compared with those who have consolidation. Cox regression analysis showed that, TCZ therapy (HR = 2.162, 95% CI, 1.144-4.087, P <0.0001) compared with Dexamethasone group, higher neutrophil/Lymphocyte ratio (HR = 2.40, CI, 1.351-4.185, P = 0.003), lower PaO 2 /FiO 2 , 2 days after treatment, (HR = 1.147, 95% CI, 1.002-1.624, P < 0.0001) independently predicted higher probability of mortality. Dexamethasone showed better survival in severe COVID-19 compared to TCZ. Considering the risk factors mentioned here is crucial when dealing with severe COVID-19 cases.Clinical trial registration No clinicalTrials.gov: Nal protocol approved by Hospital Authorities, for data collection and for participation in CT04519385 (19/08/2020).

The prevalence and incidence of diabetes mellitus (DM) are increasing worldwide. We aim to assess mortality and socio-economic outcomes among patients hospitalized for stroke and diabetes in the US and evaluate their recent trends. We examined: in-hospital mortality, length of stay (LoS), and overall hospital charges in diabetic patients over 18 years old who were hospitalized with a stroke from 2005 to 2014, included in the National Inpatient Sample. In those patients, the mean (SD) age slightly decreased from 70 (13) years to 69 (13) years (p-trend < 0.001). Interestingly, although incident cases of stroke amongst DM patients increased from 17.4 to 20.0 /100,000 US adults (p-trend < 0.001), age-adjusted mortality for those with hemorrhagic strokes decreased from 24.3% to 19.6%, and also decreased from 3.23% to 2.48% for those with ischemic strokes (p-trend < 0.01 for both), but remained unchanged in TIAs patients. As expected, the average total charges per hospital stay almost doubled over the ten-year period, increasing from 15 970 to 31 018 USD/stay (adjusted for inflation). Nonetheless, median (IQR) LoS slightly decreased from 4 (2-6) to 3 (2-6) days (p-trend < 0.001). In total, our data show that, from 2005 to 2014, the incidence of stroke among the diabetes patient population are gradually increasing, in-hospital mortality is steadily decreasing, along with average LoS. Admission costs were up almost twofold during the same period.

The NAD + -dependent deacetylase SIRT1 controls key metabolic functions by deacetylating target proteins and strategies that promote SIRT1 function such as SIRT1 overexpression or NAD + boosters alleviate metabolic complications. We previously reported that SIRT1-depletion in 3T3-L1 preadipocytes led to C-Myc activation, adipocyte hyperplasia, and dysregulated adipocyte metabolism. Here, we characterized SIRT1-depleted adipocytes by quantitative mass spectrometry-based proteomics, gene-expression and biochemical analyses, and mitochondrial studies. We found that SIRT1 promoted mitochondrial biogenesis and respiration in adipocytes and expression of molecules like leptin, adiponectin, matrix metalloproteinases, lipocalin 2, and thyroid responsive protein was SIRT1-dependent. Independent validation of the proteomics dataset uncovered SIRT1-dependence of SREBF1c and PPARα signaling in adipocytes. SIRT1 promoted nicotinamide mononucleotide acetyltransferase 2 (NMNAT2) expression during 3T3-L1 differentiation and constitutively repressed NMNAT1 and 3 levels. Supplementing preadipocytes with the NAD + booster nicotinamide mononucleotide (NMN) during differentiation increased expression levels of leptin, SIRT1, and PGC-1α and its transcriptional targets, and reduced levels of pro-fibrotic collagens (Col6A1 and Col6A3) in a SIRT1-dependent manner. Investigating the metabolic impact of the functional interaction of SIRT1 with SREBF1c and PPARα and insights into how NAD + metabolism modulates adipocyte function could potentially lead to new avenues in developing therapeutics for obesity complications.

The overarching objective of this study was to provide the descriptive epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Qatar by addressing specific research questions through a series of national epidemiologic studies. Sources of data were the centralized and standardized national databases for SARS-CoV-2 infection. By July 10, 2020, 397,577 individuals had been tested for SARS-CoV-2 using polymerase-chain-reaction (PCR), of whom 110,986 were positive, a positivity cumulative rate of 27.9% (95% CI 27.8-28.1%). As of July 5, case severity rate, based on World Health Organization (WHO) severity classification, was 3.4% and case fatality rate was 1.4 per 1,000 persons. Age was by far the strongest predictor of severe, critical, or fatal infection. PCR positivity of nasopharyngeal/oropharyngeal swabs in a national community survey (May 6-7) including 1,307 participants was 14.9% (95% CI 11.5-19.0%); 58.5% of those testing positive were asymptomatic. Across 448 ad-hoc testing campaigns in workplaces and residential areas including 26,715 individuals, pooled mean PCR positivity was 15.6% (95% CI 13.7-17.7%). SARS-CoV-2 antibody prevalence was 24.0% (95% CI 23.3-24.6%) in 32,970 residual clinical blood specimens. Antibody prevalence was only 47.3% (95% CI 46.2-48.5%) in those who had at least one PCR positive result, but 91.3% (95% CI 89.5-92.9%) among those who were PCR positive > 3 weeks before serology testing. Qatar has experienced a large SARS-CoV-2 epidemic that is rapidly declining, apparently due to growing immunity levels in the population.

Prescription opioid use (POU) is often a precursor to opioid use disorder (OUD) and subsequent consequences. Persons with chronic hepatitis C virus infection (CHC) may be at a higher risk of POU due to a higher comorbidity burden and social vulnerability factors. We sought to determine the burden of POU and associated risk factors among persons with CHC in the context of social vulnerability. We identified CHC persons and propensity-score matched HCV- controls in the electronically retrieved Cohort of HCV-Infected Veterans and determined the frequency of acute, episodic long-term and chronic long-term POU and the prevalence of social vulnerability factors among persons with POU. We used logistic regression analysis to determine factors associated with POU. Among 160,856 CHC and 160,856 propensity-score matched HCV-controls, acute POU was recorded in 38.4% and 38.0% (P = 0.01) respectively. Episodic long-term POU was recorded in 3.9% in each group (P = 0.5), while chronic long-term POU was recorded in 28.4% and 19.2% (P < 0.0001). CHC was associated with a higher risk of chronic long-term POU (OR 1.66, 95%CI 1.63, 1.69), but not with acute or episodic long-term POU. Black race, female sex and homelessness were associated with a higher risk of chronic long-term POU. Presence of ≥ 1 factor was associated with a higher risk of all POU patterns. Persons with CHC have more social vulnerability factors and a higher risk of chronic long-term POU. Presence of ≥ 1 social vulnerability factor is associated with a higher risk of POU. Downstream consequences of POU need further study.

There are currently several diagnostic criteria for gestational diabetes (GDM). Both the WHO -2013 and NICE diagnose GDM based on a single step 75 g OGT; however; each uses different glucose thresholds. Previous studies have shown that the prevalence of GDM using the NICE criteria (GDM-N) is lower than that using the WHO-2013 criteria (GDM-W). Qatar has national diabetes in pregnancy program in which all pregnant women undergo OGTT screening using the WHO-2013 criteria. This study aims to define the prevalence of GDM using both criteria in a high-risk population. This retrospective study included 2000 women who underwent a 75 g (OGTT) between Jan 2016 and Apr 2016 and excluded patients with known pre-conception diabetes, multiple pregnancy, and those who did not complete the OGTT. We then classified the women into GDM-W positive, GDM-N positive but GDM-W negative, and normal glucose tolerance (NGT) population. A total of 1481 women (74%) had NGT using the NICE or the WHO-2013 criteria. The number of patients who met both criteria was 279 subjects (14%) with a good agreement (Kappa coefficient 0.67, p < 0.001). The NICE and the WHO-2013 criteria were discordant in 240 subjects (12% of the cohort); 6.7% met the WHO -2013 criteria only and only 5.3% met the NICE criteria. The frequency of pre-eclampsia, pre-term delivery, Caesarean-section, LGA and neonatal ICU admissions were significantly increased in the GDM-W group. However, the GDM-N positive but GDM-W negative had no increased risk of maternal or fetal complications apart from pregnancy-induced hypertension. The WHO-2013 and the NICE criteria classified a similar proportion of pregnant women, 21.5% and 20.1%, respectively, as having GDM; however, they were concordant in only 14% of the cases. Women who are GDM-N positive but GDM-W negative are not at increased risk of maternal and fetal pregnancy complications, except for pregnancy-induced hypertension. As the NICE criteria are more specific to the UK population, we would recommend the use of the WHO-2013 criteria to diagnose GDM in the MENA region and possibly other regions that do not have the same set-up as the UK.

The aim of the current study is to review the molecular characteristics of Neisseria meningitidis (N. meningitidis) in Hamad Medical Corporation, which is the provider of secondary and tertiary care in the state of Qatar. A total of 39 isolates of N. meningitidis from the period of 2013 to 2018 were revived and identified by Vitek, and susceptibility on the basis of the E test was retrieved from the patient's files. The revived isolates were subjected to multilocus sequence typing. The most common serogroup (19) of N. meningitidis was W135, of which 12 were isolated from blood and CSF. ST-11 was the most predominant ST clonal complex causing N. meningitidis cases (61.53%). Clonal complex ST-41/44 was the second most observed complex (3, 2 of which were related to serogroup B). The most frequent sequence type was 9596 (8 isolates). Determining the molecular pattern of N. meningitidis in Qatar is helpful for understanding the strains circulating in Qatar, and the study of the resistance trend of such strains may be very helpful for empirical treatment of future patients.

Implementing the principles of tissue engineering within the clinical management of non-vital immature permanent teeth is of clinical interest. However, the ideal scaffold remains elusive. The aim of this work was to assess the feasibility of decellularising rat dental pulp tissue and evaluate the ability of such scaffold to support stem cell repopulation. Rat dental pulps were retrieved and divided into control and decellularised groups. The decellularisation protocol incorporated a low detergent concentration and hypotonic buffers. After decellularisation, the scaffolds were characterised histologically, immunohistochemistry and the residual DNA content quantified. Surface topography was also viewed under scanning electron microscopy. Biocompatibility was evaluated using cytotoxicity assays utilising L-929 cell line. Decellularised scaffolds were recellularised with human dental pulp stem cells up to 14 days in vitro. Cellular viability was assessed using LIVE/DEAD stain kit and the recellularised scaffolds were further assessed histologically and immunolabelled using makers for odontoblastic differentiation, cytoskeleton components and growth factors. Analysis of the decellularised scaffolds revealed an acellular matrix with histological preservation of structural components. Decellularised scaffolds were biocompatible and able to support stem cell survival following recellularisation. Immunolabelling of the recellularised scaffolds demonstrated positive cellular expression against the tested markers in culture. This study has demonstrated the feasibility of developing a biocompatible decellularised dental pulp scaffold, which is able to support dental pulp stem cell repopulation. Clinically, decellularised pulp tissue could possibly be a suitable scaffold for use within regenerative (reparative) endodontic techniques.

To determine if metabolic characteristics differed in women with and without polycystic ovary syndrome (PCOS) between a Caucasian and Middle East population. Comparative cross-sectional analysis. Demographic and metabolic data from Middle Eastern women from Qatar Biobank (97 with PCOS, 622 controls) were compared to a Caucasian PCOS biobank in Hull UK (108 with PCOS, 69 controls). In both populations, PCOS women showed a worse cardiovascular risk profile of increased systolic and diastolic blood pressure, increased C-reactive protein (CRP), reduced HDL, insulin resistance as well as increased androgens compared to their respective controls without PCOS. UK women without PCOS had higher systolic and diastolic blood pressures, and increased testosterone results (p < 0.01) compared to Middle Eastern women without PCOS who had higher inflammatory markers (WBC and CRP), HDL and insulin resistance (p < 0.001). UK PCOS women had a higher body mass index, systolic and diastolic blood pressures, triglycerides (p < 0.01), whilst Middle Eastern PCOS women showed increased testosterone, free androgen index, HDL and CRP (P < 0.01). There was no difference in insulin or insulin resistance between the two PCOS cohorts. This study highlights ethnic population differences because, whilst cardiovascular risk indices were increased for both PCOS cohorts, this may be for different reasons: BMI, waist and hip measurements, systolic and diastolic blood pressure, and triglycerides were higher in the UK cohort whilst testosterone, HDL and CRP were higher in the Middle East population. Insulin resistance did not differ between the two PCOS populations despite differences in BMI.

Metabolic pathways that are corrupted at early stages of insulin resistance (IR) remain elusive. This study investigates changes in body metabolism in clinically healthy and otherwise asymptomatic subjects that may become apparent already under compromised insulin sensitivity (IS) and prior to IR. 47 clinically healthy Arab male subjects with a broad range of IS, determined by hyperinsulinemic-euglycemic clamp (HIEC), were investigated. Untargeted metabolomics and complex lipidomics were conducted on serum samples collected under fasting and HIEC conditions. Linear models were used to identify associations between metabolites concentrations and IS levels. Among 1896 identified metabolites, 551 showed significant differences between fasting and HIEC, reflecting the metabolic switch in energy utilization. At fasting, 336 metabolites, predominantly di- and tri-acylglycerols, showed significant differences between subjects with low and high levels of IS. Changes in amino acid, carbohydrate and fatty acid metabolism in response to insulin were impaired in subjects with low IS. Association of altered mannose and amino acids with IS was also replicated in an independent cohort of T2D patients. We identified metabolic phenotypes that characterize clinically healthy Arab subjects with low levels of IS at their fasting state. Our study is providing further insights into the metabolic pathways that precede IR.

Beta-blockers (BB) have been traditionally associated with improvement in cardiovascular disease outcomes in patients with ischemic cardiomyopathy. Whether they're still efficacious in the post-reperfusion era is currently debated in the light of recent controversial reports. In-hospital, 6-month and 12-month mortality were studied in the GULF-COAST, a prospective multicenter cohort of acute coronary syndrome (ACS), in relation to BB use: prior to admission, 24-hour post-admission and on discharge in patients with a left ventricular ejection fraction (LVEF) ≥ 40%. On admission, 50.9% of the cohort participants had a LVEF ≥ 40%, of whom 1203 (55.4%) were on BB whilst 905 (44.6%) were not. Mean age was 60 (13) years old and 66% were males. Prior BB use or its administration in 24 hours decreased in-hospital mortality (OR = 0.25, 95% CI [0.09-0.67]; OR = 0.16, 95% CI [0.08-0.35]; respectively). BB on discharge lowered 1-month mortality (OR = 0.28, 95% CI [0.11-0.72]), but had a neutral effect on mortality, reinfarction and stroke at 6 and 12 months. Results were unchanged after multivariable adjustments and further sensitivity analysis. In this retrospective cohort of ACS, BB improved in-hospital and 1-month mortality in patients with a LVEF ≥ 40% but had a neutral effect on longer-term outcome.

Malignant middle cerebral artery [MMCA] infarction has a different topographic distribution that might confound the relationship between lesion volume and outcome. Retrospective study to determine the multivariable relationship between computerized tomographic [CT] infarct location, volume and outcomes in decompressive hemicraniectomy [DHC] for MMCA infarction. The MCA infarctions were classified into four subgroups by CT, subtotal, complete MCA [co-MCA], Subtotal MCA with additional infarction [Subtotal MCAAI] and co-MCA with additional infarction [Co-MCAAI]. Maximum infarct volume [MIV] was measured on the pre-operative CT. Functional outcome was measured by the modified Rankin Scale [mRS] dichotomized as favourable 0-3 and unfavourable ≥4, at three months. In 137 patients, from least favourable to favourable outcome were co-MCAAI, subtotal MCAAI, co-MCA and subtotal MCA infarction. Co-MCAAI had the worst outcome, 56/57 patients with additional infarction had mRS ≥ 4. Multiple comparisons Scheffe test showed no significant difference in MIV of subtotal infarction, co-MCA, Subtotal MCAAI but the outcome was significantly different. Multivariate analysis confirmed MCAAI [7.027 (2.56-19.28), p = 0.000] as the most significant predictor of poor outcomes whereas MIV was not significant [OR, 0.99 (0.99-01.00), p = 0.594]. Other significant independent predictors were age ≥ 55 years 12.14 (2.60-56.02), p = 0.001 and uncal herniation 4.98(1.53-16.19), p = 0.007]. Our data shows the contribution of CT infarction location in determining the functional outcome after DHC. Subgroups of patients undergoing DHC had different outcomes despite comparable infarction volumes.

The effectiveness of dapagliflozin in the management of type-2 diabetes mellitus (T2-DM) is an essential issue for establishing a basis for prescribing dapagliflozin. This study aimed to assess the effectiveness of dapagliflozin in combination with other hypoglycemic agents (OHAs) in reducing glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) at 3, 6, 9 and 12 months. This retrospective observational study included all patients who visited the endocrine clinics at Hamad Medical Corporation (HMC) and were treated with dapagliflozin. Demographics and laboratory data were obtained retrospectively from computerized patient medical profiles (eMR-viewer). The main outcome measures were the differences in HbA1c and FBG from baseline at different months. Eighty-one Qatari patients were found to have received dapagliflozin during the study period; 72% of them (n = 58) were males, with a mean age of 57.0 ± 9.0 years and a mean baseline HbA1c of 9.0 ± 1.4%. Administration of dapagliflozin as an add-on therapy was found to decrease HbA1c significantly by 0.8 percentage point after 6 months (P = 0.006) and by 1.5 percentage point after 12 months (P = 0.062). FBG was significantly reduced at 6 months and 9 months (P = 0.001 and P = 0.03, respectively). Dapagliflozin effectively reduced the HbA1c level and FBG when used in combination with other OHAs or insulin within 6 to 12 months.

Failure of the heat shock response is a key event that leads to insulin resistance and type 2 diabetes. We recently showed that DNAJB3 co-chaperone is downregulated in obese and diabetic patients and that physical exercise restores its normal expression with a significant improvement of the clinical outcomes. In 3T3-L1 adipocytes, DNAJB3 has a role in improving the sensitivity to insulin and glucose uptake. In co-immunoprecipitation assays, DNAJB3 interacts with both JNK1 and IKKβ kinases. However, the functional impact of such interaction on their activities has not been investigated. Here, we assessed the effect of DNAJB3 on the respective activity of JNK1 and IKKβ in cell-based assays. Using JNK1- and IKKβ-dependent luciferase reporters, we show a marked decrease in luciferase activity by DNAJB3 in response to PMA and TNF-α that was consistent with a decrease in the translocation of p65/NF-κB to the nucleus in response to LPS. Furthermore, TNF-α-mediated IL-6 promoter activation and endogenous mRNA expression are significantly abrogated by DNAJB3 both in 3T3-L1 and C2C12 cells. The ability of DNAJB3 to mitigate ER stress and oxidative stress was also investigated and our data show a significant improvement of both forms of stress. Finally, we examined the effect of overexpressing and knocking down the expression of DNAJB3 on glucose uptake in C2C12 as well as the molecular determinants. Accordingly, we provide evidence for a role of DNAJB3 in promoting both basal and insulin-stimulated glucose uptake. Our finding reveals also a novel role of DNAJB3 in eliciting Glut4 translocation to the plasma membrane. These results suggest a physiological role of DNAJB3 in mitigating metabolic stress and improving glucose homeostasis and could therefore represent a novel therapeutic target for type 2 diabetes.

Patients treated during leukemia face the risk of complications including pulmonary dysfunction that may result from infiltration of leukemic blast cells (LBCs) into lung parenchyma and interstitium. In LBCs, we demonstrated that transient receptor potential vanilloid type 2 channel (TRPV2), reputed for its role in inflammatory processes, exhibited oncogenic activity associated with alteration of its molecular expression profile. TRPV2 was overexpressed in LBCs compared to normal human peripheral blood mononuclear cells (PBMCs). Additionally, functional full length isoform and nonfunctional short form pore-less variant of TRPV2 protein were up-regulated and down-regulated respectively in LBCs. However, the opposite was found in PBMCs. TRPV2 silencing or pharmacological targeting by Tranilast (TL) or SKF96365 (SKF) triggered caspace-mediated apoptosis and cell cycle arrest. TL and SKF inhibited chemotactic peptide fMLP-induced response linked to TRPV2 Ca 2+ activity, and down-regulated expression of surface marker CD38 involved in leukemia and lung airway inflammation. Challenging lung airway epithelial cells (AECs) with LBCs decreased (by more than 50%) transepithelial resistance (TER) denoting barrier function alteration. Importantly, TL prevented such loss in TER. Therefore, TRPV2 merits further exploration as a pharmacodynamic biomarker for leukemia patients (with pulmonary inflammation) who might be suitable for a novel [adjuvant] therapeutic strategy based on TL.

Endothelial dysfunction and damage underlie cerebrovascular disease and ischemic stroke. We undertook corneal confocal microscopy (CCM) to quantify corneal endothelial cell and nerve morphology in 146 patients with an acute ischemic stroke and 18 age-matched healthy control participants. Corneal endothelial cell density was lower (P < 0.001) and endothelial cell area (P < 0.001) and perimeter (P < 0.001) were higher, whilst corneal nerve fibre density (P < 0.001), corneal nerve branch density (P < 0.001) and corneal nerve fibre length (P = 0.001) were lower in patients with acute ischemic stroke compared to controls. Corneal endothelial cell density, cell area and cell perimeter correlated with corneal nerve fiber density (P = 0.033, P = 0.014, P = 0.011) and length (P = 0.017, P = 0.013, P = 0.008), respectively. Multiple linear regression analysis showed a significant independent association between corneal endothelial cell density, area and perimeter with acute ischemic stroke and triglycerides. CCM is a rapid non-invasive ophthalmic imaging technique, which could be used to identify patients at risk of acute ischemic stroke.

Distant metastasis is the major cause of death in colorectal cancer (CRC). Patients at high risk of developing distant metastasis could benefit from appropriate adjuvant and follow-up treatments if stratified accurately at an early stage of the disease. Studies have increasingly recognized the role of diverse cellular components within the tumor microenvironment in the development and progression of CRC tumors. In this paper, we show that automated analysis of digitized images from locally advanced colorectal cancer tissue slides can provide estimate of risk of distant metastasis on the basis of novel tissue phenotypic signatures of the tumor microenvironment. Specifically, we determine what cell types are found in the vicinity of other cell types, and in what numbers, rather than concentrating exclusively on the cancerous cells. We then extract novel tissue phenotypic signatures using statistical measurements about tissue composition. Such signatures can underpin clinical decisions about the advisability of various types of adjuvant therapy.

Determining the grade of colon cancer from tissue slides is a routine part of the pathological analysis. In the case of colorectal adenocarcinoma (CRA), grading is partly determined by morphology and degree of formation of glandular structures. Achieving consistency between pathologists is difficult due to the subjective nature of grading assessment. An objective grading using computer algorithms will be more consistent, and will be able to analyse images in more detail. In this paper, we measure the shape of glands with a novel metric that we call the Best Alignment Metric (BAM). We show a strong correlation between a novel measure of glandular shape and grade of the tumour. We used shape specific parameters to perform a two-class classification of images into normal or cancerous tissue and a three-class classification into normal, low grade cancer, and high grade cancer. The task of detecting gland boundaries, which is a prerequisite of shape-based analysis, was carried out using a deep convolutional neural network designed for segmentation of glandular structures. A support vector machine (SVM) classifier was trained using shape features derived from BAM. Through cross-validation, we achieved an accuracy of 97% for the two-class and 91% for three-class classification.

Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.