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Background and Purpose: Understanding the relationship of COVID-19 to stroke is important. We compare characteristics of pre-pandemic historical stroke (Pre-C), cases in acute COVID infection (Active-C) and in patients who have recovered from COVID-19 infection (Post-C)., Methods: We interrogated the Qatar stroke database for all stroke admissions between Jan 2019 and Feb 2020 (Pre-C) to Active-C (Feb2020-Feb2021) and Post-C to determine how COVID-19 affected ischemic stroke sub-types, clinical course, and outcomes prior to, during and post-pandemic peak. We used the modified Rankin Scale (mRS) to measure outcome at 90-days (mRS 0-2 good recovery and mRS 3-6 as poor recovery). For the current analysis, we compared the clinical features and prognosis in patients with confirmed acute ischemic stroke., Results: There were 1413 cases admitted (pre-pandemic: 1324, stroke in COVID-19: 46 and recovered COVID-19 stroke: 43). Patients with Active-C were significantly younger, had more severe symptoms, fever on presentation, more ICU admissions and poor stroke recovery at discharge when compared to Pre-C and Post-C. Large vessel disease and cardioembolic disease was significantly more frequent in Active-C compared to PRE-C or post-C., Conclusions: Stroke in Post-C has characteristics similar to Pre-C with no evidence of lasting effects of the virus on the short-term. However, Active-C is a more serious disease and tends to be more severe and have a poor prognosis., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Pial collateral blood flow is a major determinant of the outcomes of acute ischemic stroke. This study was undertaken to determine whether retinal vessel metrics can predict the pial collateral status and stroke outcomes in patients., Methods: Thirty-five patients with acute stroke secondary to middle cerebral artery (MCA) occlusion underwent grading of their pial collateral status from computed tomography angiography and retinal vessel analysis from retinal fundus images., Results: The NIHSS (14.7 ± 5.5 vs 10.1 ± 5.8, p = 0.026) and mRS (2.9 ± 1.6 vs 1.9 ± 1.3, p = 0.048) scores were higher at admission in patients with poor compared to good pial collaterals. Retinal vessel multifractals: D0 (1.673±0.028vs1.652±0.025, p = 0.028), D1 (1.609±0.027vs1.590±0.025, p = 0.044) and f(α)max (1.674±0.027vs1.652±0.024, p = 0.019) were higher in patients with poor compared to good pial collaterals. Furthermore, support vector machine learning achieved a fair sensitivity (0.743) and specificity (0.707) for differentiating patients with poor from good pial collaterals. Age (p = 0.702), BMI (p = 0.422), total cholesterol (p = 0.842), triglycerides (p = 0.673), LDL (p = 0.952), HDL (p = 0.366), systolic blood pressure (p = 0.727), HbA1c (p = 0.261) and standard retinal metrics including CRAE (p = 0.084), CRVE (p = 0.946), AVR (p = 0.148), tortuosity index (p = 0.790), monofractal Df (p = 0.576), lacunarity (p = 0.531), curve asymmetry (p = 0.679) and singularity length (p = 0.937) did not differ between patients with poor compared to good pial collaterals., Conclusions: This is the first translational study to show increased retinal vessel multifractal dimensions in patients with acute ischemic stroke and poor pial collaterals. A retinal vessel classifier was developed to differentiate between patients with poor and good pial collaterals and may allow rapid non-invasive identification of patients with poor pial collaterals., Competing Interests: The authors have declared that no competing interests exist.

Background: Several reports document a decrease in the rates of stroke hospital admissions during the covid-19 pandemic. There is very little information whether the admission rates will change as the infection is controlled. We report on our rates of admissions before, during and following the peak of covid-19 infections in a prospective database from Qatar., Methods and Results: The stroke admissions in the six months prior to COVID-19 pandemic averaged 229/month. There was a decrease to 157/month in March-June during the peak of the pandemic. In the 6 months following the peak, as covid-19 numbers began to decrease, the average numbers increased back to 192/month. There was an increase in severe ischemic strokes and decreased in functional recovery. The decreased admissions were mainly driven by fewer stroke mimics. Patients presenting with ischemic stroke or cerebral hemorrhage remained unchanged., Conclusions: Fewer stroke mimics presenting to the hospital can explain the fewer admissions and poor outcome at the height of the covid-19 pandemic. The continued decrease in the number of ischemic stroke and stroke mimic admissions following the pandemic peak requires more study., Competing Interests: The authors have declared that no competing interests exist.

There is an urgent need for an accurate antibody test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have developed 3 ELISA methods, trimer spike IgA, trimer spike IgG, and nucleocapsid IgG, for detecting anti-SARS-CoV-2 antibodies. We evaluated their performance along with four commercial ELISAs, EDI™ Novel Coronavirus COVID-19 ELISA IgG and IgM, Euroimmun Anti-SARS-CoV-2 ELISA IgG and IgA, and one lateral flow assay, DPP® COVID-19 IgM/IgG System (Chembio). Both sensitivity and specificity were evaluated and the probable causes of false-positive reactions were determined. The assays were evaluated using 300 pre-epidemic samples and 100 PCR-confirmed COVID-19 samples. The sensitivities and specificities of the assays were as follows: 90%/100% (in-house trimer spike IgA), 90%/99.3% (in-house trimer spike IgG), 89%/98.3% (in-house nucleocapsid IgG), 73.7%/100% (EDI nucleocapsid IgM), 84.5%/95.1% (EDI nucleocapsid IgG), 95%/93.7% (Euroimmun S1 IgA), 82.8%/99.7% (Euroimmun S1 IgG), 82.0%/91.7% (Chembio nucleocapsid IgM), 92%/93.3% (Chembio nucleocapsid IgG). The presumed causes of false positive results from pre-epidemic samples in commercial and in-house assays were mixed. In some cases, assays lacked reproducibility. In other cases, reactivity was abrogated by competitive inhibition (spiking the sample with the same antigen that was used for coating ELISAs prior to performing the assay), suggesting positive reaction could be attributed to the presence of antibodies against these antigens. In other cases, reactivity was consistently detected but not abrogated by the spiking, suggesting positive reaction was not attributed to the presence of antibodies against these antigens. Overall, there was wide variability in assay performance using our samples, with in-house tests exhibiting the highest combined sensitivity and specificity. The causes of "false positivity" in pre-epidemic samples may be due to plasma antibodies apparently reacting with the corresponding antigen, or spurious reactivity may be directed against non-specific components in the assay system. Identification of these targets will be essential to improving assay performance., Competing Interests: The authors have declared that no competing interests exist.

Background: Studies assessing the burden of stroke in Qataris are limited. We aim to study stroke in the Qatari population., Methods: A retrospective review was undertaken of all Qatari adults presenting with stroke to Hamad Medical Corporation over a 5-year period. Descriptive statistics were used to summarize demographic and all other clinical characteristics of the patients. The primary outcome was the incidence of stroke in the Qatari patients. Comparison was made between the sexes., Results: 862 patients were included, with 58.9% being male. The average incidence of stroke over the 5-year period was 92.04 per 100,000 adult Qatari population. The mean age of the cohort was 64.3±14.4 years, (range 19-105 years). The mean age of first ever cerebrovascular event was 63.2±14.5 years. The diagnosis was ischemic stroke in (73.7%), transient ischemic attack in (13.8%), intracerebral hemorrhage (ICH) in (11.6%), subarachnoid hemorrhage in (0.7%) and (0.2%) cerebral venous sinus thrombosis. Small vessel disease was the most common cause of ischemic stroke accounting for (46.5%), followed by large artery atherosclerosis (24.5%). Hypertension (82.7%) and diabetes (71.6%) were particularly prevalent in this cohort. Females were older (65.8±14.1 vs 63.4±14.5 years), had more hypertension and diabetes and more disability or death at 90 days (p<0.05) compared to Qatari males., Conclusion: Stroke occurs at a significantly lower age in Qataris compared to the western population. This study has uncovered sex differences that need to be studied further., Competing Interests: The authors have declared that no competing interests exist.

The Ikzf1 locus encodes the lymphoid specific transcription factor Ikaros, which plays an essential role in both T and B cell differentiation, while deregulation or mutation of IKZF1/Ikzf1 is involved in leukemia. Tissue-specific and cell identity genes are usually associated with clusters of enhancers, also called super-enhancers, which are believed to ensure proper regulation of gene expression throughout cell development and differentiation. Several potential regulatory regions have been identified in close proximity of Ikzf1, however, the full extent of the regulatory landscape of the Ikzf1 locus is not yet established. In this study, we combined epigenomics and transcription factor binding along with high-throughput enhancer assay and 4C-seq to prioritize an enhancer element located 120 kb upstream of the Ikzf1 gene. We found that deletion of the E120 enhancer resulted in a significant reduction of Ikzf1 mRNA. However, the epigenetic landscape and 3D topology of the locus were only slightly affected, highlighting the complexity of the regulatory landscape regulating the Ikzf1 locus., Competing Interests: The authors have declared that no competing interests exist

Understanding key healthcare system challenges experienced by women during pregnancy and birth is crucial to scale up available interventions and reduce perinatal mortality. A community perspective about preferences and experience of care during this period can be used to improve community-based programs to reduce perinatal mortality. Using a qualitative exploratory approach, we examined women's experience of perinatal loss, aiming to understand the main factors, as perceived and experienced by women, leading to perinatal loss. Qualitative in-depth Interviews were conducted with 25 mothers with a recent perinatal loss, three family members, six healthcare officials, and two focus group discussions with 17 lady health workers. Data were analysed using inductive and deductive coding, by thematic analysis. Our findings revealed three distinct but interrelated themes, which include: 1) poor access to care during pregnancy and birth, 2) unavailability of appropriate healthcare services, and 3) poor quality of care during pregnancy and birth. Women frequently delayed seeking formal care around birth because of delays by themselves, their family members, or the local traditional birth attendants who frequently induced births at women's homes without recognising the dangers to the mothers or their babies. Preference for private care was common, however they often could not bear the cost of care when they needed caesarean section or in-patient care for their sick newborns because these services were absent in public health facilities of the district. Referral to the regional tertiary care hospital was often not officially arranged leading to risky births in small and crowded private clinics. Women's views about negative staff attitudes and the lack of attention given to them in public health facilities highlighted a lack of quality and respectful antenatal care. Improvement in women's access to essential care during pregnancy and around birth, availability of emergency obstetric and newborn care, improving the quality of maternal and newborn care in both public and private health facilities at the district level might reduce perinatal mortality in Pakistan., Competing Interests: The authors have declared that no competing interests exist.

Background and Purpose: Patients with acute stroke and mild or rapidly improving symptoms frequently show progression. The role of reperfusion treatment in such patients is not clear. We hypothesized that progression was most likely in patients with cortical localization and such patients may benefit from thrombolysis., Material and Methods: We interrogated Hamad Stroke Database to evaluate 90-days outcome in patients with acute ischemic stroke admitted within 4 hours and a NIHSS score of ≤6. Evaluation was based on localization (lacunar or cortical), multi-model imaging abnormalities and whether they received rt-PA. The 90-day mRS was used to determine outcome., Results: During study period 6381 patients were admitted with acute stroke. Mild stroke within 4 hours was diagnosed in 506 [no thrombolysis: 381(lacunar: 213; cortical: 168), thrombolysis: 125 (lacunar: 45; cortical: 80)]. The rt-PA treated patients had significantly higher NIHSS (2.94±3.9 versus 1.28±2.46, p<0.0001), increased rates of complications (16.0% versus 3.9%, p<0.0001) and longer hospital stay (6.05±8.1 versus 3.78±3.6 days; p<0.001). In patients with cortical stroke, intracranial arterial occlusions (11.6% vs 3.9%, p<0.0001) and CTP mismatch (22.2% vs 4.4%, p<0.0001) were more frequent in rt-PA treated patients. Discharge mRS (33.6% versus 13.9%, p<0.001) and 90-days mRS (23.2% versus 11.8%, p = 0.002) was significantly worse in patients with cortical stroke (rt-PA-treated and untreated patients)., Conclusions: The outcome in patients with mild stroke depends on lesion location (lacunar versus cortical) and severity of symptoms. Patients who receive rt-PA have significantly larger deficits, increased imaging abnormalities and higher rates of hospital complication, explaining the poor outcome in such subjects., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Corneal nerve damage may be a surrogate marker for the risk of ischemic stroke. This study was undertaken to determine if there is greater corneal nerve damage in patients with recurrent ischemic stroke., Methods: Corneal confocal microscopy (CCM) was used to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) and corneal nerve fiber tortuosity (CNFT) in 31 patients with recurrent ischemic stroke, 165 patients with a first acute ischemic stroke and 23 healthy control subjects., Results: Triglycerides (P = 0.004, P = 0.017), systolic BP (P = 0.000, P = 0.000), diastolic BP (P = 0.000, P = 0.000) and HbA1c (P = 0.000, P = 0.000) were significantly higher in patients with first and recurrent stroke compared to controls. There was no difference in age, BMI, HbA1c, total cholesterol, triglycerides, LDL, HDL, systolic and diastolic BP between patients with a first and recurrent ischemic stroke. However, CNFD was significantly lower (24.98±7.31 vs 29.07±7.58 vs 37.91±7.13, P<0.05) and CNFT was significantly higher (0.085±0.042 vs 0.064±0.037 vs 0.039±0.022, P<0.05) in patients with recurrent stroke compared to first stroke and healthy controls. CNBD (42.21±24.65 vs 50.46±27.68 vs 87.24±45.85, P<0.001) and CNFL (15.66±5.70, P<0.001 vs 17.38±5.06, P = 0.003) were equally reduced in patients with first and recurrent stroke compared to controls (22.72±5.14)., Conclusions: Corneal confocal microscopy identified greater corneal nerve fibre loss in patients with recurrent stroke compared to patients with first stroke, despite comparable risk factors. Longitudinal studies are required to determine the prognostic utility of corneal nerve fiber loss in identifying patients at risk of recurrent ischemic stroke., Competing Interests: The authors have declared that no competing interests exist.

Due to higher temperatures and lower water availability, climate change is likely to have a major impact on walnut production in the near future. Climate change will alter the land suitability for walnut cultivation around the world, especially in arid and semi-arid regions like Iran. Here, land suitability for the cultivation of walnut (Juglans regia L.) in Iran was determined using the GIS for present and future conditions (2020-2049) with an approach to climate change. Accordingly, data from 375 synoptic stations throughout Iran were gathered for climatic factors including average, minimum and maximum temperatures, relative humidity and chilling requirement. Also, ASTER sensors (Advanced Spaceborne Thermal Emission and Reflection Radiometer) and their data provided this research with cells that make a precision of 150 m (5 s), and the data were used for gauging geological parameters such as altitude and land slope. The electrical conductivity (EC) of soil and water were informed by the data bank of the Iranian Water Resources Management. The results of temperature simulations for the future (2020-2049) were analyzed by 21 AOGCM-AR5 models under the RCP4.5 emission scenario. In the first phase of evaluations, the maps of land suitability were constructed for present conditions by considering a network of the above-mentioned parameters. By combining these layers of information, the final map of land suitability was illustrated for walnut cultivation. In the second phase, the NEX-GDDP was used in order to determine land suitability for the future (2020-2049). The results showed that Iran currently has 582844 km2 of land suitable for walnut cultivation. However, the future will see less suitable lands: the current area will be reduced by 6.19%, from 582844 km2 to 546710 km2. In general, the northern, northwestern and western margins of Iran are currently suitable for walnut cultivation. By approximation, these lands will also be major areas for prospective cultivations of walnut in the future (2020-2049), even though their current stretch will be reduced., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine if corneal confocal microscopy can identify corneal nerve and endothelial cell abnormalities and may be useful in the prognostication of patients with transient ischemic attack [1] or minor ischemic stroke (IS)., Methods: Thirty-six patients admitted with TIA (n = 14) or minor IS (n = 22) underwent transcranial Doppler evaluation and corneal confocal microscopy and were compared with 18 healthy controls., Results: Corneal nerve fiber density (P = 0.002), branch density (P = 0.004) and fiber length (P = 0.004) were significantly lower in patients with TIA or minor IS compared to controls, with no difference between patients with TIA and minor IS. Endothelial cell density (P = 0.003) was lower and endothelial cell area (P = 0.003) and perimeter (P = 0.006) were significantly higher in patients with TIA or minor IS compared to controls, with no difference between patients with TIA and minor IS. There were no differences in corneal nerve or endothelial cell morphology between patients with and without abnormal cerebrovascular reactivity. HbA1c was independently associated with CNFL, and endothelial cell polymegathism and pleomorphism were associated with both HbA1c and total cholesterol., Conclusion: Corneal confocal microscopy identifies corneal nerve fiber loss and endothelial cell abnormalities in patients with TIA and minor IS and independent associations with HbA1c and cholesterol., Competing Interests: The authors have declared that no competing interests exist.

The recent development in the technology has increased the complexity of image contents and demand for image classification becomes more imperative. Digital images play a vital role in many applied domains such as remote sensing, scene analysis, medical care, textile industry and crime investigation. Feature extraction and image representation is considered as an important step in scene analysis as it affects the image classification performance. Automatic classification of images is an open research problem for image analysis and pattern recognition applications. The Bag-of-Features (BoF) model is commonly used to solve image classification, object recognition and other computer vision-based problems. In BoF model, the final feature vector representation of an image contains no information about the co-occurrence of features in the 2D image space. This is considered as a limitation, as the spatial arrangement among visual words in image space contains the information that is beneficial for image representation and learning of classification model. To deal with this, researchers have proposed different image representations. Among these, the division of image-space into different geometric sub-regions for the extraction of histogram for BoF model is considered as a notable contribution for the extraction of spatial clues. Keeping this in view, we aim to explore a Hybrid Geometric Spatial Image Representation (HGSIR) that is based on the combination of histograms computed over the rectangular, triangular and circular regions of the image. Five standard image datasets are used to evaluate the performance of the proposed research. The quantitative analysis demonstrates that the proposed research outperforms the state-of-art research in terms of classification accuracy., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To determine the prevalence and severity of neuropathic pain, sudomotor dysfunction and abnormal vibration perception in patients with MS., Methods: 73 patients with MS and 32 age-matched healthy controls underwent assessment of expanded disability severity score (EDSS), DN4 to assess neuropathic pain, electrochemical skin conductance (ESC) to assess sudomotor function and vibration perception threshold (VPT)., Results: Patients with MS had a higher DN4 score (p < 0.001) with 14% fulfilling the criteria for neuropathic pain elevated VPT (p < 0.001) and lower ESC on the feet (p < 0.001) and hands (p < 0.001) compared to control participants. ESC on the feet (32% of MS patients) and hands (30% of MS patients) were lower, and DN4 (77% of MS patients) and VPT (64% of MS patients) were greater than 2SD of the healthy control values, respectively. EDSS correlated with the number of relapses (r = 0.564, p < 0.001), VPT (r = -0.457, < 0.001) and ESC on the feet (r = -0.268, p = 0.023)., Conclusions: Patients with multiple sclerosis have evidence of sudomotor dysfunction and elevated vibration perception, which were associated with neurological disability from MS.

Background: It is evident that professional driving is associated with substantial changes in lifestyle habits. Professional drivers are prone to metabolic syndrome (MetS) and its complications because their working environment is characterized by numerous stress factors such as lack of physical activity due to working in a fixed position, disruption in diet, and irregular sleep habits. The aim of the present study was to estimate the prevalence of MetS among long distance drivers residing in West Azerbaijan province in Iran., Materials: To assess the prevalence of metabolic syndrome among professional long distance drivers, 12138 participants were enrolled in this cross sectional study. The MetS was defined using International Diabetes Federation criteria., Results: Among 12138 participants, 3697 subjects found to be MetS. The crude and age-adjusted rates of MetS were 30.5% and 32.4% respectively. Based on Body mass index (BMI), 5027 subjects (41.4%) were overweight (BMI ≥ 25.01-30 kg/m2), and 2592 (21.3%) were obese (BMI ≥ 30.01 kg/m2). The presence of central obesity was more common than other components. The associations of MetS with BMI, pack-year smoking, age, weekly driving duration and driving experiences were significant in the logistic regression. By increasing BMI, pack-year smoking, age, weekly driving duration and driving experiences, odds ratio of MetS was increased., Conclusion: The study suggests that MetS has become a noteworthy health problem among Iranian long distance drivers. This might be due to the following facts: sitting in a fixed position for long hours while working, cigarette smoking, job stress, unhealthy diet and lack of physical activity. Educational programs should be established for promoting healthy lifestyle and also for early detection and appropriate interventions.

Background: The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address "food-abuse" disorders. We demonstrate a molecular link between impairment of a central kinase (Akt) involved in insulin signaling induced by exposure to a high-fat (HF) diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA) rich brain structures, such as striatum, provide motivation stimuli for feeding. In these central circuitries, DA dysfunction is posited to contribute to obesity pathogenesis. We identified a mechanistic link between metabolic dysregulation and the maladaptive behaviors that potentiate weight gain. Insulin, a hormone in the periphery, also acts centrally to regulate both homeostatic and reward-based HF feeding. It regulates DA homeostasis, in part, by controlling a key element in DA clearance, the DA transporter (DAT). Upon HF feeding, nigro-striatal neurons rapidly develop insulin signaling deficiencies, causing increased HF calorie intake., Methodology/principal Findings: We show that consumption of fat-rich food impairs striatal activation of the insulin-activated signaling kinase, Akt. HF-induced Akt impairment, in turn, reduces DAT cell surface expression and function, thereby decreasing DA homeostasis and amphetamine (AMPH)-induced DA efflux. In addition, HF-mediated dysregulation of Akt signaling impairs DA-related behaviors such as (AMPH)-induced locomotion and increased caloric intake. We restored nigro-striatal Akt phosphorylation using recombinant viral vector expression technology. We observed a rescue of DAT expression in HF fed rats, which was associated with a return of locomotor responses to AMPH and normalization of HF diet-induced hyperphagia., Conclusions/significance: Acquired disruption of brain insulin action may confer risk for and/or underlie "food-abuse" disorders and the recalcitrance of obesity. This molecular model, thus, explains how even short-term exposure to "the fast food lifestyle" creates a cycle of disordered eating that cements pathological changes in DA signaling leading to weight gain and obesity.