Search

Ben Li,1– 4,* Farah Shaikh,2,* Abdelrahman Zamzam,2 Ravel Raphael,2 Muzammil H Syed,2 Houssam K Younes,5 Rawand Abdin,6 Mohammad Qadura1– 3,7 1Department of Surgery, University of Toronto, Toronto, Ontario, Canada; 2Division of Vascular Surgery, St. Michael’s Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada; 3Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; 4Temerty Centre for Artificial Intelligence Research and Education in Medicine (T-CAIREM), University of Toronto, Toronto, Ontario, Canada; 5Heart, Vascular, & Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates; 6Department of Medicine, McMaster University, Hamilton, Ontario, Canada; 7Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada*These authors contributed equally to this workCorrespondence: Mohammad Qadura, University of Toronto, Division of Vascular Surgery, St. Michael’s Hospital, Unity Health Toronto, 30 Bond Street, Suite 7-076, Toronto, Ontario, M5B 1W8, Canada, Tel +1 416-864-5154, Email mohammad.qadura@utoronto.caPurpose: Inflammatory biomarkers associated with peripheral artery disease (PAD) have been examined separately; however, an algorithm that includes a panel of inflammatory proteins to inform prognosis of PAD could improve predictive accuracy. We developed predictive models for 2-year PAD-related major adverse limb events (MALE) using clinical/inflammatory biomarker data.Methods: We conducted a prognostic study using 2 phases (discovery/validation models). The discovery cohort included 100 PAD patients that were propensity-score matched to 100 non-PAD patients. The validation cohort included 365 patients with PAD and 144 patients without PAD (non-matched). Plasma concentrations of 29 inflammatory proteins were determined at recruitment and the cohorts were followed for 2 years. The outcome of interest was 2-year MALE (composite of major amputation, vascular intervention, or acute limb ischemia). A random forest model was trained with 10-fold cross-validation to predict 2-year MALE using the following input features: 1) clinical characteristics, 2) inflammatory biomarkers that were expressed differentially in PAD vs non-PAD patients, and 3) clinical characteristics and inflammatory biomarkers.Results: The model discovery cohort was well-matched on age, sex, and comorbidities. Of the 29 proteins tested, 5 were elevated in PAD vs non-PAD patients (MMP-7, MMP-10, IL-6, CCL2/MCP-1, and TFPI). For prognosis of 2-year MALE on the validation cohort, our model achieved AUROC 0.63 using clinical features alone and adding inflammatory biomarker levels improved performance to AUROC 0.84.Conclusion: Using clinical characteristics and inflammatory biomarker data, we developed an accurate predictive model for PAD prognosis.Plain Language Summary: Inflammatory biomarkers associated with peripheral artery disease (PAD) have been examined separately; however, an algorithm that includes an inflammatory protein panel to inform prognosis of PAD may improve predictive accuracy. We developed predictive models for 2-year major adverse limb events (MALE) using clinical characteristics (demographics, comorbidities, and medications) and a panel of 5 PAD-specific inflammatory biomarkers (MMP-7, MMP-10, IL-6, CCL2/MCP-1, and TFPI) that achieved excellent performance on an independent validation cohort (AUROC 0.84). The models developed through this study may support PAD risk-stratification and targeted management strategies.Keywords: inflammatory biomarkers, predictive model, prognosis, peripheral artery disease

Umamah bint Khalid,1 Muddasar Naeem,2 Fabrizio Stasolla,2 Madiha Haider Syed,1,3 Musarat Abbas,1 Antonio Coronato2 1Department of Electronics, Quaid-I-Azam University, Islamabad, 44000, Pakistan; 2Research Center on ICT Technologies for Healthcare and Wellbeing, Università Telematica “Giustino Fortunato”, Benevento, 82100, Italy; 3Institute of Information Technology, Quaid-i-Azam University, Islamabad, 44000, PakistanCorrespondence: Muddasar Naeem, Email m.naeem@unifortunato.euAbstract: Rehabilitation is an important and necessary part of local and global healthcare services along with treatment and palliative care, prevention of disease, and promotion of good health. The rehabilitation process helps older and young adults even children to become as independent as possible in activities of daily life and enables participation in useful living activities, recreation, work, and education. The technology of Artificial Intelligence (AI) has evolved significantly in recent years. Many activities related to rehabilitation have been getting benefits from using AI techniques. The objective of this review study is to explore the advantages of AI for rehabilitation and how AI is impacting the rehabilitation process. This study aims at the most critical aspects of the rehabilitation process that could potentially take advantage of AI techniques including personalized rehabilitation apps, rehabilitation through assistance, rehabilitation for neurological disorders, rehabilitation for developmental disorders, virtual reality rehabilitation, rehabilitation of neurodegenerative diseases and Telerehabilitation of Cardiovascular. We presented a survey on the newest empirical studies available in the literature including the AI-based technology helpful in the Rehabilitation process. The novelty feature included but was not limited to an overview of the technological solutions useful in rehabilitation. Seven different categories were identified. Illustrative examples of practical applications were detailed. Implications of the findings for both research and practice were critically discussed. Most of the AI applications in these rehabilitation types are in their infancy and continue to grow while exploring new opportunities. Therefore, we investigate the role of AI technology in rehabilitation processes. In addition, we do statistical analysis of the selected studies to highlight the significance of this review work. In the end, we also present a discussion on some challenges, and future research directions.Keywords: artificial intelligence, machine learning, rehabilitation, healthcare, cognitive skills, cognitive rehabilitation

Complex behaviors arise from neural circuits that assemble from diverse cell types. Sleep is a conserved behavior essential for survival, yet little is known about how the nervous system generates neuron types of a sleep-wake circuit. Here, we focus on the specification of Drosophila 23E10-labeled dorsal fan-shaped body (dFB) long-field tangential input neurons that project to the dorsal layers of the fan-shaped body neuropil in the central complex. We use lineage analysis and genetic birth dating to identify two bilateral type II neural stem cells (NSCs) that generate 23E10 dFB neurons. We show that adult 23E10 dFB neurons express ecdysone-induced protein 93 (E93) and that loss of ecdysone signaling or E93 in type II NSCs results in their misspecification. Finally, we show that E93 knockdown in type II NSCs impairs adult sleep behavior. Our results provide insight into how extrinsic hormonal signaling acts on NSCs to generate the neuronal diversity required for adult sleep behavior. These findings suggest that some adult sleep disorders might derive from defects in stem cell-specific temporal neurodevelopmental programs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: In Sindh Province, Pakistan, confirmed Crimean-Congo haemorrhagic fever (CCHF) increased from zero in 2008 to 16 in 2015-2016. To counter this increase, in 2016, we initiated structured CCHF surveillance to improve estimates of risk factors for CCHF in Sindh and to identify potential interventions., Methods: Beginning in 2016, all referral hospitals in Sindh reported all CCHF cases to surveillance agents. We used laboratory-confirmed cases from CCHF surveillance from 2016 to 2020 to compute incidence rates and in a case-control study to quantify risk factors for CCHF., Results: For the 5 years, CCHF incidence was 4.2 per million for the Sindh capital, Karachi, (68 cases) and 0.4 per million elsewhere. Each year, the onset of new cases peaked during the 13 days during and after the 3-day Eid-al-Adha festival, when Muslims sacrificed livestock, accounting for 38% of cases. In Karachi, livestock for Eid were purchased at a seasonal livestock market that concentrated up to 700,000 livestock. CCHF cases were most common (44%) among the general population that had visited livestock markets (odds ratio = 102)., Conclusions: Urban CCHF in Sindh province is associated with the general public's exposure to livestock markets in addition to high-risk occupations., Competing Interests: Declarations of Competing Interest The authors of the manuscript entitled ‘Risk factors of Crimean-Congo haemorrhagic fever in Sindh Province, Pakistan’ have no competing interests to declare., (Published by Elsevier Ltd.)

Objective: Prognostic tools for individuals with peripheral artery disease (PAD) remain limited. We developed prediction models for 3-year PAD-related major adverse limb events (MALE) using demographic, clinical, and biomarker data previously validated by our group., Methods: We performed a prognostic study using a prospectively recruited cohort of patients with PAD (n = 569). Demographic/clinical data were recorded including sex, age, comorbidities, previous procedures, and medications. Plasma concentrations of three biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], fatty acid binding protein 3 [FABP3], and FABP4) were measured at baseline. The cohort was followed for 3 years. MALE was the primary outcome (composite of open/endovascular vascular intervention or major amputation). We trained three machine learning models with 10-fold cross-validation using demographic, clinical, and biomarker data (random forest, decision trees, and Extreme Gradient Boosting [XGBoost]) to predict 3-year MALE in patients. Area under the receiver operating characteristic curve (AUROC) was the primary model evaluation metric., Results: Three-year MALE was observed in 162 patients (29%). XGBoost was the top-performing predictive model for 3-year MALE, achieving the following performance metrics: AUROC = 0.88 (95% confidence interval [CI], 0.84-0.94); sensitivity, 88%; specificity, 84%; positive predictive value, 83%; and negative predictive value, 91% on test set data. On an independent validation cohort of patients with PAD, XGBoost attained an AUROC of 0.87 (95% CI, 0.82-0.90). The 10 most important predictors of 3-year MALE consisted of: (1) FABP3; (2) FABP4; (3) age; (4) NT-proBNP; (5) active smoking; (6) diabetes; (7) hypertension; (8) dyslipidemia; (9) coronary artery disease; and (10) sex., Conclusions: We built robust machine learning algorithms that accurately predict 3-year MALE in patients with PAD using demographic, clinical, and novel biomarker data. Our algorithms can support risk stratification of patients with PAD for additional vascular evaluation and early aggressive medical management, thereby improving outcomes. Further validation of our models for clinical implementation is warranted., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background/Objectives: Myokines have been demonstrated to be associated with cardiovascular diseases; however, they have not been studied as biomarkers for peripheral artery disease (PAD). We identified interleukin-7 (IL-7) as a prognostic biomarker for PAD from a panel of myokines and developed predictive models for 2-year major adverse limb events (MALEs) using clinical features and plasma IL-7 levels. Methods: A prognostic study was conducted with a cohort of 476 patients (312 with PAD and 164 without PAD) that were recruited prospectively. Their plasma concentrations of five circulating myokines were measured at recruitment, and the patients were followed for two years. The outcome of interest was two-year MALEs (composite of major amputation, vascular intervention, or acute limb ischemia). Cox proportional hazards analysis was performed to identify IL-7 as the only myokine that was associated with 2-year MALEs. The data were randomly divided into training (70%) and test sets (30%). A random forest model was trained using clinical characteristics (demographics, comorbidities, and medications) and plasma IL-7 levels with 10-fold cross-validation. The primary model evaluation metric was the F1 score. The prognostic model was used to classify patients into low vs. high risk of developing adverse limb events based on the Youden Index. Freedom from MALEs over 2 years was compared between the risk-stratified groups using Cox proportional hazards analysis. Results: Two-year MALEs occurred in 28 (9%) of patients with PAD. IL-7 was the only myokine that was statistically significantly correlated with two-year MALE (HR 1.56 [95% CI 1.12-1.88], p = 0.007). For the prognosis of 2-year MALEs, our model achieved an F1 score of 0.829 using plasma IL-7 levels in combination with clinical features. Patients classified as high-risk by the predictive model were significantly more likely to develop MALEs over a 2-year period (HR 1.66 [95% CI 1.22-1.98], p = 0.006). Conclusions: From a panel of myokines, IL-7 was identified as a prognostic biomarker for PAD. Using a combination of clinical characteristics and plasma IL-7 levels, we propose an accurate predictive model for 2-year MALEs in patients with PAD. Our model may support PAD risk stratification, guiding clinical decisions on additional vascular evaluation, specialist referrals, and medical/surgical management, thereby improving outcomes.

Background: Community pharmacists play an important role in increasing vaccination rates especially in countries where they offer vaccination services and administration. However, little is known about community pharmacist's willingness to provide vaccination services in Saudi Arabia. The objective of this study was to assess knowledge, attitudes, willingness and beliefs of community pharmacists in Saudi Arabia towards providing vaccines at pharmacies., Methods: A cross-sectional, online questionnaire-based study using convenience sampling (Snowball technique) was used to obtain responses from community pharmacists across Saudi Arabia. The survey collected information on participants' demographics, knowledge about vaccine, attitude towards vaccine and their attitude to be immunization providers. Bivariate analysis and multiple linear regression models were employed to assess the relationships between demographic variables and outcomes., Results: The study sample consisted of 384 community pharmacists. More than half of participants had poor knowledge about vaccines (54%). Only 8.4% of participants had good knowledge about vaccines. The results indicated that community pharmacists in the study sample have positive attitude toward vaccines and are willing to provide vaccination services. There was a significant relationship between knowledge about vaccine and attitude toward vaccines. Pharmacists with poor knowledge about vaccines had negative attitude toward vaccines as compared to those with high knowledge (β = -1.743; P-value = 0.024). Additionally, there was a significant relationship between knowledge about vaccine and attitude to be immunization providers. Pharmacists with poor knowledge about vaccines had negative attitude to be immunization providers as compared to those with high knowledge (β = -2.631; P-value = 0.002). Furthermore, a significant number of the community pharmacists reported facing critical barriers to provide vaccines including legal liability, lack of personal resources and lack of appropriate training., Conclusion: Comprehensive training and certification programs for pharmacists are crucial to improve their competencies in handling and administering vaccines to increase the rate of vaccinations in Saudi Arabia., Competing Interests: No authors have competing interests, (Copyright: © 2024 Meraya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Complex behaviors are mediated by a diverse class of neurons and glia produced during development. Both neural stem cell-intrinsic and -extrinsic temporal cues regulate the appropriate number, molecular identity, and circuit assembly of neurons. The Drosophila central complex (CX) is a higher-order brain structure regulating various behaviors, including sensory-motor integration, celestial navigation, and sleep. Most neurons and glia in the adult CX are formed during larval development by 16 Type II neural stem cells (NSCs). Unlike Type I NSCs, which directly give rise to the ganglion mother cells (GMCs), Type II NSCs give rise to multiple intermediate neural progenitors (INPs), and each INP in turn generates multiple GMCs, hence fostering the generation of longer and more diverse lineages. This makes Type II NSCs a suitable model to unravel the molecular mechanisms regulating neural diversity in more complex lineages. In this review, we elaborate on the classification and identification of NSCs based on the types of division adopted and the molecular markers expressed in each type. In the end, we discuss genetic methods for lineage analysis and birthdating. We also explain the temporal expression of stem cell factors and genetic techniques to study how stem cell factors may regulate neural fate specification., (© 2024 Cold Spring Harbor Laboratory Press.)

From insects to humans, the nervous system generates complex behaviors mediated by distinct neural circuits that are composed of diverse cell types. During development, the spatiotemporal gene expression of the neural progenitors expands the diversity of neuronal and glial subtypes. Various neural stem cell-intrinsic and -extrinsic gene programs have been identified that are thought to play a major role in generating diverse neuronal and glial cell types. Drosophila has served as an excellent model system for discovering the fundamental principles of nervous system development and function. The sophisticated genetic tools allow us to link the origin and birth timing (the time when a particular neuron is born during development) of neuron types to unique neural stem cells (NSCs) and to a developmental time. In Drosophila , a special class of NSCs called Type II NSCs has adopted a more advanced division mode to generate lineages for the higher-order brain center, the central complex, which is an evolutionarily conserved brain region found in all insects. Type II NSCs, similar to the human outer radial glia, generate intermediate neural progenitors (INPs), which divide many times to produce about eight to 10 progeny. Both Type II NSCs and INPs express distinct transcription factors and RNA-binding proteins that have been proposed to regulate the specification of cell types populating the adult central complex. Here, we describe the recently invented lineage filtering system, called cell class-lineage intersection (CLIn), which enables the tracking and birthdating of the Type II NSC lineages. Using CLIn, one can easily generate clones of different Type II NSCs and identify not only the origins of neurons of interest but also their birth time., (© 2024 Cold Spring Harbor Laboratory Press.)

Complex behaviors depend on the precise developmental specification of neuronal circuits, but the relationship between genetic programs for neural development, circuit structure, and behavioral output is often unclear. The central complex (CX) is a conserved sensory-motor integration center in insects, which governs many higher-order behaviors and largely derives from a small number of type II neural stem cells (NSCs). Here, we show that Imp, a conserved IGF-II mRNA-binding protein expressed in type II NSCs, plays a role in specifying essential components of CX olfactory navigation circuitry. We show the following: (1) that multiple components of olfactory navigation circuitry arise from type II NSCs. (2) Manipulating Imp expression in type II NSCs alters the number and morphology of many of these circuit elements, with the most potent effects on neurons targeting the ventral layers of the fan-shaped body (FB). (3) Imp regulates the specification of Tachykinin-expressing ventral FB input neurons. (4) Imp is required in type II NSCs for establishing proper morphology of the CX neuropil structures. (5) Loss of Imp in type II NSCs abolishes upwind orientation to attractive odor while leaving locomotion and odor-evoked regulation of movement intact. Taken together, our findings establish that a temporally expressed gene can regulate the expression of a complex behavior by developmentally regulating the specification of multiple circuit components and provides a first step toward a developmental dissection of the CX and its roles in behavior., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Peripheral artery disease (PAD) biomarkers have been studied in isolation; however, an algorithm that considers a protein panel to inform PAD prognosis may improve predictive accuracy. Biomarker-based prediction models were developed and evaluated using a model development (n = 270) and prospective validation cohort (n = 277). Plasma concentrations of 37 proteins were measured at baseline and the patients were followed for 2 years. The primary outcome was 2-year major adverse limb event (MALE; composite of vascular intervention or major amputation). Of the 37 proteins tested, 6 were differentially expressed in patients with vs. without PAD (ADAMTS13, ICAM-1, ANGPTL3, Alpha 1-microglobulin, GDF15, and endostatin). Using 10-fold cross-validation, we developed a random forest machine learning model that accurately predicts 2-year MALE in a prospective validation cohort of PAD patients using a 6-protein panel (AUROC 0.84). This algorithm can support PAD risk stratification, informing clinical decisions on further vascular evaluation and management., Competing Interests: All authors declare no competing interests., (© 2024 The Authors.)

Biopolymers, especially polysaccharides and proteins, are the promising green replacement for petroleum based polymers. Due to their innate properties, they are effectively used in biomedical applications, especially tissue engineering, wound healing, and drug delivery. The fibrous morphology of biopolymers is essentially required for the effectiveness in these biomedical applications. Electrospinning (ES) is the most advanced and robust method to fabricate nanofibers (NFs) and provides a complete solution to the conventional methods issues. However, the major issues regarding fabricating polysaccharides and protein nanofibers using ES include poor electrospinnability, lack of desired fundamental properties for a specific application by a single biopolymer, and insolubility among common solvents. The current review provides the main strategies for effective electrospinning of the major biopolymers. The key strategies include blending major biopolymers with suitable biopolymers and optimizing the solvent system. A systematic literature review was done to provide the optimized solvent system of the major biopolymers along with their best possible biopolymeric blend for ES. The review also highlights the fundamental issues with the commercialization of ES based biomedical products and provides future directions to improve the fabrication of biopolymeric nanofibers., Competing Interests: Declaration of competing interest The authors state that no potential conflicts of interest or personal ties might have influenced the work reported in this research., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Lockdown measures implemented during the initial phase of the pandemic resulted in the delay and disruption of healthcare utilization for individuals with chronic conditions. We aimed to evaluate the impact of COVID-19 movement restrictions on the follow-up care visits of individuals with chronic illnesses. We also assessed the possible reasons patients missed their follow-ups and the potential barriers impeding follow-up during the pandemic., Methods: A total of 397 adults with pre-existing medical conditions participated in an online cross-sectional survey from October to December 2022. The study sample comprised 57 % females and 43 % males, with a mean age of 43 years. A 36-item online self-report survey was used for data collection. Results: Fifty-five percent of participants reported missing their follow-up during COVID-19 pandemic, and 14 % made emergency department visits due to their missed follow-up appointments. In addition, 24 % experienced complications due to their missed appointments. The mean score on the fear of COVID-19 scale was 17.8 ± 6.5 (SD). For the majority of participants (60 %), pandemic-related restrictions were the predominant barrier to their follow-up visits. Additionally, we found that as individuals' COVID-19 fear scores increased, the likelihood of missing a follow-up care visit also increased (AOR: 1.067; p-value = 0.001). However, participants who did not perceive COVID-19 pandemic-related restrictions as a barrier were less likely to miss their follow-up visits (AOR: 0.581; p-value = 0.031). Furthermore, those who understood the significance of follow-up care were less likely to miss any of their follow-up visits (AOR: 0.224; p-value < 0.001) than those who had limited understanding of its importance., Conclusion: The results showed that pandemic-related movement restrictions negatively affected attendance at follow-up visits for people with pre-existing health conditions. Initiatives should therefore be undertaken during global public health emergencies to provide medical and psychological support to vulnerable and high-risk groups., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

UAVs need to communicate along three dimensions (3D) with other aerial vehicles, ranging from above to below, and often need to connect to ground stations. However, wireless transmission in 3D space significantly dissipates power, often hindering the range required for these types of links. Directional transmission is one way to efficiently use available wireless channels to achieve the desired range. While multiple-input multiple-output (MIMO) systems can digitally steer the beam through channel matrix manipulation without needing directional awareness, the power resources required for operating multiple radios on a UAV are often logistically challenging. An alternative approach to streamline resources is the use of phased arrays to achieve directionality in the analog domain, but this requires beam sweeping and results in search-time delay. The complexity and search time can increase with the dynamic mobility pattern of the UAVs in aerial networks. However, if the direction of the receiver is known at the transmitter, the search time can be significantly reduced. In this work, multi-antenna channels between two UAVs in A2A links are analyzed, and based on these findings, an efficient machine learning-based method for estimating the direction of a transmitting node using channel estimates of 4 antennas (2 × 2 MIMO) is proposed. The performance of the proposed method is validated and verified through in-field drone-to-drone measurements. Findings indicate that the proposed method can estimate the direction of the transmitter in the A2A link with 86% accuracy. Further, the proposed direction estimation method is deployable for UAV-based massive MIMO systems to select the directional beam without the need to sweep or search for optimal communication performance.

This manuscript describes the implementation and initial evaluation of a novel Canadian acute care pathway for people with a diabetic foot ulcer (DFU). A multidisciplinary team developed and implemented an acute care pathway for patients with a DFU who presented to the emergency department (ED) and required hospitalisation at a tertiary care hospital in Canada. Processes of care, length of stay (LOS), and hospitalisation costs were considered through retrospective cohort study of all DFU hospitalizations from pathway launch in December 2018 to December 2020. There were 82 DFU-related hospital admissions through the ED of which 55 required invasive intervention: 28 (34.1%) minor amputations, 16 (19.5%) abscess drainage and debridement, 6 (7.3%) lower extremity revascularisations, 5 (6.1%) major amputations. Mean hospital LOS was 8.8 ± 4.9 days. Mean hospitalisation cost was $20 569 (±14 143): $25 901 (±15 965) when surgical intervention was required and $9279 (±7106) when it was not. LOS and hospitalisation costs compared favourably to historical data. An acute care DFU pathway can support the efficient evaluation and management of patients hospitalised with a DFU. A dedicated multidisciplinary DFU care team is a valuable resource for hospitals in Canada., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Angiogenesis plays an important role in peripheral artery disease (PAD) and angiogenesis-related proteins may act as prognostic biomarkers. This study assesses the potential for angiogenesis-related proteins to predict adverse events associated with PAD., Methods: This was a case-control study. Patients with PAD (n = 250) and without PAD (n = 125) provided blood samples and were followed prospectively for three years. Concentrations of 17 angiogenesis-related proteins were measured in plasma. The incidence of major adverse limb event (MALE), defined as a composite of major amputation or vascular intervention, was the primary outcome. Worsening PAD status, defined as a drop in ankle brachial index ≥ 0.15, was the secondary outcome. Multivariable regression adjusted for baseline characteristics was conducted to determine the prognostication value of angiogenesis-related proteins in predicting MALE., Findings: Relative to patients without PAD, 8 proteins related to angiogenesis were expressed differentially in PAD patients. Worsening PAD status and MALE were observed in 52 (14%) and 83 (22%) patients, respectively. Hepatocyte growth factor (HGF) was the most reliable predictor of MALE (adjusted HR 0.79, 95% CI 0.15-0.86). Compared to individuals with high HGF, patients with low HGF had a decreased three-year freedom from MALE [66% vs 88%, p = 0.001], major amputation [93% vs 98%, p = 0.023], vascular intervention [68% vs 88%, p = 0.001], and worsening PAD status [81% vs 91%, p = 0.006]., Interpretation: Measuring plasma levels of HGF in individuals with PAD can assist in identifying patients at elevated risk of adverse events related to PAD who may benefit from additional evaluation or treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objective: Peripheral artery disease (PAD) remains undertreated, despite its association with major amputation and mortality. This is partly due to a lack of available disease biomarkers. The intracellular protein fatty acid binding protein 4 (FABP4) is implicated in diabetes, obesity, and metabolic syndrome. Given that these risk factors are strong contributors to vascular disease, we assessed the prognostic ability of FABP4 in predicting PAD-related adverse limb events., Methods: This was a prospective case-control study with 3 years of follow-up. Baseline serum FABP4 concentrations were measured in patients with PAD (n = 569) and without PAD (n = 279). The primary outcome was major adverse limb event (MALE; defined as a composite of vascular intervention or major amputation). The secondary outcome was worsening PAD status (drop in ankle-brachial index ≥0.15). Kaplan-Meier and Cox proportional hazards analyses adjusted for baseline characteristics were conducted to assess the ability of FABP4 to predict MALE and worsening PAD status., Results: Patients with PAD were older and more likely to have cardiovascular risk factors compared with those without PAD. Over the study period, MALE and worsening PAD status occurred in 162 (19%) and 92 (11%) patients, respectively. Higher FABP4 levels were significantly associated with 3-year MALE (unadjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.04-1.27; adjusted HR, 1.18; 95% CI, 1.03-1.27; P = .022) and worsening PAD status (unadjusted HR, 1.18; 95% CI, 1.13-1.31; adjusted HR, 1.17; 95% CI, 1.12-1.28; P < .001). Three-year Kaplan-Meier survival analysis demonstrated that patients with high FABP4 levels had a decreased freedom from MALE (75% vs 88%; log rank = 22.6; P < .001), vascular intervention (77% vs 89%; log rank = 20.8; P < .001), and worsening PAD status (87% vs 91%; log rank = 6.16; P = .013)., Conclusions: Individuals with higher serum concentrations of FABP4 are more likely to develop PAD-related adverse limb events. FABP4 has prognostic value in risk-stratifying patients for further vascular evaluation and management., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Carotid artery stenosis (CAS), an atherosclerotic disease of the carotid artery, is one of the leading causes of transient ischemic attacks (TIA) and cerebrovascular attacks (CVA). The atherogenic process of CAS affects a wide range of physiological processes, such as inflammation, endothelial cell function, smooth muscle cell migration and many more. The current gold-standard test for CAS is Doppler ultrasound; however, there is yet to be determined a strong, clinically validated biomarker in the blood that can diagnose patients with CAS and/or predict adverse outcomes in such patients. In this comprehensive literature review, we evaluated all of the current research on plasma and serum proteins that are current contenders for biomarkers for CAS. In this literature review, 36 proteins found as potential biomarkers for CAS were categorized in to the following nine categories based on protein function: (1) Inflammation and Immunity, (2) Lipid Metabolism, (3) Haemostasis, (4) Cardiovascular Markers, (5) Markers of Kidney Function, (6) Bone Health, (7) Cellular Structure, (8) Growth Factors, and (9) Hormones. This literature review is the most up-to-date and current comprehensive review of research on biomarkers of CAS, and the only review that demonstrated the several pathways that contribute to the initiation and progression of the disease. With this review, future studies can determine if any new markers, or a panel of the proteins explored in this study, may be contenders as diagnostic or prognostic markers for CAS.

Cadmium (Cd) is a heavy metal with various human exposure sources. It accumulates in the liver, forming a complex with metallothionein protein and progresses to other organs. As a heavy metal, cadmium can replace calcium and other divalent ions and disturb their cascades, ultimately affecting the vital organs. Since cadmium acetate (CA) is considered more lethal than other Cd compounds, the current study examines the effect of different concentrations of CA doses in drinking water for different exposure times in murine models (Mus musculus). After the exposure period, the murine models were then examined histopathologically and biochemically. The histopathological examination of the heart, liver, and kidneys of the experimental group showed extensive degenerative effects. Atomic absorption spectroscopy was used to determine the quantity of cadmium in serum, kidney, and hepatic tissues. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of hepatic proteins, especially metallothionein, directly related to Cd administration. The biochemical parameters, including creatine kinase, alanine aminotransferase, aspartate aminotransferase, total proteins, glucose, urea, uric acid, and creatinine, were also analyzed. After thorough histochemical and biochemical analysis, it was concluded that even low dose exposure of CA is hazardous to murine models with damaging effects., (© 2023 Wiley Periodicals LLC.)

Background: Inappropriate use of medications is a global health concern, and this is attributed to the increased accessibility to prescription and non-prescription (over-the-counter) drugs at community pharmacies. We investigated the inappropriate use of prescription and non-prescription drugs in community pharmacies based on the perspectives of the community pharmacists in Saudi Arabia., Methods: This was a questionnaire-based, cross-sectional survey which employed convenient sampling (snowball technique) to recruit participants. Being a licensed practicing pharmacist in a retail chain or an independent community pharmacy was the inclusion criteria. Participants were asked to report the drugs they suspected of being inappropriately used along with the frequency, age and gender of the suspected customers. Pharmacists were also asked to mention the action taken to limit inappropriate use at their pharmacy., Results: A total of 397 community pharmacists completed the questionnaire (86.9 % response rate). 86.4% of the pharmacists suspected some level of abuse or misuse to have occurred. After receiving the questionnaire, the pharmacists reported suspected inappropriate use as encountered during the past three months. Cumulative inappropriate use was reported 1069 times (prescription drugs - 530; non-prescription drugs - 539). The top three inappropriately used prescription-drug categories were gabapentinoids (22.5%), antipsychotics (17.5%) and topical corticosteroids (12.1%). Among non-prescription drugs, cough products (33.2%) ranked first, followed by cold and flu products (29.5%) and first-generation antihistamines (10.8%). The cross tabulations revealed that being in the age range of 26-50 years and being a male was significantly associated (p < 0.001) with abuse/misuse of antipsychotics, antidepressants, gabapentinoids, cough products and first-generation antihistamines. Eye products (Bimatoprost) and skin products abuse/misuse had significant association with female gender (p < 0.001)., Conclusion: The results of our study provide crucial information to the healthcare authorities regarding the medications that can be inappropriately used at the community pharmacies in Saudi Arabia which necessitates implementation of stringent dispensing regulations. Educational programs can be implemented to increase the awareness among public regarding the harmful effects of inappropriate use of drugs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Proper functioning of the nervous system relies not only on the generation of a vast repertoire of distinct neural cell types but also on the precise neural circuitry within them. How the generation of highly diverse neural populations is regulated during development remains a topic of interest. Landmark studies in Drosophila have identified the genetic and temporal cues regulating neural diversity and thus have provided valuable insights into our understanding of temporal patterning of the central nervous system. The development of the Drosophila central complex, which is mostly derived from type II neural stem cell (NSC) lineages, showcases how a small pool of NSCs can give rise to vast and distinct progeny. Similar to the human outer subventricular zone (OSVZ) neural progenitors, type II NSCs generate intermediate neural progenitors (INPs) to expand and diversify lineages that populate higher brain centers. Each type II NSC has a distinct spatial identity and timely regulated expression of many transcription factors and mRNA binding proteins. Additionally, INPs derived from them show differential expression of genes depending on their birth order. Together type II NSCs and INPs display a combinatorial temporal patterning that expands neural diversity of the central brain lineages. We cover advances in current understanding of type II NSC temporal patterning and discuss similarities and differences in temporal patterning mechanisms of various NSCs with a focus on how cell-intrinsic and extrinsic hormonal cues regulate temporal transitions in NSCs during larval development. Cell extrinsic ligands activate conserved signaling pathways and extrinsic hormonal cues act as a temporal switch that regulate temporal progression of the NSCs. We conclude by elaborating on how a progenitor's temporal code regulates the fate specification and identity of distinct neural types. At the end, we also discuss open questions in linking developmental cues to neural identity, circuits, and underlying behaviors in the adult fly., Competing Interests: Conflict of interests None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Globally, adverse drug reactions (ADRs) are the foremost cause of morbidity as well as mortality. This necessitates a system of surveillance that can effectively and efficiently monitor the effect of drugs on the general population. The role of pharmacovigilance (PV) is paramount in ensuring drug safety through spontaneous ADR reporting., Methods: Data collection in the current research was carried out by an anonymous, online 36-item self-report questionnaire amongst a sample of 351 working healthcare professionals (HCPs) across different regions of Jazan Province, Kingdom of Saudi Arabia (KSA). The current sample comprised 54.4% males and 45.6% females, having an age range of 26-57 years, and was conducted between August 21 and October 21, 2022. Participants were recruited using the convenience snowball sampling technique., Results: The participants' awareness of PV as well as spontaneous ADR reporting, had a significant association with having <40 years of age ( χ 2  =  27.40 ; p <  0.001), being pharmacists ( χ 2  =  212.20; p <  0.001), with more than five years of experience ( χ 2  =  40.80 ; p <  0.001), having Masters (or) Doctorate/Fellowship ( χ 2  =  171.94; p <  0.001), and having their practice located in an urban area ( χ 2  =  50.30 ; p <  0.001). It was also observed that most participants with excellent awareness of PV and spontaneous ADR reporting also demonstrated excellent attitudes ( χ 2  = 147.70; p <  0.001). Similarly, it was also seen that almost all (97%) of the study sample with excellent attitudes towards PV and spontaneous ADR reporting also demonstrated excellent practices ( χ 2  = 250.73; p < 0.001)., Conclusion: Our results demonstrate a need for designing and conducting educational programs, providing training and conducting workshops for all the HCPs to improve their awareness towards PV and spontaneous ADR reporting while also highlighting the need and importance of having positive attitudes towards spontaneous ADR reporting. Cooperation between different HCPs should be encouraged to improve their practices towards spontaneous ADR reporting., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background and Aims: Systolic blood pressure interarm difference (IAD) predicts cardiovascular morbidity and mortality in primary prevention populations. We examined the predictive value of IAD and the effects of treatment with the combination of rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily versus aspirin 100 mg once daily according to IAD in patients with chronic coronary artery disease or peripheral artery disease., Methods: COMPASS trial patients with IAD <15 mmHg and IAD >15 mmHg were compared with respect to thirty-month incidence risk of: 1) composite of stroke, myocardial infarction, or cardiovascular death (MACE), 2) composite of acute limb-ischemia or vascular amputation (MALE), 3) composite of MACE or MALE, and 4) effects of treatment with the combination versus aspirin alone on these outcomes., Results: 24,539 patients had IAD<15 mmHg and 2,776 had IAD ≥15 mmHg. Relative to patients with IAD ≥15 mm Hg, those with IAD<15 mmHg had similar incidence rates for all measured outcomes including the composite of MACE or MALE (HR 1.12 [95% CI: 0.95 to 1.31], p = 0.19), with the exception of stroke (HR 1.38 [95% CI: 1.02 to 1.88], p = 0.04). Compared to aspirin alone, the combination consistently reduced the composite of MACE or MALE in both IAD <15 mmHg (HR 0.74 [95% CI: 0.65-0.85], p < 0.0001, ARR = -23.1) and IAD>15 mmHg (HR 0.65 [95% CI: 0.44-0.96], p = 0.03; ARR = -32.6, p interaction = 0.53) groups., Conclusions: Unlike primary prevention populations, measuring IAD for risk stratification purposes does not appear to be useful in patients with established vascular disease., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Connolly reports personal fees from BMS, Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Portola during the conduct of the study. k. Dr Bosch reported receiving honararium and salary support for conducting research from Bayer. Dr. Eikelboom reports honoraria and grant support from Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Sanofi Aventis, and Eli Lilly as well as a personnel award from the Heart and Stroke Foundation. Dr. Anand, receiving lecture fees from Bayer and Janssen. Dr Muehlhofer, being employed by Bayer. Dr Aboyans reports grants and/or honoraria for speaking and consulting from Bayer, Bristol Myers Squibb, Novartis, and Pfizer and personal fees from Boehringer Ingelheim, Amgen, and Bristol Myers Squibb/Pfizer Alliance. Dr. Yusuf reported grants and personal fees from and has received research grants and honoraria and travel reimbursement for speaking from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, AstraZeneca, Cadila Pharmaceuticals, and Sanofi Aventis., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

With the advent of modern information systems, sharing Electronic Health Records (EHRs) with different organizations for better medical treatment, and analysis is beneficial for both academic as well as for business development. However, an individual's personal privacy is a big concern because of the trust issue across organizations. At the same time, the utility of the shared data that is required for its favorable use is also important. Studies show that plenty of conventional work is available where an individual has only one record in a dataset (1:1 dataset), which is not the case in many applications. In a more realistic form, an individual may have more than one record in a dataset (1:M). In this article, we highlight the high utility loss and inapplicability for the 1:M dataset of the θ -Sensitive k -Anonymity privacy model. The high utility loss and low data privacy of ( p ,  l )-angelization, and ( k ,  l )-diversity for the 1:M dataset. As a mitigation solution, we propose an improved ( θ ∗ ,  k )-utility algorithm to preserve enhanced privacy and utility of the anonymized 1:M dataset. Experiments on the real-world dataset reveal that the proposed approach outperforms its counterpart, in terms of utility and privacy for the 1:M dataset., Competing Interests: The authors declare there are no competing interests., (©2023 Fazal et al.)

Stem cells must balance proliferation and quiescence, with excess proliferation favoring tumor formation, and premature quiescence preventing proper organogenesis. Drosophila brain neuroblasts are a model for investigating neural stem cell entry and exit from quiescence. Neuroblasts begin proliferating during embryogenesis, enter quiescence prior to larval hatching, and resume proliferation 12-30h after larval hatching. Here we focus on the mechanism used to exit quiescence, focusing on "type II" neuroblasts. There are 16 type II neuroblasts in the brain, and they undergo the same cycle of embryonic proliferation, quiescence, and proliferation as do most other brain neuroblasts. We focus on type II neuroblasts due to their similar lineage as outer radial glia in primates (both have extended lineages with intermediate neural progenitors), and because of the availability of specific markers for type II neuroblasts and their progeny. Here we characterize the role of Insulin-like growth factor II mRNA-binding protein (Imp) in type II neuroblast proliferation and quiescence. Imp has previously been shown to promote proliferation in type II neuroblasts, in part by acting antagonistically to another RNA-binding protein called Syncrip (Syp). Here we show that reducing Imp levels delays exit from quiescence in type II neuroblasts, acting independently of Syp, with Syp levels remaining low in both quiescent and newly proliferating type II neuroblasts. We conclude that Imp promotes exit from quiescence, a function closely related to its known role in promoting neuroblast proliferation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Munroe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patients with peripheral arterial disease (PAD) often remain undiagnosed and therefore suboptimally managed. Here, we investigated the diagnostic and prognostic potential of fatty acid binding protein 3 (FABP3) in patients with PAD., Methods: In the discovery phase, 374 PAD and 184 non-PAD patients were recruited from vascular surgery ambulatory clinics at St. Michael's Hospital (Toronto, Ontario, Canada) between October 4, 2017 to October 29, 2018. The diagnostic ability of baseline FABP3 level was investigated through receiver operator characteristic (ROC) curves to determine two cutoff points: 1) an exclusionary "rule out" cutoff point, and 2) a confirmatory "rule in" cutoff point. Next, these cutoff points were confirmed in the external validation phase using a separate cohort of 312 patients (180 PAD and 132 non-PAD) recruited from ambulatory vascular surgery clinics at St. Michael's Hospital (Canada) between November 6, 2018-July 30, 2019. Cox regression analyses were used to explore the independent association between FABP3 and major adverse limb events (MALE - defined as need for arterial revascularization or major amputation) and decrease in ankle-brachial index (ABI -defined as drop ≥0.15) during 3 years of follow-up., Findings: In the discovery phase, FABP3 levels were significantly elevated in patients with PAD compared to non-PAD patients. ROC analysis demonstrated that FABP3 had an AUC of 0.83 (95% CI: 0.81-0.86, p-value < 0.001). FABP3 exclusionary cutoff was <1.55 ng/ml (sensitivity = 96%; specificity = 40%), whereas FABP3 confirmatory cutoff was >3.55 ng/ml (sensitivity = 43%; specificity = 95%) - values that were confirmed in the external validation phase. Cox regression analysis demonstrated FABP3 to be an independent predictor of increase in MALE [HR = 1.14 (1.03-1.29); p-value = 0.010] and worsening PAD status (drop in ABI >0.15 [HR = 1.11 (1.02-1.19); p-value = 0.009])., Interpretation: Our findings suggested that FABP3 levels can be used as both a diagnostic and prognostic biomarker for PAD, and may facilitate risk stratification in select individuals for purposes of vascular evaluation or intensive medical management., Funding: Funding for this study was provided by the Bill and Vicky Blair Foundation., Competing Interests: Dr. John Eikelboom reports consulting fees/honoraria and/or grant support from 10.13039/100004325AstraZeneca, Bayer Boehringer-Ingelheim, Bristol-Myer-Squibb/10.13039/100004319Pfizer, 10.13039/501100002973Daiichi-Sankyo, 10.13039/100004312Eli Lilly & Co, 10.13039/100004330GlaxoSmithKline, 10.13039/100004319Pfizer, 10.13039/100005565Janssen, 10.13039/100004339sanofi-aventis, 10.13039/501100011725Servier. The remaining authors have nothing to disclose., (© 2022 The Authors.)

Background: Levels of inflammatory proteins and their prognostic potential have been inadequately studied in patients with peripheral artery disease (PAD). In this study, we quantified and assessed the ability of inflammatory proteins in predicting PAD-related adverse events., Methods: In this prospective case-control study, blood samples were collected from patients without PAD ( n = 202) and patients with PAD ( n = 275). The PAD cohort was stratified by disease severity based on ankle brachial index (ABI): mild ( n = 49), moderate ( n = 164), and severe ( n = 62). Patients were followed for 2 years. Plasma concentrations of 5 inflammatory proteins were measured: Alpha-2-Macroglobulin (A2M), Fetuin A, Alpha-1-Acid Glycoprotein (AGP), Serum Amyloid P component (SAP), and Adipsin. The primary outcome of our study was major adverse limb event (MALE), defined as the need for vascular intervention (open or endovascular revascularization) or major amputation. The secondary outcome was worsening PAD status, defined as a drop in ABI greater than or equal to 0.15 over the study period. Multivariable logistic regression was performed to assess the prognostic value of inflammatory proteins in predicting MALE, adjusting for confounding variables., Results: Compared to patients without PAD, three inflammatory proteins were differentially expressed in patients with PAD (AGP, Fetuin A, and SAP). The primary outcome (MALE) and secondary outcome (worsening PAD) status were noted in 69 (25%) and 60 (22%) patients, respectively. PAD-related adverse events occurred more frequently in severe PAD patients. Based on our data, the inflammatory protein AGP was the most reliable predictor of primary and secondary outcomes. On multivariable analysis, there was a significant association between AGP and MALE in all PAD disease states [mild: adjusted HR 1.13 (95% CI 1.05-1.47), moderate: adjusted HR 1.23 (95% CI 1.16-1.73), severe: adjusted HR 1.37 (95% CI 1.25-1.85)]. High levels of AGP were associated with lower 2-year MALE-free survival in all PAD disease states [mild (64% vs. 100%, p = 0.02), moderate (64% vs. 85%, p = 0.02), severe (55% vs. 88%, p = 0.02), all PAD (62% vs. 88%, p = 0.01)]., Conclusion: Levels of inflammatory protein AGP may help in risk stratifying PAD patients at high risk of MALE and worsening PAD status and subsequently facilitate further vascular evaluation and initiation of aggressive medical/surgical management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Djahanpour, Zamzam, Syed, Jain, Arfan, Abdin and Qadura.)

Blood-based adjunctive measures that can reliably predict abdominal aortic aneurysm (AAA)-related complications hold promise for mitigating the AAA disease burden. In this pilot study, we sought to evaluate the prognostic performance of complement factors in predicting AAA-related clinical outcomes. We recruited consecutive AAA patients (n = 75) and non-AAA patients (n = 75) presenting to St. Michael's Hospital. Plasma levels of complement proteins were assessed at baseline, as well as prospectively measured regularly over a period of 2 years. The primary outcome was the incidence of rapidly progressing AAA (i.e. aortic expansion), defined as change in AAA diameter by either 0.5 cm in 6 months, or 1 cm in 12 months. Secondary outcomes included incidence of major adverse aortic events (MAAE) and major adverse cardiovascular events (MACE). All study outcomes (AAA diameter, MACE and MAAE) were obtained during follow-up. Multivariable adjusted Cox regression analyses were performed to assess the prognostic value of plasma C2 levels in patients with AAA regarding rapid aortic expansion and MAAE and MACE. Event-free survival rates of both groups were also compared. Compared to non-AAA patients, patients with AAA demonstrated significantly higher plasma concentrations of C1q, C4, Factor B, Factor H and Factor D, and significantly lower plasma concentrations of C2, C3, and C4b (p = 0.001). After a median of 24 months from initial baseline measurements, C2 was determined as the strongest predictor of rapid aortic expansion (HR 0.10, p = 0.040), MAAE (HR 0.09, p = 0.001) and MACE (HR 0.14, p = 0.011). Based on the data from the survival analysis, higher levels of C2 at admission in patients with AAA predicted greater risk for rapid aortic expansion and MAAE (not MACE). Plasma C2 has the potential to be a biomarker for predicting rapid aortic expansion, MAAE, and the eventual need for an aortic intervention in AAA patients., (© 2022. The Author(s).)

First aid is the most basic and life-saving service provided before emergency care is received. This study aimed to assess students' knowledge and attitudes about performing first aid for snakebite emergencies and their perception of snakes. A cross-sectional study was conducted between January and March 2019 among upper-level students (3rd year and above) of health-related courses at Jazan University, Saudi Arabia. Three hundred and nine students from four programs responded to the self-administered questionnaire. The collected data were analyzed using SPSS 23.0. The highest percentage of the study sample comprised pharmacy students (44%), followed by nursing (25.2%), medical (16.8%), and emergency medicine students (13.9%). Overall, the emergency medicine students exhibited greater knowledge of snakebite first aid. However, over three-fourths of the students were unaware of dry bites. Around two-thirds were sure that they should not massage the bite site, while nearly one-fourth were not sure about the use of a tourniquet. The fifth- and sixth-year students had extremely diverse perspectives on snakes. The majority of the participants (92.8%) did not feel good about snakes. However, most of the students (95.2%) wanted to learn about snakebite first aid and overcome their fear of snakes. Overall, the students had a positive attitude towards first aid but lacked knowledge of snakebite emergencies. Public health awareness is required to dispel first-aid myths about snakebites and misconceptions regarding snakes.

Aspirin resistance describes a phenomenon where patients receiving aspirin therapy do not respond favorably to treatment, and is categorized by continued incidence of adverse cardiovascular events and/or the lack of reduced platelet reactivity. Studies demonstrate that one in four patients with vascular disease are resistant to aspirin therapy, placing them at an almost four-fold increased risk of major adverse limb and adverse cardiovascular events. Despite the increased cardiovascular risk incurred by aspirin resistant patients, strategies to diagnose or overcome this resistance are yet to be clinically validated and integrated. Currently, five unique laboratory assays have shown promise for aspirin resistance testing: Light transmission aggregometry, Platelet Function Analyzer-100, Thromboelastography, Verify Now, and Platelet Works. Newer antiplatelet therapies such as Plavix and Ticagrelor have been tested as an alternative to overcome aspirin resistance (used both in combination with aspirin and alone) but have not proven to be superior to aspirin alone. A recent breakthrough discovery has demonstrated that rivaroxaban, an anticoagulant which functions by inhibiting active Factor X when taken in combination with aspirin, improves outcomes in patients with vascular disease. Current studies are determining how this new regime may benefit those who are considered aspirin resistant.

Fatty acid binding proteins (FABPs) are proteins found in the cytosol that contribute to disorders related to the cardiovascular system, including atherosclerosis and metabolic syndrome. Functionally, FABPs serve as intracellular lipid chaperones, interacting with hydrophobic ligands and mediating their transportation to sites of lipid metabolism. To date, nine unique members of the FABP family (FABP 1-9) have been identified and classified according to the tissue in which they are most highly expressed. In the literature, FABP3 has been shown to be a promising clinical biomarker for coronary and peripheral artery disease. Given the rising incidence of cardiovascular disease and its associated morbidity/mortality, identifying biomarkers for early diagnosis and treatment is critical. In this review, we highlight key discoveries and recent studies on the role of FABP3 in cardiovascular disorders, with a particular focus on its clinical relevance as a biomarker for peripheral artery disease.

Approximately 20% of vascular patients treated with acetyl salicylic acid (i.e., aspirin) demonstrate less than expected platelet inhibition - putting them at a four-fold increased risk of adverse cardiovascular events. Low-dose rivaroxaban (2.5 mg twice daily) in combination with low-dose aspirin has been shown to reduce adverse cardiovascular and limb events when compared to aspirin alone. In this study, light transmission aggregometry was used to measure arachidonic acid-induced platelet aggregation to evaluate the potential of combining low-dose rivaroxaban and aspirin in attenuating or overcoming aspirin non-sensitivity. In the discovery phase, 83 patients with peripheral arterial disease (PAD) taking 81 mg aspirin daily were recruited from the outpatient vascular surgery clinic at St Michael's Hospital between January to September 2021. 19 (23%) were determined to be non-sensitive to aspirin. After ex-vivo addition of 2.5 mg dosage equivalent of rivaroxaban, aspirin non-sensitivity was overcome in 11 (58%) of these 19 patients. In the validation phase, 58 patients with cardiovascular risk factors who were not previously prescribed aspirin were recruited. In this group, ex-vivo addition of 2.5 mg dosage equivalent of rivaroxaban significantly reduced arachidonic acid-induced platelet aggregation in the presence of aspirin. These results demonstrate the potential for low-dose rivaroxaban to overcome aspirin non-sensitivity in patients with PAD. Further studies are needed to evaluate and confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khan, Popkov, Jain, Djahanpour, Syed, Rand, Eikelboom, Mazer, Al-Omran, Abdin and Qadura.)

To navigate towards a food source, animals frequently combine odor cues about source identity with wind direction cues about source location. Where and how these two cues are integrated to support navigation is unclear. Here we describe a pathway to the Drosophila fan-shaped body that encodes attractive odor and promotes upwind navigation. We show that neurons throughout this pathway encode odor, but not wind direction. Using connectomics, we identify fan-shaped body local neurons called h∆C that receive input from this odor pathway and a previously described wind pathway. We show that h∆C neurons exhibit odor-gated, wind direction-tuned activity, that sparse activation of h∆C neurons promotes navigation in a reproducible direction, and that h∆C activity is required for persistent upwind orientation during odor. Based on connectome data, we develop a computational model showing how h∆C activity can promote navigation towards a goal such as an upwind odor source. Our results suggest that odor and wind cues are processed by separate pathways and integrated within the fan-shaped body to support goal-directed navigation., (© 2022. The Author(s).)

Despite its association with adverse outcomes, peripheral artery disease (PAD) remains undertreated. Cystatin C is elevated in patients with renal disease and may be a marker of cardiovascular disease. We examined the prognostic ability of urinary Cystatin C (uCystatinC) in predicting adverse PAD-related events. In this prospective case-control study, urine samples were collected from patients with PAD ( n = 121) and without PAD ( n = 77). The cohort was followed for 2 years. uCystatinC was normalized to urinary creatinine (uCr) (uCystatinC/uCr; μg/g). The primary outcome was major adverse limb event (MALE; composite of vascular intervention (open or endovascular) or major limb amputation). The secondary outcome was worsening PAD status (drop in ABI ≥ 0.15). Multivariable Cox regression and Kaplan-Meier analyses were performed to assess the prognostic value of uCystatinC/uCr with regards to predicting MALE and worsening PAD status. Our analysis demonstrated that patients with PAD had significantly higher median [IQR] uCystatinC/uCr levels (24.9 μg/g [14.2-32.9] vs. 20.9 μg/g [11.1-27.8], p = 0.018). Worsening PAD status and MALE were observed in 39 (20%) and 34 (17%) patients, respectively. uCystatinC/uCr predicted worsening PAD status with a hazard ratio (HR) of 1.78 (95% CI 1.12-2.83, p = 0.015), which persisted after controlling for baseline demographic and clinical characteristics (adjusted HR 1.79 [95% CI 1.11-2.87], p = 0.017). Patients with high uCystatinC/uCr had a lower 2-year freedom from MALE (77% vs. 89%, p = 0.025) and worsening PAD status (63% vs. 87%, p = 0.001). Based on these data, higher uCystatinC/uCr levels are associated with adverse PAD-related events and have prognostic value in risk-stratifying individuals for further diagnostic vascular evaluation or aggressive medical management.

Background: Despite its significant association with limb loss and death, peripheral artery disease (PAD) remains underdiagnosed and undertreated. The current accepted gold-standard for PAD screening, the ankle brachial index (ABI), is limited by operator dependence, erroneous interpretation, and unreliability in patients with diabetes. Fatty acid binding protein 3 (FABP3) is an intracellular protein that becomes released into circulation and excreted into urine following skeletal muscle injury. We examined the prognostic ability of urinary FABP3 (uFABP3) in predicting adverse PAD-related events., Methods: In this prospective case-control study, urine samples were collected from patients with PAD ( n = 142) and without PAD ( n = 72). The cohort was followed for 2 years. uFABP3 was normalized to urinary creatinine (uCr) (uFABP3/uCr). The primary outcome was major adverse limb event (MALE; composite of vascular intervention [open or endovascular] or major limb amputation). The secondary outcome was worsening PAD status (drop in ABI≥0.15). Cox regression analyses with multivariable adjustment for baseline demographic and clinical variables were performed to assess the prognostic value of uFABP3/uCr with regards to predicting MALE and worsening PAD status., Results: Patients with PAD had significantly higher median [IQR] uFABP3/uCr levels (3.46 [2.45-6.90] vs. 2.61 [1.98-4.62], p = 0.001). MALE and worsening PAD status were observed in 21 (10%) and 28 (14%) patients, respectively. uFABP3/uCr predicted MALE and worsening PAD status with adjusted hazard ratios (HR) of 1.28 (1.16-1.41, p = 0.001) and 1.16 (1.02-1.27, p = 0.021), respectively. Patients with high uFABP3/uCr had a lower 2-year freedom from MALE (86 vs. 96%, p = 0.047) and worsening PAD status (78 vs. 99%, p = 0.001). There was good discriminatory ability for uFABP3/uCr in predicting the primary outcome of MALE, with an area under the receiver operating characteristics curve (AUROC) of 0.78., Conclusions: Measuring uFABP3/uCr levels in patients with PAD can help identify those at high risk of adverse PAD-related events. This study highlights the prognostic value of uFABP3 in risk-stratifying individuals for further diagnostic vascular evaluation or aggressive medical management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Zamzam, Syed, Jahanpour, Jain, Abdin and Qadura.)

Background: Diabetic foot ulcers (DFUs) are common and disabling, necessitating lengthy hospitalizations. In this study we sought to identify potentially modifiable determinants of high-intensity hospital care use among adults with DFUs., Methods: Three related case-control studies were conducted using Canada-wide cohorts of adults hospitalized with a DFU from 2011 to 2015. In study 1, cases comprised the top 10% with the highest cumulative 1-year acute care hospital costs; controls were randomly selected from those below the top 10%. Study 2 comprised cases/controls within/below the top 10% for cumulative acute care hospital length of stay (LOS). Study 3 included cases/controls within/below the top 10% for cumulative number of acute care hospitalizations. Using generalized linear models, predictor variables were tested between cases and controls, while adjusting for age and sex., Results: In study 1, mean acute care costs among 8,971 cases and 3,174 controls were $71,757 and $13,687, respectively. Sepsis conferred the greatest excess cost (mean, $38,790; 95% confidence interval [CI], $34,597 to $43,508), followed by chronic kidney disease (mean, $30,607; 95% CI, $28,389 to $32,825) and major lower limb amputation (mean, $30,884; 95% CI, $28,613 to $33,155). In study 2, mean LOS was higher among 8,477 cases (69 days) than 3,467 controls (12 days). Lower limb amputation conferred the greatest adjusted excess in mean LOS (mean, 28 days; 95% CI, 27 to 28 days). In study 3, there was a mean of 3 hospitalizations among 10,341 cases and 1 among 5,509 controls. Peripheral artery disease conferred the greatest excess number of hospitalizations (1.3 more hospitalizations; 1.2 to 1.4)., Conclusions: Early aggressive treatment of chronic kidney disease and peripheral artery disease, alongside guideline-based amputation prevention strategies, may reduce high-intensity hospital care use among adults with DFUs., (Copyright © 2021 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in atherosclerotic plaques and implicated in the development of cardiovascular diseases. Peripheral arterial disease (PAD) is an atherosclerotic disease that often results in major cardiovascular events. This study aimed to prospectively examine the potential of urine NGAL (uNGAL) in predicting worsening PAD status and major adverse limb events (MALE). Baseline urine NGAL (uNGAL) and urine creatinine (uCr) concentrations were measured in PAD (n = 121) and non-PAD (n = 77) patients. Levels of uNGAL were normalized for urine creatinine (uNGAL/uCr). Outcomes included worsening PAD status, which was defined as a drop in ankle brachial index (ABI) > 0.15, and major adverse limb events (MALE), which was defined as a need for surgical revascularization or amputations. PAD patients had 2.30-fold higher levels of uNGAL/uCr [median (IQR) 31.8 (17.0-62.5) μg/g] in comparison to non-PAD patients [median (IQR) 73.3 (37.5-154.7) μg/g] (P = 0.011). Multivariate cox analysis showed that uNGAL/uCr levels were independently associated with predicting worsening PAD status and MALE outcomes. Cumulative survival analysis, over follow up period, demonstrated a direct correlation between elevated uNGAL/uCr levels and PAD disease progression and MALE outcomes. These data demonstrate an association between elevated uNGAL/uCr levels and worsening PAD disease status and MALE outcomes, indicating its potential for risk-stratification of PAD patients., (© 2022. The Author(s).)

D-dimer and prothrombin fragment (F1+2) levels are elevated in patients with peripheral artery disease (PAD). We examined their prognostic potential in predicting decreasing ABI and major adverse limb events (MALE). A total of 206 patients were recruited from St. Michael’s Hospital and followed for two years. Baseline plasma concentrations of D-dimer and F1+2 were recorded. Pearson’s correlation was used to assess the correlation between the biomarkers and ABI at year 2. During follow-up, multivariable Cox proportional hazard analysis was performed to investigate their role in predicting decreasing ABI (defined as change in ABI > −0.15) and MALE (defined as the need for arterial intervention or major limb amputation). Cumulative survival was assessed using Kaplan−Meier analysis. Baseline D-dimer and F1+2 levels were elevated in PAD patients (median (IQR) 1.34 (0.80−2.20) for D-dimer and 3.60 (2.30−4.74) for F1+2; p = 0.001) compared to non-PAD controls (median (IQR) 0.69 (0.29−1.20) for D-dimer and 1.84 (1.17−3.09) for F1+2; p = 0.001). Both markers were negatively correlated with ABI at year 2 (r = −0.231 for D-dimer, r = −0.49 for F1+2; p = 0.001). Cox analysis demonstrated F1+2 and D-dimer to be independent predictors of PAD status (HR = 1.27, 95% CI = 1.15−1.54; p = 0.013 for D-dimer and HR = 1.28, 95% CI = 1.14−1.58; p = 0.019 for F1+2). Elevated baseline concentrations of D-dimer and F1+2 were associated with high incidence of decreasing ABI and 1- and 2-year event-free survival (62% and 86%, respectively). Combined analysis of D-dimer and F1+2 provides important prognostic information that facilitates risk stratification for future disease progression and MALE outcomes in patients with PAD.