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Background Aspirin is widely used as a cardioprotective agent due to its antiplatelet and anti-inflammatory properties. The literature has assessed and evaluated its role in hospitalized COVID-19 patients. However, no data are available regarding its role in COVID-19 critically ill patients. This study aimed to evaluate the use of low-dose aspirin (81-100 mg) and its impact on outcomes in critically ill patients with COVID-19. Method A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to intensive care units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on aspirin use during ICU stay. The primary outcome was in-hospital mortality, and other outcomes were considered secondary. Propensity score matching was used (1:1 ratio) based on the selected criteria. Results A total of 1033 patients were eligible, and 352 patients were included after propensity score matching. The in-hospital mortality (HR 0.73 [0.56, 0.97], p = 0.03) was lower in patients who received aspirin during stay. Conversely, patients who received aspirin had a higher odds of major bleeding than those in the control group (OR 2.92 [0.91, 9.36], p = 0.07); however, this was not statistically significant. Additionally, subgroup analysis showed a possible mortality benefit for patients who used aspirin therapy prior to hospitalization and continued during ICU stay (HR 0.72 [0.52, 1.01], p = 0.05), but not with the new initiation of aspirin (HR 1.22 [0.68, 2.20], p = 0.50). Conclusion Continuation of aspirin therapy during ICU stay in critically ill patients with COVID-19 who were receiving it prior to ICU admission may have a mortality benefit; nevertheless, it may be associated with an increased risk of significant bleeding. Appropriate evaluation for safety versus benefits of utilizing aspirin therapy during ICU stay in COVID19 critically ill patients is highly recommended.

Bidirectional Encoder Representations from Transformers (BERT) and BERT-based approaches are the current state-of-the-art in many natural language processing (NLP) tasks; however, their application to document classification on long clinical texts is limited. In this work, we introduce four methods to scale BERT, which by default can only handle input sequences up to approximately 400 words long, to perform document classification on clinical texts several thousand words long. We compare these methods against two much simpler architectures - a word-level convolutional neural network and a hierarchical self-attention network - and show that BERT often cannot beat these simpler baselines when classifying MIMIC-III discharge summaries and SEER cancer pathology reports. In our analysis, we show that two key components of BERT - pretraining and WordPiece tokenization - may actually be inhibiting BERT's performance on clinical text classification tasks where the input document is several thousand words long and where correctly identifying labels may depend more on identifying a few key words or phrases rather than understanding the contextual meaning of sequences of text.

Evaluating the knowledge of patients attending radiology departments regarding ionizing radiation used in medical imaging and its associated hazards can provide knowledge of the patient's awareness level of the associated risk of the radiation used in medical imaging. The aims of this study were to evaluate the awareness of patients regarding medical radiation types used in medical diagnostic imaging and its influence on their decision to proceed with that procedure. Over an 8-months period, a total of 418 patients, 48% Men and 52% Women, presenting for diagnostic imaging in the department of radiology, completed a 15-point questionnaire. The questionnaire included demographic and radiation awareness sections. Less than 32% of the participants had a potential risk of radiation explained by the doctor before the procedure. 59% of the participants expressed that the potential risk of radiation makes them anxious; less than about 25% of the participants showed that the potential risk of radiation affects their decision to have the procedure. Overall, the data collected from this survey indicate that there is a lack of information about radiation risk provided to the patients prior to the diagnostic procedure. Efforts should be made to ensure that patients receiving multiple medical imaging tests are aware of the radiation they are receiving.

Early in the SARS-CoV-2 pandemic, convalescent plasma (CP) therapy was proposed as a treatment for severely ill patients. We conducted a CP treatment protocol under the Mayo Clinic Extended Access Program at University Hospital Brooklyn (UHB). Potential donors were screened with a lateral flow assay (LFA) for IgM and IgG antibodies against the SARS-CoV-2 S1 receptor-binding domain (RBD). Volunteers that were LFA positive were tested with an ELISA to measure IgG titers against the RBD. Subjects with titers of at least 1:1024 were selected to donate. Most donors with positive LFA had acceptable titers and were eligible to donate. Out of 171 volunteers, only 65 tested positive in the LFA (38.0%), and 55 (32.2%) had titers of at least 1:1024. Before our donation program started, 31 CP units were procured from the New York Blood Center (NYBC). Among the 31 CP units that were obtained from the NYBC, 25 units (80.6%) were positive in the LFA but only 12 units (38.7%) had titers of at least 1:1024. CP was administered to 28 hospitalized COVID-19 patients. Patients who received low titer CP, high titer CP and patients who did not receive CP were followed for 45 days after presentation. Severe adverse events were not associated with CP transfusion. Death was a less frequent outcome for patients that received high titer CP (>1:1024) 38.6% mortality, than patients that received low titer CP (≤1:1024) 77.8% mortality.

Background The incidence of ectopic kidneys is 1:12,000 clinically and 1:900 postmortem. Patients with pelvic mal-rotated kidneys are more susceptible to recurrent urinary tract infections, recurrent renal stones, and renal injury. Fusion of the kidney lower poles is relatively common compared to other types of renal anomalies. Case presentation We present the case of a 36-year-old Sudanese female patient who presented with a long history of recurrent urinary tract infections unresponsive to antibiotics. Ultrasound scan revealed bilateral pelvic kidneys. Computed tomography (CT) urography confirmed bilateral ectopic fused kidneys, with the left kidney mal-rotated (renal pelvis facing upwards and laterally). Kidney infection secondary to vesicoureteral reflux was diagnosed. Antibiotics were prescribed according to culture and sensitivity. The patient responded well to ciprofloxacin. Conclusion A history of recurrent urinary tract infections without an apparent cause is highly suggestive of renal anomaly and should be investigated expediently. Ultrasonography or CT imaging may be utilized to aid in diagnosis. Early recognition may help prevent the high risk of end-stage renal failure associated with anomalies.

BackgroundAutomated text classification has many important applications in the clinical setting; however, obtaining labelled data for training machine learning and deep learning models is often difficult and expensive. Active learning techniques may mitigate this challenge by reducing the amount of labelled data required to effectively train a model. In this study, we analyze the effectiveness of 11 active learning algorithms on classifying subsite and histology from cancer pathology reports using a Convolutional Neural Network as the text classification model.ResultsWe compare the performance of each active learning strategy using two differently sized datasets and two different classification tasks. Our results show that on all tasks and dataset sizes, all active learning strategies except diversity-sampling strategies outperformed random sampling, i.e., no active learning. On our large dataset (15K initial labelled samples, adding 15K additional labelled samples each iteration of active learning), there was no clear winner between the different active learning strategies. On our small dataset (1K initial labelled samples, adding 1K additional labelled samples each iteration of active learning), marginal and ratio uncertainty sampling performed better than all other active learning techniques. We found that compared to random sampling, active learning strongly helps performance on rare classes by focusing on underrepresented classes.ConclusionsActive learning can save annotation cost by helping human annotators efficiently and intelligently select which samples to label. Our results show that a dataset constructed using effective active learning techniques requires less than half the amount of labelled data to achieve the same performance as a dataset constructed using random sampling.

Objectives The decline in diarrhoeal disease-related mortality globally has been attributed to the use of oral rehydration solution (ORS) and zinc supplementation. However, data on ORS and zinc supplementation in Sudan are scarce. We aimed to investigate the access to ORS and zinc treatments and the associated factors, through the analysis of the latest available data from Sudan-Multiple Indicator Cluster Survey (MICS)-2014 obtained from the United Nations Children’s Fund (UNICEF). Results A total of 14,081 children were included in this analysis. During the 2 weeks preceding the survey, 29.3% of these children had a diarrhoeal disease. Only 18.9% and 14.8% of these children had received ORS and zinc supplements, respectively. Whereas children from the higher wealth index groups were more likely to receive ORS treatment (fourth group: AOR = 1.301; 95% CI 1.006–1.682), children from rural areas were less likely to receive ORS treatment (AOR = 0.666; 95% CI 0.552–0.803) and zinc supplements (AOR = 0.603; 95% CI 0.500–0.728). The results indicate the existence of unequal access to treatment of childhood diarrhoeal diseases among children under 5 years in Sudan.

Objective:The aim of this study was to evaluate the readiness of a tertiary medical cityʼs response to a disaster by assessing the hospital resources and knowledge, attitudes, practices, and familiarity of health care providers toward disaster and emergency preparedness.Methods:All KFMC (King Fahad Medical City) staff with > 1 year of clinical experience were eligible to participate in a cross-sectional study. Participants responded to the Emergency Preparedness Information Questionnaire (EPIQ), knowledge and practice questionnaires, and a disaster planning attitude checklist. Data about resources were collected using the hospital disaster preparedness self-assessment tool.Results:The overall mean knowledge score for disaster and emergency preparedness was 4.4 ± 1.1, and the mean overall familiarity score was 3.43 ± 0.97. Most participants knew that disaster drills (90.2%) and training (74.6%) are ongoing. Sixty-six (21.0%) agreed that KFMC is unlikely to experience a disaster. The highest and lowest EPIQ familiarity scores were for decontamination (83.0%) and accessing critical resources and reporting (64.3%), respectively. Most participants (99.4%) have access to work computers; however, only 53.0% used the Internet to access information on bioterrorism and/or emergency preparedness. The hospital is ready to respond in case of a disaster according to the used tool.Conclusions:The participants’ levels of knowledge, practices, and overall familiarity toward emergency and disaster preparedness were satisfactory; however, participant attitudes and familiarity with where and how to access critical resources in the event of an emergency or disaster situations require reinforcement.

BackgroundCOVID-19 is a respiratory disease caused by SARS-CoV-2, a new coronavirus discovered in December 2019 in China. COVID-19 symptoms are similar to those of viral flu but may be more severe, these symptoms can be defended by vaccines, the most distributed 6 candidate vaccines are Pfizer, BioNTech, Moderna, Johnson & Johnson/Janssen AstraZeneca, Sinopharm, Sinovac. In Sudan, the virus has rapidly spread in the country, causing a total of 37,138 confirmed cases with 2,776 deaths till July 21, 2021. We are targeting health workers, medical students, and the general public to assess their behavior regarding COVID-19 vaccines in Sudan, recognize the determinants of their behavior, and identify the factors increasing vaccine acceptance among them.MethodsWe conducted a pretested cross-sectional online survey involving healthcare workers, medical students, and the general population in Sudan in July and August. We collected the data by sending the survey to social media platforms (e.g., Facebook and WhatsApp). The survey was conducted anonymously without identity-related data. We used both convenience sampling and snowball sampling methods as the participants were asked to forward the survey link to their contacts. The sample size was calculated using Slovin's formula and we estimated the sample size to be 400.ResultsOf our 400 participants, 36.8% (n = 147) were males and 63.2% (n = 253) were females, the mean age of the participants was 24.17 ± 8.07. The overall vaccine acceptance rate was 48.2% (n = 193) and “Occupation” was the only sociodemographic domain significantly associated with vaccine acceptance, showing a higher acceptance rate among health care workers (p = 0.009). “Afraid of unknown side effects” was the most commonly reported barrier to vaccination (p = 0.33).ConclusionThe vaccine acceptance rate is low, and public health authorities and the government in Sudan have a heavy mission for implementing successful vaccination programs with high coverage.

Cytogenetics laboratory tests are among the most important procedures for the diagnosis of genetic diseases, especially in the area of hematological malignancies. Manual chromosomal karyotyping methods are time consuming and labor intensive and, hence, expensive. Therefore, to alleviate the process of analysis, several attempts have been made to enhance karyograms. The current chromosomal image enhancement is based on classical image processing. This approach has its limitations, one of which is that it has a mandatory application to all chromosomes, where customized application to each chromosome is ideal. Moreover, each chromosome needs a different level of enhancement, depending on whether a given area is from the chromosome itself or it is just an artifact from staining. The analysis of poor-quality karyograms, which is a difficulty faced often in preparations from cancer samples, is time consuming and might result in missing the abnormality or difficulty in reporting the exact breakpoint within the chromosome. We developed ChromoEnhancer, a novel artificial-intelligence-based method to enhance neoplastic karyogram images. The method is based on Generative Adversarial Networks (GANs) with a data-centric approach. GANs are known for the conversion of one image domain to another. We used GANs to convert poor-quality karyograms into good-quality images. Our method of karyogram enhancement led to robust routine cytogenetic analysis and, therefore, to accurate detection of cryptic chromosomal abnormalities. To evaluate ChromoEnahancer, we randomly assigned a subset of the enhanced images and their corresponding original (unenhanced) images to two independent cytogeneticists to measure the karyogram quality and the elapsed time to complete the analysis, using four rating criteria, each scaled from 1 to 5. Furthermore, we compared the enhanced images with our method to the original ones, using quantitative measures (PSNR and SSIM metrics).

Nonalcoholic steatohepatitis (NASH) is part of a spectrum of conditions collectively referred to as nonalcoholic fatty liver disease (NAFLD). NASH/NAFLD is the most common chronic liver disease. NASH is defined as ≥5% hepatic steatosis along with hepatocellular injury. Histopathological features that indicate hepatocellular injury in NASH include ballooning degeneration, lobular inflammation, and apoptotic bodies. Scoring schemes, such as the NASH Clinical Research Network (CRN), use those histopathological features to grade the severity of the disease and determine a stage based on the amount of fibrosis. Among the NAFLD spectrum, NASH has the highest risk of developing fibrosis and progressing to liver cirrhosis. Therefore, accurate and timely diagnosis is crucial in order to initiate therapy and prevent disease complications as well as liver-related mortality. Although several imaging modalities and laboratory assays have been introduced to diagnose NASH, a liver biopsy remains the gold standard for diagnosing, grading, and staging the disease.

The DePEC-Nutrition trial is a complex dietary and behavioural intervention of salt intake reduction combined with increased high-nitrate vegetable consumption among Malaysian middle-aged and older adults with elevated blood pressure. This study aimed to assess the feasibility and acceptability of the trial. Participants were recruited from the South East Asia Community Observatory (SEACO) database and randomised into one of four groups: (1) low salt; (2) high-nitrate vegetable; (3) combined high-nitrate vegetable and low salt; and (4) control. The intervention included a combination of group counselling sessions, information booklets, reinforcement videos and text messages to modify dietary behaviour. The primary outcomes evaluated were the measures of feasibility and acceptability of (1) recruitment, follow-up attendance and retention; (2) data collection procedures and clinical outcome measures; and (3) individual and combined multi-modal dietary interventions. A total of 74 participants were recruited, and the 10-month retention rate was 73%. Data collection procedures were acceptable with minimal missing data. All intervention strategies were feasible and acceptable, with group counselling being the most acceptable strategy. This study provides important insights into improving the screening process of participants, facilitating their access to the research facilities and refining the measurement protocols and dietary recommendations, which are instrumental in formulating the design of a full-scale definitive DePEC-Nutrition trial.

Objective We implement 2 different multitask learning (MTL) techniques, hard parameter sharing and cross-stitch, to train a word-level convolutional neural network (CNN) specifically designed for automatic extraction of cancer data from unstructured text in pathology reports. We show the importance of learning related information extraction (IE) tasks leveraging shared representations across the tasks to achieve state-of-the-art performance in classification accuracy and computational efficiency. Materials and Methods Multitask CNN (MTCNN) attempts to tackle document information extraction by learning to extract multiple key cancer characteristics simultaneously. We trained our MTCNN to perform 5 information extraction tasks: (1) primary cancer site (65 classes), (2) laterality (4 classes), (3) behavior (3 classes), (4) histological type (63 classes), and (5) histological grade (5 classes). We evaluated the performance on a corpus of 95 231 pathology documents (71 223 unique tumors) obtained from the Louisiana Tumor Registry. We compared the performance of the MTCNN models against single-task CNN models and 2 traditional machine learning approaches, namely support vector machine (SVM) and random forest classifier (RFC). Results MTCNNs offered superior performance across all 5 tasks in terms of classification accuracy as compared with the other machine learning models. Based on retrospective evaluation, the hard parameter sharing and cross-stitch MTCNN models correctly classified 59.04% and 57.93% of the pathology reports respectively across all 5 tasks. The baseline models achieved 53.68% (CNN), 46.37% (RFC), and 36.75% (SVM). Based on prospective evaluation, the percentages of correctly classified cases across the 5 tasks were 60.11% (hard parameter sharing), 58.13% (cross-stitch), 51.30% (single-task CNN), 42.07% (RFC), and 35.16% (SVM). Moreover, hard parameter sharing MTCNNs outperformed the other models in computational efficiency by using about the same number of trainable parameters as a single-task CNN. Conclusions The hard parameter sharing MTCNN offers superior classification accuracy for automated coding support of pathology documents across a wide range of cancers and multiple information extraction tasks while maintaining similar training and inference time as those of a single task–specific model.

Building a data-driven model to localize the origin of ventricular activation from 12-lead electrocardiograms (ECG) requires addressing the challenge of large anatomical and physiological variations across individuals. The alternative of a patient-specific model is, however, difficult to implement in clinical practice because the training data must be obtained through invasive procedures. In this paper, we present a novel approach that overcomes this problem of the scarcity of clinical data by transferring the knowledge from a large set of patient-specific simulation data while utilizing domain adaptation to address the discrepancy between the simulation and clinical data. The method that we have developed quantifies non-uniformly distributed simulation errors, which are then incorporated into the process of domain adaptation in the context of both classification and regression. This yields a quantitative model that, with the addition of 12-lead ECG data from each patient, provides progressively improved patient-specific localizations of the origin of ventricular activation. We evaluated the performance of the presented method in localizing 75 pacing sites on three in-vivo premature ventricular contraction (PVC) patients. We found that the presented model showed an improvement in localization accuracy relative to a model trained on clinical ECG data alone or a model trained on combined simulation and clinical data without considering domain shift. Furthermore, we demonstrated the ability of the presented model to improve the real-time prediction of the origin of ventricular activation with each added clinical ECG data, progressively guiding the clinician towards the target site.

Protein phosphorylation is a post-translational modification that enables various cellular activities and plays essential roles in protein interactions. Phosphorylation is an important process for the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To shed more light on the effects of phosphorylation, we used an ensemble of neural networks to predict potential kinases that might phosphorylate SARS-CoV-2 nonstructural proteins (nsps) and molecular dynamics (MD) simulations to investigate the effects of phosphorylation on nsps structure, which could be a potential inhibitory target to attenuate viral replication. Eight target candidate sites were found as top-ranked phosphorylation sites of SARS-CoV-2. During the process of molecular dynamics (MD) simulation, the root-mean-square deviation (RMSD) analysis was used to measure conformational changes in each nsps. Root-mean-square fluctuation (RMSF) was employed to measure the fluctuation in each residue of 36 systems considered, allowing us to evaluate the most flexible regions. These analysis shows that there are significant structural deviations in the residues namely nsp1 THR 72, nsp2 THR 73, nsp3 SER 64, nsp4 SER 81, nsp4 SER 455, nsp5 SER284, nsp6 THR 238, and nsp16 SER 132. The identified list of residues suggests how phosphorylation affects SARS-CoV-2 nsps function and stability. This research also suggests that kinase inhibitors could be a possible component for evaluating drug binding studies, which are crucial in therapeutic discovery research.

Glaucoma is the second leading cause of blindness worldwide, and peripapillary atrophy (PPA) is a morphological symptom associated with it. Therefore, it is necessary to clinically detect PPA for glaucoma diagnosis. This study was aimed at developing a detection method for PPA using fundus images with deep learning algorithms to be used by ophthalmologists or optometrists for screening purposes. The model was developed based on localization for the region of interest (ROI) using a mask region-based convolutional neural networks R-CNN and a classification network for the presence of PPA using CNN deep learning algorithms. A total of 2,472 images, obtained from five public sources and one Saudi-based resource (King Abdullah International Medical Research Center in Riyadh, Saudi Arabia), were used to train and test the model. First the images from public sources were analyzed, followed by those from local sources, and finally, images from both sources were analyzed together. In testing the classification model, the area under the curve’s (AUC) scores of 0.83, 0.89, and 0.87 were obtained for the local, public, and combined sets, respectively. The developed model will assist in diagnosing glaucoma in screening programs; however, more research is needed on segmenting the PPA boundaries for more detailed PPA detection, which can be combined with optic disc and cup boundaries to calculate the cup-to-disc ratio.

DPPA4 is essential for the pluripotent stem cell state, yet its function is poorly understood. DPPA4 is localized in the nucleus, where it is associated with active chromatin. We now report that it is also present in the cytosol, where it appears as diffused clouds, distinct foci and sometimes as spaghetti-like structures. This cytosolic localization is dynamic and DPPA4 shuttles between the cytosol and the nucleus. Its presence is almost abolished from the nucleus upon differentiation. Co-immunoprecipitation studies highlighted novel protein interactors, many of which are also found in the cytosol and are implicated in mRNA processing and RNA and protein transport between the cytosol and the nucleus. Finally, the depletion of DPPA4 resulted in cytosolic accumulation of vesicles. The cytosolic presence of DPPA4 highlights unexplored research directions that could significantly advance the understanding of DPPA4 in pluripotent stem cells and in cancer.

Objective To address the opioid overdose epidemic, it is important to understand the broad scope of efforts under way in states, particularly states in which the rate of opioid-involved overdose deaths is declining. The primary objective of this study was to examine core elements of overdose prevention activities in 4 states with a high rate of opioid-involved overdose deaths that experienced a decrease in opioid-involved overdose deaths from 2016 to 2017. Methods We identified 5 states experiencing decreases in age-adjusted mortality rates for opioid-involved overdoses from 2016 to 2017 and examined their overdose prevention programs via program narratives developed with collaborators from each state’s overdose prevention program. These program narratives used 10 predetermined categories to organize activities: legislative policies; strategic planning; data access, capacity, and dissemination; capacity building; public-facing resources (eg, web-based dashboards); training resources; enhancements and improvements to prescription drug monitoring programs; linkage to care; treatment; and community-focused initiatives. Using qualitative thematic analysis techniques, core elements and context-specific activities emerged. Results In the predetermined categories of programmatic activities, we identified the following core elements of overdose prevention and response: comprehensive state policies; strategic planning; local engagement; data access, capacity, and dissemination; training of professional audiences (eg, prescribers); treatment infrastructure; and harm reduction. Conclusions The identification of core elements and context-specific activities underscores the importance of implementation and adaptation of evidence-based prevention strategies, interdisciplinary partnerships, and collaborations to address opioid overdose. Further evaluation of these state programs and other overdose prevention efforts in states where mortality rates for opioid-involved overdoses declined should focus on impact, optimal timing, and combinations of program activities during the life span of an overdose prevention program.

Recently, the sudden outbreak of the COVID-19 virus caused a major health crisis by affecting masses around the world. The virus, which is known to be highly contagious, has forced the research community and governments to fight the disease and take prompt actions by applying various strategies to keep the numbers under control. These strategies range from imposing strict social distancing measures, isolating infected cases, and enforcing either a partial or a full lockdown, to mathematical modeling and contact-tracing applications. In this work, we survey the current contact-tracing apps and organize them based on underlying technologies such as Bluetooth, Wi-Fi, GPS, geofencing, and Quick Response (QR) codes. We compare the main features of 22 existing applications and highlight each of the pros and cons associated with these different technologies.

Since the launch of the Sustainable Development Goals (SDGs) in 2015, Africa has made some progress towards its achievements, particularly in the area of gender equality- SDG 5, climate change -SDG 13 and preserving life on land- SDG 15. Although, some African countries have made tangible impact on the other goals such as health, food production and economic growth; these efforts experienced some setbacks with attention shifting to curbing the spread of the novel coronavirus. As much as mitigating the spread of the spread of COVID-19 is important, so is ensuring efforts made on other goals are not lost, as the SDGs are much interconnected, and failure in one impacts others. For the African continent to achieve sustainable development beyond COVID-19, strategic actions which will involve innovations, evaluations and strong political will towards implementations must be taken by relevant stakeholders, so the continent is not left behind in the global goals achievement by 2030.

ObjectivesTo describe the patterns and outcomes of traumatic spinal injuries (TSIs) in a tertiary care trauma centre in Riyadh, Saudi Arabia.DesignRetrospective medical record review.SettingLevel 1 trauma centre for all patients presented from 1 February 2016 to 31 December 2018.Participants and dataRecords of patients presenting with any spinal trauma were reviewed, and the data obtained included age, gender, nationality (as Saudi and non-Saudi), date of presentation, site of fracture/injury, associated injuries, mechanism of injury, presence of neurological involvement and hospital mortality.Main outcomesFrequencies of different types of TSI across various subgroups.ResultsWe identified 692 patients who presented with TSI throughout the study period. The mean age was 36.9 years. Males represented 83.2% (n=576) of the sample size, and the most common mechanism of injury was motor vehicle collision (MVC), accounting for 66.8% of cases (n=462), while fall-related injuries were seen in 31.6% of cases (n=219). A total of 454 (65.6%) of all patients were Saudi, and 332 (73.1%) of the TSIs in Saudis were due to MVC. Non-Saudi cases accounted for 238 (34.4%) of all patients, and 89 (37.4%) of the non-Saudi injuries were due to falls from height, and this association was statistically significant (pConclusionTSI was not thoroughly examined in Saudi Arabia; therefore, this study is considered the first to be done in the Kingdom using a representative sample. The fact that non-Saudi patients had a higher proportion of falls as a mechanism of injury should be taken into consideration in terms of raising awareness and taking more safety precautions, as most construction workers tend to be expatriates.

Visceral Leishmaniasis (VL) due to Leishmania donovani is a neglected protozoan parasitic disease in humans, which is usually fatal if untreated. Phlebotomus orientalis, the predominant VL vector in East Africa, is a highly exophilic/exophagic species that poses a major challenge to current Integrated Vector Management (IVM). Here we report results of pilot studies conducted in rural villages in Gedarif state, Sudan, to evaluate outdoor residual spraying of 20mg active ingredient (a.i.) /m2 deltamethrin insecticide applied to the characteristic household compound boundary reed fence and to the outside of household buildings (Outdoor Residual Insecticide Spraying, ODRS), and as an alternative, spraying restricted to the boundary fence only (Restricted Outdoor Residual Insecticide Spraying, RODRS). Four to six clusters of 20 households were assigned to insecticide treatments or control in three experiments. Changes in sand fly numbers were monitored over 2,033 trap-nights over 43–76 days follow-up in four sentinel houses per cluster relative to unsprayed control clusters. Sand fly numbers were monitored by sticky traps placed on the ground on the inside (“outdoor”) and the outside (“peridomestic”) of the boundary fence, and by CDC light traps suspended outdoors in the household compound. The effects of ODRS on sand fly numbers inside sleeping huts were monitored by insecticide knockdown. After a single application, ODRS reduced P. orientalis abundance by 83%-99% in outdoor and peridomestic trap locations. ODRS also reduced numbers of P. orientalis found resting inside sleeping huts. RODRS reduced outdoor and peridomestic P. orientalis by 60%-88%. By direct comparison, RODRS was 58%-100% as effective as ODRS depending on the trapping method. These impacts were immediate on intervention and persisted during follow-up, representing a large fraction of the P. orientalis activity season. Relative costs of ODRS and RODRS delivery were $5.76 and $3.48 per household, respectively. The study demonstrates the feasibility and high entomological efficacy of ODRS and RODRS, and the expected low costs relative to current IVM practises. These methods represent novel sand fly vector control tools against predominantly exophilic/exophagic sand fly vectors, aimed to lower VL burdens in Sudan, with potential application in other endemic regions in East Africa., Author summary Phlebotomus orientalis is the predominant vector of visceral leishmaniasis (VL, kala azar) in Sudan and other countries of East Africa, where the disease causes high morbidity and mortality. This sylvatic sand fly species is abundant in wild habitats characterized by presence of black cotton soil and vegetation dominated by Balanites aegyptiaca and/or Acacia seyal trees. In villages, the vector bites people in the household yard and in nearby peri-domestic locations, exhibiting limited indoor resting behaviour. The marked exophagic and exophilic behaviours of P. orientalis represent a profound challenge for VL control by excluding indoor residual spraying of insecticides (IRS) and compromising the efficacy of insecticide-impregnated bednets (ITNs). In this study, we evaluated the entomological efficacy of residual pyrethroid applied outdoors to household boundary fences and the exterior walls of household huts (outdoor residual insecticide spraying, ODRS), to reduce the abundance of P. orientalis inside and outside houses. We also evaluated the entomological impact of a restricted outdoor residual insecticide spraying (RODRS), whereby insecticide was applied only to the boundary fence. The study was carried out in June 2016-June 2017 in Jebel-Algana and Umsalala villages, Gedarif state, eastern Sudan, which are highly endemic for VL. The results showed that a single ODRS application of 20mg a.i. /m2 2.8% deltamethrin provided average reductions of 83%-99% in outdoor and peridomestic P. orientalis sand fly numbers relative to unsprayed control clusters. RODRS reduced outdoor and peridomestic P. orientalis by 60%-88%. The average cost of ODRS and RODRS per household were $5.76 and $3.48, respectively. The costs of these community-based control measures were substantially lower than the costs of LLINs, which is the only evidence-based tool used to protect against VL in the area. Future studies should evaluate the impact of ODRS/RODRS transmission of VL incidence in endemic villages and in seasonal agricultural farms.

IntroductionGlobal population ageing is one of the key factors linked to the projected rise of dementia incidence. Hence, there is a clear need to identify strategies to overcome this expected health burden and have a meaningful impact on populations’ health worldwide. Current evidence supports the role of modifiable dietary and lifestyle risk factors in reducing the risk of dementia. In South-East Asia, changes in eating and lifestyle patterns under the influence of westernised habits have resulted in significant increases in the prevalence of metabolic, cardiovascular and neurodegenerative non-communicable diseases (NCDs). Low vegetable consumption and high sodium intake have been identified as key contributors to the increased prevalence of NCDs in these countries. Therefore, nutritional and lifestyle strategies targeting these dietary risk factors are warranted. The overall objective of this randomised feasibility trial is to demonstrate the acceptability of a dietary intervention to increase the consumption of high-nitrate green leafy vegetables and reduce salt intake over 6 months among Malaysian adults with raised blood pressure.Methods and analysisPrimary outcomes focus on feasibility measures of recruitment, retention, implementation and acceptability of the intervention. Secondary outcomes will include blood pressure, cognitive function, body composition and physical function (including muscle strength and gait speed). Adherence to the dietary intervention will be assessed through collection of biological samples, 24-hour recall and Food Frequency Questionnaire. A subgroup of participants will also complete postintervention focus groups to further explore the feasibility considerations of executing a larger trial, the ability of these individuals to make dietary changes and the barriers and facilitators associated with implementing these changes.Ethics and disseminationEthical approval has been obtained from Monash University Human Research Ethics Committee and Medical Research and Ethics Committee of Malaysia. Results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences.ISRCTN47562685; Pre-results.

OBJECTIVES: Chronic hepatitis B virus infection is a major cause of morbidity and mortality. The aim of the study is to describe the hepatic histology in children chronically infected with hepatitis B virus living in the United States and Canada. METHODS: Liver biopsies of 134 treatment-naïve children with chronic hepatitis B virus infection were scored for inflammation, fibrosis, and other histological features, and correlated with clinical and laboratory data. RESULTS: Sixty percentage of subjects acquired the infection vertically, 51% were male, and 69% were hepatitis B e antigen-positive at the time of the biopsy. Hepatitis B DNA levels were generally high (mean 7.70 log IU/mL), as was serum alanine aminotransferase (median 120 U/L). Using the Ishak-modified histology activity index scoring system, interface hepatitis was mild in 31%, moderate in 61%, and severe in 6%. Lobular inflammation was mild in 54%, moderate in 29%, and marked in 7%. Portal inflammation was mild in 38% and moderate in 62% of subjects. Eighteen percentage had no fibrosis, 59% had portal expansion without bridging fibrosis, 19% had bridging fibrosis, and 4% had cirrhosis. Alanine aminotransferase positively correlated with inflammation and fibrosis. Neither age, duration of infection, nor Hepatitis B virus DNA levels correlated with fibrosis. Fibrosis-4 index did not correlate with fibrosis but correlated with inflammation. Aspartate aminotransferase/platelet ratio index correlated with both inflammation and fibrosis. CONCLUSIONS: Chronic hepatitis B virus infection results in significant inflammation and fibrosis during childhood. Serum alanine aminotransferase is a strong indicator of the severity and extent of hepatic inflammation and fibrosis.

BackgroundPublished training recommendations exist for youth athletes aimed at reducing injury risk. No studies have assessed the impact of counselling interventions using training recommendations on risk of injury in young athletes.ObjectivesTo determine if online training counselling regarding safe sport participation can reduce injury risk in youth athletes and to assess recommendation compliance, including barriers to compliance.MethodsA multicentre randomised intervention trial was performed at two Midwestern academic institutions with expertise in treating young athletes. Enrolled subjects ages 8–17 completed a baseline risk assessment survey and were randomised to a control or intervention group. Both groups completed exposure surveys every 3 months for 1 year. The intervention group also received online training counselling on safe sport participation every 3 months. Training characteristics including training volume, degree of specialisation and adherence to recommendations were captured. Differences in self-reported injury between groups, compliance to recommendations and barriers to compliance were evaluated.ResultsAt baseline, n=357 subjects were enrolled (n=172 control and n=185 intervention). Controls were nearly twice as likely to be injured during the intervention period after controlling for age, sex, baseline injury and level of specialisation. No improvement in recommendation compliance was detected among intervention subjects. Primary barriers to compliance were no prior knowledge of recommendations, personal choice and following coaches’ recommendations.ConclusionsIn this convenience sample of youth athletes, electronic training counselling surrounding safe sports participation was not determined to affect injury risk. Lack of knowledge and adherence to appropriate training recommendations is evident and barriers to compliance exist.

Background Human decidua basalis mesenchymal stem/multipotent stromal cells (DBMSCs) inhibit endothelial cell activation by inflammation induced by monocytes. This property makes them a promising candidate for cell-based therapy to treat inflammatory diseases, such as atherosclerosis. This study was performed to examine the ability of DBMSCs to protect endothelial cell functions from the damaging effects resulting from exposure to oxidatively stress environment induced by H2O2 and monocytes. Methods DBMSCs were co-cultured with endothelial cells isolated from human umbilical cord veins in the presence of H2O2 and monocytes, and various functions of endothelial cell were then determined. The effect of DBMSCs on monocyte adhesion to endothelial cells in the presence of H2O2 was also examined. In addition, the effect of DBMSCs on HUVEC gene expression under the influence of H2O2 was also determined. Results DBMSCs reversed the effect of H2O2 on endothelial cell functions. In addition, DBMSCs reduced monocyte adhesion to endothelial cells and also reduced the stimulatory effect of monocytes on endothelial cell proliferation in the presence of H2O2. Moreover, DBMSCs modified the expression of many genes mediating important endothelial cell functions. Finally, DBMSCs increased the activities of glutathione and thioredoxin reductases in H2O2-treated endothelial cells. Conclusions We conclude that DBMSCs have potential for therapeutic application in inflammatory diseases, such as atherosclerosis by protecting endothelial cells from oxidative stress damage. However, more studies are needed to elucidate this further.

BACKGROUND: Exposure to stressful working conditions without adequate stress-coping strategies may lead to stress and even psychiatric morbidity. There are a dearth of studies on stress-coping strategies among consultant physicians in the Arabian Gulf. OBJECTIVES: Determine stress-coping strategies among consultants in Saudi Arabia and the relationship of strategies to level of stress. DESIGN: Analytical cross-sectional study. SETTINGS: Conducted between November 2014 and March 2015 among physician consultants registered at the Saudi Commission for Health Specialties. SUBJECTS AND METHODS: Text messages were used to directly ask consultants to complete an online questionnaire. MAIN OUTCOME MEASURES: The 28-item Brief COPE inventory and the Perceived Stress Scale. SAMPLE SIZE: 582. RESULTS: The consultants were largely males (71%) and Saudi (56%), and their mean age was 46.9 (7.9) years. Adaptive stress-coping strategies were more frequently used than maladaptive stress-coping strategies (68% versus 49%). Stress levels were positively correlated with maladaptive stress-coping strategies (r=0.41, P

Kidney involvement with COVID-19 infection is a well-known complication, and the majority of kidney involvement is related to ischemic injury/acute tubular injury. However, there are some cases of glomerulonephritis, the etiology of which is not yet known, but an immune process is likely to be the trigger.A 27-year-old man presented to our hospital with facial puffiness and lower-limb swelling.Laboratory assessment revealed features of impaired kidney function with proteinuria and hematuria; COVID-19 polymerase chain reaction was positive, which was consistent with pauci-immune crescentic focal segmental glomerulonephritis.After renal biopsy, the patient was started on methylprednisolone and rituximab. Due to worsening kidney parameters, he underwent intermittent hemodialysis as needed.Kidney function tests partially improved; he was discharged on oral steroids with follow-up in the nephrology clinic to observe for the need for further hemodialysis.We conducted a literature review of cases of glomerulonephritis associated with COVID-19 and described numerous types of glomerulonephritis. This report highlights the importance of recognizing emerging glomerulonephritis with COVID-19, the different pathological patterns of renal biopsies, and management interventions and responses.

Antibiotic resistance (AR) is a growing public health concern worldwide, and it is a top health challenge in the 21st century. AR among Enterobacteriaceae is rapidly increasing, especially in third-generation cephalosporins and carbapenems. Further, strains carrying mobilized colistin resistance ( mcr) genes 1 and 2 have been isolated from humans, food-producing animals, and the environment. The uncontrolled use of antibiotics in food-producing animals is a major factor in the generation and spread of AR. No studies have been done to evaluate AR in the veterinary sector of Qatar. This study aimed at establishing primary baseline data for the prevalence of AR among food-producing animals in Qatar. Fecal samples (172) were obtained from two broiler farms and one live bird market in Qatar, and 90 commensal Escherichia coli bacteria were isolated and subjected to susceptibility testing against 16 clinically relevant antibiotics by using the E-test method. The results found that 81 (90%) of 90 isolates were resistant to at least one antibiotic, 14 (15.5%) of 90 isolates were colistin resistant, 2 (2.2%) of 90 isolates were extended-spectrum β-lactamase producers, and 2 (2.2%) of 90 isolates were multidrug resistant to four antibiotic classes. Extended-spectrum β-lactamase-producing E. coli and colistin-resistant isolates were confirmed by using double-disc susceptibility testing and PCR, respectively. Such a high prevalence of antibiotic-resistant E. coli could be the result of a long application of antibiotic treatment, and it is an indicator of the antibiotic load in food-producing animals in Qatar. Pathogens carrying AR can be easily transmitted to humans through consumption of undercooked food or noncompliance with hygiene practices, mandating prompt development and implementation of a stewardship program to control and monitor the use of antibiotics in the community and agriculture.

Background Rhazya stricta Decne. is a medicinal plant that is widespread in Saudi Arabia and desert areas of the Arabian Peninsula. Its extract contains alkaloids, tannins, and flavonoids that are involved in different biological activities. The study aim was to evaluate the effects of Rhazya stricta plant extracts on the proliferation and differentiation of NTERA-2 (NT2) pluripotent embryonal carcinoma cells. Methods Soxhlet extraction was carried out using different solvents to extract stems, leaves and fruit parts of this plant. Cytotoxicity was evaluated by an MTS cell viability assay. The ability of the plant extract to induce cell differentiation was examined phenotypically using an inverted light microscope. The expression of pluripotency markers was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry. Phytochemical screening of chloroform stem extracts was carried out and a chromatographic fingerprint was generated using gas chromatography – mass spectrometry (GC-MS). Results Chloroform stem extract induced differentiation of NT2 cells at 5 μg/ml, and the differentiated cells exhibited neurite formation. Following induction of differentiation, there was significant down-regulation of the pluripotency marker genes Oct4 and Sox2. In addition, the surface antigen pluripotency marker, TRA-1-60, was strongly down-regulated. Phytochemical analysis of the extract showed the presence of alkaloids and saponins. The chromatogram revealed the presence of fifteen compounds with different retention times. Conclusion Our results demonstrate for the first time that chloroform stem extract of R. stricta can induce neuronal differentiation of stem cells at an early stage and may contain potential therapeutic agent that can be used in neurodegenerative diseases.

Background:Political unrest in the Middle East heightens the possibility of catastrophe due to violent conflict and/or terrorist attacks. However, the disaster risk reduction strategy in the Saudi health care system appears to be a reactive approach focused more on flood hazards than other threats. Given the current unstable political situation in its neighboring countries and Saudi Arabia’s key role in providing humanitarian assistance and disaster relief to those affected by internal conflicts and wars, it is essential to develop a framework for training standards related to complex humanitarian disasters to provide the requisite skills and knowledge in a gradual manner, according to local context and international standards. This framework could also support the World Health Organization’s (WHO; Geneva, Switzerland) initiative for establishing a national disaster assistance team in Saudi Arabia.Problem:The main aim of this study is to provide Saudi health care providers with a competencies-based course in Basic Principles of Complex Humanitarian Emergency.Methods:The interactive, competencies-based course in Basic Principles of Complex Humanitarian Emergency was designed by five experts in disaster medicine and humanitarian relief in three stages, accordance to international standards and the local context. The course was piloted over five days at the Officers Club of the Ministry of Interior (MOI; Riyadh, Saudi Arabia). The 33 participants were from different health disciplines of the government sectors in-country. The participants completed the pre- and post-tests and attended three pilot workshops for disaster community awareness.Results:The overall knowledge scores were significantly higher in the post-test (62.9%) than the pre-test (44.2%). There were no significant differences in the pre- and post-knowledge scores for health care providers from the different government health disciplines. A 10-month, post-event survey demonstrated that participants were satisfied with their knowledge retention. Importantly, three of them (16.6%) had the opportunity to put this knowledge into practice in relation to humanitarian aid response.Conclusion:Delivering a competencies-based course in Basic Principles of Complex Humanitarian Emergency for health care providers can help improve their knowledge and skills for humanitarian assistance and disaster relief, which is crucial for disaster preparedness augmentation in Saudi Arabia.

We introduce a deep learning architecture, hierarchical self-attention networks (HiSANs), designed for classifying pathology reports and show how its unique architecture leads to a new state-of-the-art in accuracy, faster training, and clear interpretability. We evaluate performance on a corpus of 374,899 pathology reports obtained from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program. Each pathology report is associated with five clinical classification tasks – site, laterality, behavior, histology, and grade. We compare the performance of the HiSAN against other machine learning and deep learning approaches commonly used on medical text data – Naive Bayes, logistic regression, convolutional neural networks, and hierarchical attention networks (the previous state-of-the-art). We show that HiSANs are superior to other machine learning and deep learning text classifiers in both accuracy and macro F-score across all five classification tasks. Compared to the previous state-of-the-art, hierarchical attention networks, HiSANs not only are an order of magnitude faster to train, but also achieve about 1% better relative accuracy and 5% better relative macro F-score.

Background & Aims Clearance of hepatitis B surface antigen (HBsAg) from serum is the most desirable end point and a proposed definition of functional cure for hepatitis B virus (HBV) infection. However, little is known about the long-term durability of HBsAg loss, and there is controversy over whether the development of antibodies against HBsAg (anti-HBs) is required for maintenance. We aimed to assess the durability of spontaneous or treatment-related (interferon or nucleos(t)ide analogue [NA]) loss of HBsAg. Methods We performed a retrospective study of patients with chronic HBV infection followed up at the National Institutes of Health from February 1980 through November 2017. We identified those with HBsAg loss, confirmed on 2 visits at least 24 weeks apart. Patients with hepatitis C virus, hepatitis D virus, human immunodeficiency virus, or human T lymphocyte virus co-infection or HBsAg loss after liver transplantation were excluded. Patients were assigned to the following groups: spontaneous clearance (cleared HBsAg without ever receiving treatment or those who received treatment with a NA or interferon and discontinued therapy >5 years before HBsAg loss), interferon-treated (cleared HBsAg either during treatment or ≤5 years after stopping interferon), and NA-treated (cleared HBsAg either during treatment or ≤5 years after stopping NA). Results Among the 787 HBsAg-positive patients, 89 achieved HBsAg loss; 65 of 89 had confirmed HBsAg loss, which was spontaneous in 19 of the patients (29%), after interferon in 22 (34%), and after NA in 24 (37%). Of the 65 patients with confirmed loss of HBsAg, 62 patients (95%) remained HBsAg negative after a mean time of 9.6 years from the first negative HBsAg test result. HBsAg seroreversion occurred in 3 of the 46 treated patients (7%) (1 interferon and 2 NA), 1 of whom was positive for anti-HBs. At the time of HBsAg loss, 33 of 65 (51%) were anti-HBs positive. At the last follow-up evaluation, anti-HBs was detectable in 50 of the 62 patients (81%) assessed. The rate of development of anti-HBs was proportionally higher among interferon-treated patients (19 of 21; 90%) than NA-treated patients (17 of 22; 77%) or patients with spontaneous loss of HBsAg (14 of 19; 74%). Conclusions In a retrospective study of 787 HBsAg-positive patients, loss of HBsAg (either spontaneous or after treatment) was confirmed in 8% and was durable. Seroconversion to anti-HBs increased over time and appeared to be more frequent after interferon treatment. HBsAg loss is therefore a robust end point for functional cure.

To explore potential gender differences in the factors associated with asthma-specific quality of life (AQL).A cross-sectional study of consecutive series of adult patients attending primary care centers at three major hospitals in Riyadh, Saudi Arabia, was performed. AQL was measured using a standardized version of the AQL questionnaire (min = 1, max = 7), with higher scores indicating a better AQL. Multiple linear regression analysis was performed.The mean AQL was 4.3 (standard deviation [SD] = 1.5) for males and 4.0 (SD = 1.3) for females (p = 0.113). With each unit increase in asthma control, the AQL improved by 0.19 points (95% confidence interval [CI] = 0.14-0.23) in men and by 0.21 points (95% CI = 0.16-0.25) in women. Daily tobacco smoking was associated with a 0.72 point (95% CI = 0.14-1.30) decrease in the AQL among males. Women who had a household member who smoked inside the house had a significantly lower AQL (B = -0.59, 95% CI = -1.0 - -0.19). A monthly household income of 25,000 Saudi Riyals or more was associated with a better AQL among men (B = 0.51, 95% CI = 0.01-1.01), whereas being employed exhibited a protective effect in women (B = 0.48, 95% CI = 0.11-0.84). Higher levels of perceived asthma severity were associated with better AQL in women (B = 0.82, 95% CI = 0.36-1.28).Our findings revealed gender-specific differences in the correlates of AQL in Saudi Arabia, particularly in tobacco exposure, socio-economic factors and perceived asthma severity.

Objective: In machine learning, it is evident that the classification of the task performance increases if bootstrap aggregation (bagging) is applied. However, the bagging of deep neural networks takes tremendous amounts of computational resources and training time. The research question that we aimed to answer in this research is whether we could achieve higher task performance scores and accelerate the training by dividing a problem into sub-problems. Materials and Methods : The data used in this study consist of free text from electronic cancer pathology reports. We applied bagging and partitioned data training using Multi-Task Convolutional Neural Network (MT-CNN) and Multi-Task Hierarchical Convolutional Attention Network (MT-HCAN) classifiers. We split a big problem into 20 sub-problems, resampled the training cases 2,000 times, and trained the deep learning model for each bootstrap sample and each sub-problem—thus, generating up to 40,000 models. We performed the training of many models concurrently in a high-performance computing environment at Oak Ridge National Laboratory (ORNL). Results: We demonstrated that aggregation of the models improves task performance compared with the single-model approach, which is consistent with other research studies; and we demonstrated that the two proposed partitioned bagging methods achieved higher classification accuracy scores on four tasks. Notably, the improvements were significant for the extraction of cancer histology data, which had more than 500 class labels in the task; these results show that data partition may alleviate the complexity of the task. On the contrary, the methods did not achieve superior scores for the tasks of site and subsite classification. Intrinsically, since data partitioning was based on the primary cancer site, the accuracy depended on the determination of the partitions, which needs further investigation and improvement. Conclusion: Results in this research demonstrate that 1. The data partitioning and bagging strategy achieved higher performance scores. 2. We achieved faster training leveraged by the high-performance Summit supercomputer at ORNL.

Individual electronic health records (EHRs) and clinical reports are often part of a larger sequence-for example, a single patient may generate multiple reports over the trajectory of a disease. In applications such as cancer pathology reports, it is necessary not only to extract information from individual reports, but also to capture aggregate information regarding the entire cancer case based off case-level context from all reports in the sequence. In this paper, we introduce a simple modular add-on for capturing case-level context that is designed to be compatible with most existing deep learning architectures for text classification on individual reports. We test our approach on a corpus of 431,433 cancer pathology reports, and we show that incorporating case-level context significantly boosts classification accuracy across six classification tasks-site, subsite, laterality, histology, behavior, and grade. We expect that with minimal modifications, our add-on can be applied towards a wide range of other clinical text-based tasks.

The objective of our study was to determine levels of endothelial progenitor cells (EPCs) in preeclampsia and normotensive pregnant women.Prospective cohort study of women with preeclampsia and normotensive pregnancies. EPCs were estimated by flow cytometry. Multiple linear regression was used to assess the association of EPCs with preeclampsia adjusting for maternal age, body mass index (BMI), gestation and ethnicity.Levels of EPCs in preeclampsia and normotensive pregnancies, with CD-34 and vascular endothelial (VE)-cadherin as markers of EPCs. VE-cadherin is an endothelial cell adhesion molecule used to delineate endothelial lineage of EPCs.There were thirty women in the preeclampsia group and thirty-three in the normotensive group. The two groups were similar except for the BMI and blood pressures, which were higher in preeclampsia. On multiple linear regression, EPCs numbers were significantly higher by 29 (95% confidence interval 11.7-46.6, p = 0.001) in preeclampsia compared to the normotensive group. There was significant positive correlation between EPCs and systolic blood pressure in preeclampsia (Spearman correlation coefficient 0.39, p = 0.03).Although widely used in cardiovascular disease other than preeclampsia, this is the first study using VE-cadherin as a marker of endothelial lineage to define EPCs in preeclampsia. Our results suggest the higher number of EPCs in preeclampsia may be a response of the bone marrow to endothelial injury.

9 p., Background: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. Methods: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. Findings: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p

Background Human decidua parietalis mesenchymal stem/multipotent stromal cells (DPMSCs) have unique phenotypic and functional properties that make them promising candidates for cell-based therapy. Here, we investigated DPMSC interaction with natural killer (NK) cells, and the effects of this interaction on NK cell phenotypic characteristics and functional activities. Methods DPMSCs isolated from the decidua parietalis of human fetal membranes were cultured with interleukin (IL)-2-activated and IL-2-unactivated NK cells isolated from healthy human peripheral blood. NK cell proliferation and cytolytic activities were then examined using functional assays. NK cell expression of receptors mediating the cytolytic activity against DPMSCs, and the mechanism underlying this effect on DPMSCs, were also examined using flow cytometry and light microscopy, respectively. Results DPMSCs stimulated IL-2-induced proliferation of resting NK cells and the proliferation of activated NK cells. Moreover, IL-2-activated NK cells, but not freshly isolated NK cells, efficiently lysed DPMSCs. The induction of this NK cell cytolytic activity against DPMSCs was mediated by the activating NK cell receptors NKG2D, CD69, NKp30, and NKp44. However, DPMSCs showed a direct induction of NK cell cytolytic activity through CD69. We also found that DPMSCs expressed the ligands for these activating NK cell receptors including Nectin-2, ULBP-2, MICA, and MICB. Although DPMSCs expressed HLA class I molecules, they were susceptible to lysis by NK cells, suggesting that HLA class I antigens do not play a significant role in NK cell cytolytic action. In addition, DPMSCs did not inhibit NK cell cytolytic activity against cancer cells. Importantly, DPMSCs significantly increased NK expression of inflammatory molecules with anticancer activities. Conclusions We conclude that DPMSCs have potential for therapeutic application in cancer therapy, but not in transplantation or immunological diseases.

To improve outcomes for people with substance dependence and HIV infection or at risk for HIV infection, patients were enrolled in a primary care-based addiction treatment program from 2008–2012 that included a comprehensive substance use assessment, individual and group counseling, addiction pharmacotherapy and case management. We examined whether predisposing characteristics (depression, housing status, polysubstance use) and an enabling resource (buprenorphine treatment) were associated with engagement in the program and persistent substance dependence at 6 months. At program enrollment 61% were HIV-infected, 53% reported heroin use, 46% reported alcohol use, 37% reported cocaine use, and 28% reported marijuana use in the past 30 days, 72% reported depression, 19% were homeless, and 53% had polysubstance use. Within 6-months 60% had been treated with buprenorphine. Engagement (defined as 2 visits in first 14 days and 2 additional visits in next 30 days) occurred in 64%; 49% had substance dependence at 6-months. Receipt of buprenorphine treatment was associated with engagement (Adjusted Odds Ratio (AOR) 8.32 95% CI: 4.13–16.77). Self-reported depression at baseline was associated with substance dependence at 6-months (AOR 3.30 95% CI: 1.65–6.61). Neither housing status nor polysubstance use was associated with engagement or substance dependence. The FAST PATH program successfully engaged and treated patients in a primary care-based addiction treatment program. Buprenorphine, a partial opioid agonist, was a major driver of addiction treatment engagement. Given depression's association with adverse outcomes in this clinical population, including mental health treatment as part of integrated care holds potential to improve addiction treatment outcomes.

Background Long intervals between patient visits and limited time with patients can result in clinical inertia and suboptimal achievement of treatment goals. These obstacles can be improved with a multidisciplinary care program. The present study aimed to assess the impact of such a program on glycemic control and cardiovascular risk factors. Methods In a randomized, parallel-group trial, we assigned 263 patients with poorly controlled type 2 diabetes mellitus (T2DM) to either a control group, standard care program, or a multidisciplinary care program involving a senior family physician, clinical pharmacy specialist, dietician, diabetic educator, health educator, and social worker. The participants were followed for a median of 10 months, between September 2013 and September 2014. Glycated hemoglobin (HbA1c), fasting blood glucose (FBG), lipid profiles, and blood pressure (BP) were measured. The assignment was blinded for the assessors of the study outcomes. The study registry number is. Results In the intervention group, there were statistically significant (p

BACKGROUND. Monogenic IFN–mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease. METHODS. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes–associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. RESULTS. Eighteen patients were treated for a mean duration of 3.0 years (1.5–4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93–1.78) to 0.25 (IQR, 0.1–0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31–1.09) to 0.11 mg/kg/day (IQR, 0.02–0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients’ quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. CONCLUSION. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment. TRIAL REGISTRATION. ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01724580","term_id":"NCT01724580"}}NCT01724580 and {"type":"clinical-trial","attrs":{"text":"NCT02974595","term_id":"NCT02974595"}}NCT02974595. FUNDING. This research was supported by the Intramural Research Program of the NIH, NIAID, and NIAMS. Baricitinib was provided by Eli Lilly and Company, which is the sponsor of the expanded access program for this drug.

Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the endothelium to undergo a change to a proinflammatory and procoagulant state (ie, endothelial cell activation). An initial response to endothelial cell activation is monocyte adhesion. Activation typically involves increased proliferation and enhanced expression of adhesion and inflammatory markers by endothelial cells. Sustained endothelial cell activation leads to a type of damage to the body associated with inflammatory diseases, such as atherosclerosis. In this study, we examined the ability of DBMSCs to protect endothelial cells from activation through monocyte adhesion, by modulating endothelial proliferation, migration, adhesion, and inflammatory marker expression. Endothelial cells were cocultured with DBMSCs, monocytes, monocyte-pretreated with DBMSCs and DBMSC-pretreated with monocytes were also evaluated. Monocyte adhesion to endothelial cells was examined following treatment with DBMSCs. Expression of endothelial cell adhesion and inflammatory markers was also analyzed. The interaction between DBMSCs and monocytes reduced endothelial cell proliferation and monocyte adhesion to endothelial cells. In contrast, endothelial cell migration increased in response to DBMSCs and monocytes. Endothelial cell expression of adhesion and inflammatory molecules was reduced by DBMSCs and DBMSC-pretreated with monocytes. The mechanism of reduced endothelial proliferation involved enhanced phosphorylation of the tumor suppressor protein p53. Our study shows for the first time that DBMSCs protect endothelial cells from activation by inflammation triggered by monocyte adhesion and increased endothelial cell proliferation. These events are manifest in inflammatory diseases, such as atherosclerosis. Therefore, our results suggest that DBMSCs could be usefully employed as a therapeutic strategy for atherosclerosis.

Persistent left superior vena cava (PLSVC) is a common cardiac anomaly associated with congenital heart diseases. A diagnosis of PLSVC usually warrants a detailed fetal echocardiography. Lesser known associations are the extra cardiac anomalies notably the upper airway and the gastrointestinal tract anomalies. We highlight here the importance of detailed fetal assessment for extra cardiac anomalies in addition to fetal echocardiography in fetuses diagnosed with PLSVC. We hereby present a preterm infant who presented with a triad of PLSVC, laryngeal atresia, and esophageal atresia.

Endoscopic placement of enteral self-expandable metallic stents is an alternative to surgical gastrojejunostomy (GJ) for palliation of malignant gastric outlet obstruction (GOO). Factors associated with clinical outcomes are not known. The aims of this study are to compare the overall complication rate and effectiveness (duration of oral intake) between endoscopic stenting (ES) and GJ in patients with GOO and identify predictors of clinical outcomes.This was a retrospective cohort study at a single tertiary academic center. Patients who underwent ES or GJ for treatment of GOO between 1/2001 and 12/2010 were identified using an institutional claims database. The electronic medical records for each patient were reviewed. Univariate and multivariate logistic regression analyses were performed to study the association of treatment outcomes with patient factors and cancer therapy.120 patients had ES while 227 had GJ. Technical success was higher for GJ (99 vs. 96 %, p = 0.004). Complication rates were higher in the GJ group (22.10 vs. 11.66 %, p = 0.02). Reintervention was more common with ES [adjusted odds ratio (OR) 9.18, p0.0001]. Mean length of hospital stay (LOHS) was shorter (adjusted p = 0.005) in the ES compared with the GJ group. However, mean hospital charges, including reinterventions, were greater in the ES group (US $34,250 vs. US $27,599, p = 0.03). ES and GJ had comparable reintervention-free time in patients who had reintervention (88 vs. 106 days, respectively, p = 0.79). Chemotherapy [adjusted hazard ratio (HR) 30.57, p = 0.04] and radiation therapy (adjusted HR 0.35, p = 0.03) were associated with significantly longer duration of oral intake after ES or GJ.ES is associated with fewer complications, shorter LOHS, but higher reintervention rates and overall charges.

Background : Locally advanced rectal cancer can be down staged by neoadjuvant therapy and the resultant tumor response can be quantified histologically. This study aimed to assess pathological response of neoadjuvant chemoradiation in patients with locally advanced rectal cancers treated in Wad Medani Teaching Hospital (WMTH) and National Cancer Institute (NCI), Wad Medani, Sudan. Patients and methods : A total of 36 consecutive patients with locally advanced rectal cancer that were managed in WMTH and NCI during the period from 2006-2011 were reviewed. Preoperative pelvic radiotherapy was delivered. Total of 46 Gray were delivered concurrently with 5- fluorouracil (5-FU) on the first and last week of radiation. Total mesorectal excision of the rectal tumour either by anterior or abdominoperineal resections was planned at 6-8 weeks from completion of preoperative treatment. The pathological response to therapy was assessed by histopathology examination of the surgical specimen. Results : Initial clinical staging of patients revealed 58.3% of them were stage T3/T4N2M0 and 41.7% were stage T3N0M0. Down-staging to stage T1/T2N0M0 was found in 36.1% and stage T3N0M0 in 30.6%. No response was seen in 8.3% of cases with stage T3/T4N2M0 while complete clinical response (no residual) was seen in 25.0%. Complete histological response was observed in 13.8%. Positive lymph-nodes metastasis was confirmed in 8.3% of cases. Conclusion : Neoadjuvant chemoradiation is a reasonable option for cases of rectal cancer and deserves further evaluation. Keywords : Neoadjuvant, rectal cancer, chemoradiation, pathological response.