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Background: In July 2021, the Alappuzha district in Kerala, India, reported an unexpected number of acute gastroenteritis (772) cases (Outbreak A). On October 10, 2021, a university in Wayanad, Kerala, reported 25 acute gastroenteritis cases (Outbreak B). We described both the outbreaks and determined the agent, source and risk factors., Methods: We defined a suspected case as the occurrence of vomiting or at least three episodes of loose stools within 24 h and a confirmed case as those with stool samples/rectal swabs positive for norovirus. We did a matched case-control study in Outbreak A and a retrospective cohort study in Outbreak B. We calculated the adjusted odds ratio (aOR) in outbreak A, relative risk (aRR) in outbreak B and population attributable fraction (PAF). We tested stool and water samples for bacteria and viruses., Results: We identified Group II norovirus in stool samples in both outbreaks and 4/5 water samples in Outbreak A. Suspected norovirus infection was associated with drinking inadequately boiled water from the municipal water supply in outbreak A [aOR: 4.5; 95 % C.I: 1.2-15.8; PAF: 0.23] and well water in hostels in outbreak B [aRR: 2.2; 95 % C.I: 1.2-3.9; PAF: 0.15]. In Outbreak A, groundwater from tube wells was mixed in the municipal water supply overhead tanks without chlorination., Conclusion: The gastroenteritis outbreaks were caused by Group II norovirus due to the consumption of inadequately boiled contaminated groundwater (outbreak A) and well water (outbreak B). We recommended superchlorination of overhead tanks and wells and boiled water for drinking., Competing Interests: Declaration of Competing Interest 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. Conflict of interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Opioid overdose deaths in the U.S. have risen dramatically in the past decade, largely due to the surge in illicitly manufactured fentanyl. Injection drug use is a known risk factor for HIV, further complicating the long-term consequences of opioid use. The baseline prevalence of HIV among adults in the US is 0.46 %. The primary purpose of this study was to determine the prevalence and risk factors of HIV among patients presenting to the emergency departments (ED) with an acute opioid overdose., Methods: This study is a prospective observational cohort study from the ToxIC Fentalog Study group. Patients age 18 years of age or older are included if they present to one of 10 participating U.S. hospitals in 9 states between September 2020 and May 2023 with a suspected opioid overdose and had waste serum available after routine laboratory testing. Clinical data is collected from the medical record and patient serum is sent for comprehensive toxicologic analysis via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect the presence of over 1200 substances including illicit opioids, novel synthetic opioids, medications, and adulterants. Logistic multivariable regression was performed to examine the association between demographic, behavioral, and serum toxicology data with risk factors and HIV status., Results: Among the total cohort (n=1690), 1062 cases had known HIV status (62.8 % of total sample). Among patients with a known HIV status, 60 (5.6 % [95 % CI: 4.2 %, 7.0 %]) were HIV positive. Patients with HIV reported stimulant use more frequently (13.3 %) than those without HIV (6.8 %; p=0.003). After controlling for confounding, bipolar psychiatric history was a significant independent predictor of HIV positivity (aOR: 1.08; 95 % CI: 1.02, 1.13) in this population., Conclusions: In this large multicenter cohort, the prevalence of HIV for ED patients with illicit opioid overdose was 9 times higher than that expected by the general population. Bipolar disorder appears to be a novel risk factor for HIV positivity in this patient population., Competing Interests: Declaration of Competing Interest There are no financial, litigational, or other conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Epiphora in pediatrics is commonly treated with silicone nasolacrimal stents. The most common treatment duration is 3 months, but tubes are often unintentionally removed earlier and are still effective. There is no consensus on how long tubes need to be in situ and what factors influence treatment success., Methods: A retrospective chart review of patients who underwent Crawford tube placement over a 10-year period (2009-2019) was conducted. Patients were age <18 years and had Crawford tubes placed in conjunction with an otolaryngologist, who performed nasal endoscopy for direct visualization when retrieving Crawford tubes and infracture of the inferior turbinate. Bicanalicular intubation was attempted in all cases; if not possible, monocanalicular intubation was performed., Results: Forty-two patients were included in this study, representing 50 eyes. Spontaneous extrusion of tubes occurred in 54% of eyes. Tubes remained in situ for an average of 17.1 weeks (0-113 weeks). Symptoms resolved in 86% of patients, similar to procedures without endoscopy. There were no intraoperative complications. There was no association between the rate of persistent symptoms and duration of treatment., Conclusion: Nasolacrimal duct intubation using Crawford tubes performed under direct endoscopic visualization is consistently successful for the treatment of epiphora. Although epiphora can be self-resolving, persistent symptoms typically lasting past the first year of birth, warrant treatment. Children who receive Crawford tubes for epiphora commonly have spontaneous tube extrusion before treatment duration is complete. However, treatment success was not related to the length of time the tubes were in situ. Endoscopic visualization can help prevent intraoperative complications., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was to evaluate the incidence of brachial plexus injury (BPI) after single-fraction stereotactic body radiation therapy (SBRT) to apical lung tumors., Methods and Materials: A retrospective cohort analysis was performed of all patients treated with single-fraction lung SBRT at our institution from 2007 to 2022. Apical tumors were identified as those with an epicenter located above the arch of the aorta. Dosimetric analysis of dose to the brachial plexus (BP) was done using both the subclavian vessel (SCV) surrogate structure and anatomic BP. BPI was assessed per Common Terminology Criteria for Adverse Events, version 4.0, as regional paresthesia, marked discomfort and muscle weakness, and limited movement of the arm or hand., Results: A total of 45 patients met inclusion criteria with median follow-up of 21 months. There were 9 patients who exceeded the BP dose constraint using the SCV or anatomic BP volume. Only 1 patient (2.2%) developed grade 2 BPI, occurring 7 months after SBRT. Dose to the anatomic BP for the affected patient was 26.39 Gy. For the entire cohort, the median SCV and anatomic maximum BP doses were 8.44 and 7.14 Gy, respectively., Conclusions: There is considerable variability in dose delivered to the BP after SBRT to apical lung tumors. BPI after single-fraction SBRT to apical tumors is rare and rates are comparable with those reported with multifraction regimens., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Existing real-time reverse transcriptase PCR (RT-qPCR) has certain limitations for the point-of-care detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since it requires sophisticated instruments, reagents and skilled laboratory personnel. In this study, we evaluated an assay termed the reverse transcriptase-polymerase spiral reaction (RT-PSR) for rapid and visual detection of SARS-CoV-2., Methods: The RT-PSR assay was optimized using RdRp gene and evaluated for the detection of SARS-CoV-2. The time of 60min and a temperature of 63°C was optimized for targeting the RNA-dependent RNA polymerase gene of SARS-CoV-2. The sensitivity of the assay was evaluated by diluting the in-vitro transcribed RNA, which amplifies as low as ten copies., Results: The specific primers designed for this assay showed 100% specificity and did not react when tested with other lung infection-causing viruses and bacteria. The optimized assay was validated with 190 clinical samples in two phases, using automated RTPCR based TrueNat test, and the results were comparable., Conclusions: The RT-PSR assay can be considered for rapid and sensitive detection of SARS-CoV-2, particularly in resource-limited settings. To our knowledge, there is as yet no RT-PSR-based kit developed for SARS-CoV-2., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The use of rotational atherectomy (RA) in percutaneous coronary intervention (PCI) of acute coronary syndrome (ACS) is considered relatively contraindicated. There have been several observational studies showing RA use in ACS, however, no systemic studies have been undertaken. We sought to evaluate the feasibility and outcomes of RA PCI in ACS by performing a meta-analysis., Methods: We searched PUBMED, EMBASE, CINAHL, and Cochrane Central Register of Clinical Trials for any studies that evaluated the role of RA PCI in ACS. The outcomes analyzed were all-cause mortality, cardiac mortality, short and long-term major adverse cardiac events (MACE), procedural complications and cardiac perforations., Results: There was a total of 8 retrospective studies with a total population of 1237 with a median follow up of 23 months. The median age of the included patient was 73. Angiographic success rate was 97.4%. The rate of all-cause mortality and cardiac mortality were 5% (range 1-12%, p < 0.001, I 2 = 92%) and 2% (range 0-5%, P = 0.03, I 2 = 58%) respectively. In-hospital MACE and long-term MACE were 7% (range 3-13%, p < 0.001, I 2 = 87%) and 29% (range 21-37%, p = 0.21, I 2 = 34%) respectively. The incidence of total procedural complications was noted to be 7% (range 2-14%, p < 0.001, I 2 = 90%). Rate of perforation was 1% (range 0-1%, p = 0.9, I 2 = 0%)., Conclusion: Our results show that RA PCI is feasible in ACS with comparable procedural complications and short-term MACE, but with a higher long-term MACE rate compared to RA PCI in routine cases., Competing Interests: Declaration of competing interest 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., (Copyright © 2022. Published by Elsevier Inc.)

Hypertension (HTN) is a leading modifiable risk factor for multiple diseases. It has reached epidemic proportions, affecting nearly a third of the world's population. With such a high prevalence and an exhaustive list of potential complications, antihypertensive therapy has been a subject of focus for the scientific community for a long time. Recently, Dietary fiber is emerging as yet another promising candidate addressing this issue. It is a well-known fact that dietary modification alone can significantly impact a patient's health, with a noticeable effect on BP as well. But simply switching to healthy alternatives is not enough and must happen in tandem with dietary supplementation. The consumption of ultra-processed food has only increased in recent times. Hence, we feel the need to focus on dietary interventions in managing hypertension. This review aims to bring to light the current literature on the pathophysiology, risk factors, and treatment protocols of hypertension, focusing on dietary fibers and their role in hypertension management., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: The impact of behavioural risk factors on the metabolic syndrome has not been well understood by the researchers. This information is important to the policymakers for developing effective strategies and implement relevant policies or programs. Hence, we undertook this meta-analysis to estimate the effect of behavioural risk factors on the burden of metabolic syndrome., Data Synthesis: We conducted a search in the databases, such as PubMed Central, EMBASE, MEDLINE, and Cochrane library, and search engines, such as ScienceDirect and Google Scholar, from inception until March 2021. We used the Newcastle-Ottawa Scale (NOS) to assess the quality of published studies. We carried out a meta-analysis with random-effects model and reported pooled odds ratio (OR) with 95% confidence interval (CI). In total, we analysed 30 studies with 41,090 participants. The majority of the studies had good to satisfactory quality as per NOS. Physical activity had a statistically significant association with the prevalence of metabolic syndrome (pooled OR = 1.57; 95%CI: 1.28 to 1.93, I 2  = 91%). However, smoking (pooled OR = 0.96; 95%CI: 0.75 to 1.23, I 2  = 90.5%) and alcohol (pooled OR = 1.00; 95%CI: 0.75 to 1.33, I 2  = 90.8%) did not reveal a statistically significant association with the burden of metabolic syndrome., Conclusion: Physical inactivity was found to be a significant risk factor for metabolic syndrome. Given the evidence, it is important that the clinicians and policymakers are alike to recommend regular physical activity among the patients and general population., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

This report summarizes the proceedings for Day 3 of the workshop titled "Current State and Future Expectations of Translational Modeling Strategies toSupportDrug Product Development, Manufacturing Changes and Controls". From a drug product quality perspective, patient-centric product development necessitates the development of clinically relevant drug product specifications (CRDPS). In this regard, Physiologically Based Biopharmaceutics modeling (PBBM) is a viable tool to establish links between in-vitro to in-vivo data, and support with establishing CRDPS. The theme of day 3 was practical applications of PBBM to support drug product quality. In this manuscript, case studies from US FDA, EMA and pharmaceutical industry on applications of PBBM in drug product quality are summarized which include 1) regulatory agency's perspectives on establishing the safe space and achieving study waivers, 2) model-informed risk assessment on the effects of acid reducing agents, bridging of dissolution methods, food effect, and formulation selection, and 3) understanding clinical formulation performance. Breakout session discussions focused on four topics - 1) terminologies related to physiologically based modeling in support of drug product quality, 2) regulatory harmonization on evidentiary standards, 3) CRDPS approaches and 4) bridging between biorelevant and quality control (QC) dissolution methods., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Varus malalignment in total hip arthroplasty has been associated with poor long-term outcomes and complications including abnormal load distribution, endosteal osteolysis, frank loosening, and periprosthetic fractures. Postoperative radiographic assessment was performed on 224 patients from our case series who underwent cemented Exeter total hip arthroplasty using the direct lateral approach alone. No patient had a true varus-aligned stem (ie, ≤-5° on the coronal assessment). We describe our surgical technique, with 4 easily reproducible technical tips to achieve positional consistency of the femoral stem: commencing stem insertion from the piriform fossa entry point, using a femoral stem distal centralizer, aiming the tip of the component to the center of the patella, and placing the thumb between the calcar and inferior neck of the femoral component to prevent the stem from tipping into varus., (© 2020 The Authors.)

The pressing need for new pest control products with novel modes of action has spawned interest in small molecules and peptides targeting arthropod GPCRs. Genome sequence data and tools for reverse genetics have enabled the prediction and characterization of GPCRs from many invertebrates. We review recent work to identify, characterize and de-orphanize arthropod GPCRs, with a focus on studies that reveal exciting new functional roles for these receptors, including the regulation of metabolic resistance. We explore the potential for insecticides targeting Class A biogenic amine-binding and peptide-binding receptors, and consider the innovation required to generate pest-selective leads for development, within the context of new PCR-targeting products to control arthropod vectors of disease., (Copyright © 2018. Published by Elsevier Inc.)

Background: Negative psychological symptoms may impact cardiovascular (CV) risk factors such as obesity and abnormal blood pressure (BP). Currently, a third of the US population is obese (BMI ≥ 30 kg/m 2 ) and nearly half have high BP (BP > 120/80 mmHg). This research aims to investigate whether self-reported depressive symptoms in adolescence affect adulthood obesity and high BP., Methods: We leveraged the data from a representative sample of US individuals collected by the National Longitudinal Study of Adolescent to Adult Health (Add Health). We identified the survey questions pertaining to self-reported depressive symptoms in over 14,000 adolescents. Based on their follow-up health test in adulthood, we evaluated the impact of adolescent depressive symptoms on adulthood obesity and high BP by adjusting for socio-demographic, socio-economic and adolescent health status., Results: This study reveals a high prevalence of obesity (36%) and high BP (66%) among young US adults with an average age of only 28 years. Excessive moodiness in adolescence significantly impacted the development of obesity in early adulthood (p-value <0.001). 'Feeling sad' on most days in adolescence significantly increases the risk of obesity (p-value 0.01) and high BP (p-value <0.03) in early adulthood., Conclusions: This study demonstrates self-reported moodiness in adolescence to be a significant predictor of obesity in adulthood. Feeling sad on most days increase the subsequent risk for high BP. Early intervention may improve lifestyle and CV outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Transradial access (TRA) is preferred for coronary angiography (CA) or percutaneous coronary intervention due to reduced access-related complications, and mortality especially for patients with ST elevation myocardial infarction. Radial artery occlusion (RAO) is a known complication of TRA, and precludes its use as a future access site, conduit for coronary artery bypass grafting or for hemodialysis fistula placement. Although a standard dose (SD) heparin of 5000 Units is used during TRA, the risks of RAO and hematoma compared to lower dose (LD) remain unclear. To compare the risks of RAO and hematoma using SD vs. LD heparin after CA through TRA, we performed a meta-analysis of randomized controlled trials (RCT)., Methods: We searched PubMed, EMBASE, CINAHL and CENTRAL for RCTs since inception through 06/30/2017 and used random effects model for analysis. The outcomes analyzed were RAO, hematoma formation and radial artery compression time (RACT)., Results: We identified a total of 6 RCTs with a total of 2239 patients. SD heparin resulted in a trend toward a lower risk of RAO [4.2% vs. 10.7%; risk ratio (RR): 0.40, 95% confidence interval (CI): 0.16-1.0; P=0.05], a trend toward increased risk of hematoma [2.2% vs. 1.1%; 1.83 (0.91-3.66); P=0.09], and a longer duration of RACT [mean difference: 9.64min (4.01-15.28); P=0.0008] compared to LD., Conclusions: The current meta-analysis showed a trend towards reduction in the risk of RAO with the use of standard dose heparin. Larger randomized trials should explore the appropriate dosing of heparin to prevent radial artery occlusion., (Published by Elsevier Inc.)

Objectives: To compare the efficacy and safety of manual compression (MC) with vascular hemostasis devices (VHD) in patients undergoing coronary angiography (CA) or percutaneous coronary intervention (PCI) through femoral artery access., Introduction: The use of femoral artery access for coronary procedures may result in access-related complications, prolonged immobility and discomfort for the patients. MC results in longer time-to-hemostasis (TTH) and time-to-ambulation (TTA) compared to VHDs but its role in access-related complications remains unclear in patients undergoing coronary procedures., Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL and relevant references for English language randomized controlled trials (RCT) from inception through September 30, 2016. We performed the meta-analysis using random effects model. The outcomes were time-to-hemostasis, time-to-ambulation, major bleeding, large hematoma >5cm, pseudoaneurysm and other adverse events., Results: The electronic database search resulted in a total of 44 RCTs with a total of 18,802 patients for analysis. MC, compared to VHD resulted in longer TTH [mean difference (MD): 11.21min; 95% confidence interval (CI) 8.13-14.29; P<0.00001] and TTA [standardized mean difference: 1.2 (0.79-1.62); P<0.00001] along with excess risk of hematoma >5cm formation [risk ratio (RR): 1.38 (1.15-1.67); P=0.0008]. MC resulted in similar risk of major bleeding [1.01 (0.64-1.60); P=0.95] pseudoaneurysm [0.99 (0.75-1.29); P=0.92], infections [0.52 (0.25-1.10); P=0.09], need of surgery [0.60 (0.29-1.22); P=0.16), AV fistula [0.93 (0.68-1.27); P=0.63] and ipsilateral leg ischemia [0.95 (0.57-1.60); P=0.86] compared to VHD., Conclusion: Manual compression increase time-to-hemostasis, time-to-ambulation and risk of hematoma formation compared vascular hemostasis devices., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To describe the presentation, clinical evaluation, work-up, surgical management, and surgical outcomes in children older than 8 years with spontaneous, comitant, acquired nonaccommodative esotropia (ANAET)., Design: Retrospective chart review., Participants: Children who underwent bilateral medial rectus recession surgery for ANAET with initial esotropia onset later than 8 years of age., Methods: The medical records of children older than 8 years presenting with ANAET from 2009 to 2015 were retrospectively reviewed. The clinical presentation, work-up, surgical intervention, preoperative and postoperative deviations, and surgical outcomes were recorded., Results: A total of 7 healthy patients were identified. The average age of onset was 11.9 years. All patients presented with symptoms of diplopia with large-angle esotropia. Most patients had no preceding illness and presented with minimal refractive error. All 7 patients had unremarkable neurological and general pediatric evaluations without findings of acute intracranial pathology on neuroimaging. Bilateral medial recession surgery was performed for all 7 patients with resolution of diplopia and excellent stereopsis postoperatively., Conclusions: Diplopia is the most common presenting symptom among older children presenting with ANAET. Bilateral medial recession surgery achieved excellent postoperative results with resolution of diplopia and excellent stereopsis., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: The "resource therapist" supervisory radiation therapy roles at the British Columbia Cancer Agency were recently evaluated., Methods: The process included interviews with resource therapists (n = 22) and an electronic survey of stakeholders including department managers (n = 5) and clinical radiation therapists (RTs) (n = 230)., Results: Themes from both sets of data included the ability and advisability of maintaining clinical expertise, role clarity and job creep, and the definition of leadership. The resource therapists were balancing an increasingly complex administrative workload that varied between provincial centres. The understanding of the role differed between stakeholders. Only 48% of the RTs agreed that they had a good idea of what resource therapists do and many desired the resource therapists to be more "hands on.", Conclusions: In agreement with the literature, many resource therapists view themselves as clinicians first and managers second. There is also a marked difference in how the role is viewed between resource therapists and RTs. Role incumbents may benefit from access to more formal preparation, including job shadowing, training, and mentoring. There is also a need to increase understanding of the role across all stakeholder groups., (Copyright © 2016 Canadian Association of Medical Radiation Technologists. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of the present study was to determine the variations in the position of the coronary sinus (CS) ostium in normal cadaveric fetal (28 weeks or more) hearts and to assess the impact that these variations had on the dimensions of the triangle of Koch (TK)., Methods: This cross-sectional analytical study was conducted on 28 fetal hearts. The dimensions and area of the TK were calculated by two methods, M1 (anatomical) and M2 (clinical). The position of the CS was defined with respect to the tendon of Todaro. Differences between M1 and M2 were estimated using the paired T test. Pearson's correlation coefficient and the adjusted correlation coefficient were used to estimate the strength of association between measurements made by the methods., Results: Ten (35.7%) cadavers were male and 18 (64.3%) female. The mean gestational age was 32.4±3.3 weeks. Using M1, the mean dimensions of the triangle in millimeters (mm) were 9.2±2.2, 6.6±1.8, and 6±2.4 respectively for a, b and c. Similarly, the dimensions using M2 were 7±2.1, 4.7±1.5, and 4.8±2.2. The area in mm 2 was 20.4±10.4 and 11.7±6.7 using M1 and M2 respectively. All measurements were significantly greater with M1. All correlation coefficients were high and significant. The CS ostium and tendon of Todaro maintained a relatively constant positional relationship., Conclusions: Significantly higher values were noted in the dimensions of TK using M1. High significant positive correlations were observed in measurements made by the two methods. The CS ostium was relatively constantly placed within the TK., (Copyright © 2016. Published by Elsevier B.V.)

Purpose: The purpose of the current study was to assess the penetrance of NRXN1 deletions., Methods: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions., Results: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P < 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3' end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5' NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035)., Conclusions: The results support the importance of exons near the 5' end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61.

To assess and evaluate the current level of ophthalmology knowledge and teaching curriculum in undergraduate year 3 (MS-3) at Western University. The Undergraduate Medical Education Curriculum at Western University has instituted additional ophthalmology lecture series to all MS-3 students. A test on basic ophthalmic knowledge was administered to MS-3 students immediately before and after lecture series to evaluate the level of knowledge at baseline and after ophthalmology didactic teaching. An evaluation survey was also given to MS-3 students to assess students' self-perceived level of competency, exposure, and interests in ophthalmology. A total of 134 students attended the ophthalmology lecture series in the study, and 88.1% of students completed the pretest, post-test, and Ophthalmology Education Survey. The average pretest and post-test scores were 40.7% and 75.6% (p < 0.01), respectively. The average rating from MS-3 students for ophthalmology exposure during medical school education was 2.11 (1 = "very minimal" and 5 = "more than adequate"). The average rating for desire for additional didactic ophthalmology lectures was 4.02 (1 = "strongly disagree" and 5 = "strongly agree"). The average rating for interest in ophthalmology was 2.74 (1 = "very little interest" and 5 = "very strong interest"). The additional ophthalmology lecture series had a positive impact on the level of ophthalmic knowledge among MS-3 students, and a strong desire for more ophthalmology teaching during medical school education was identified, as evidenced by the survey undertaken by students after the lectures., (Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

In order to promote the natural healing process, drug-functionalized nanofibrous transdermal substitute was fabricated using gellan as chief polymer and polyvinyl alcohol (PVA) as supporting polymer via electrospinning technique. These fabricated nanofibers physiochemically mimic the extracellular matrix (ECM) which supports the cell growth. For neo-tissue regeneration in a sterilized environment, amoxicillin (Amx) was entrapped within these nanofibers. Entrapment of Amx in the nanofibers was confirmed by FESEM, FTIR, XRD and TG analysis. In vitro cell culture studies revealed that the fabricated non-cytotoxic nanofibers promoted enhance cell adherence and proliferation of human keratinocytes. A preliminary in vivo study performed on rat model for full thickness skin excision wound demonstrated the prompt re-epithelialization in early phase and quicker collagen deposition in later phases of wound healing in case of Amx-functionalized gellan/PVA nanofibers. Data collectively confirmed the potential usage of gellan based electrospun nanofibers as transdermal substitute for faster skin restoration., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Angiogenesis plays important roles in tumor growth and metastasis, thus development of a novel angiogenesis inhibitor is essential for the improvement of therapeutics against cancer. Thrombospondins-1 (TSP-1) is a potent endogenous inhibitor of angiogenesis that acts through direct effects on endothelial cell migration, proliferation, survival, and activating apoptotic pathways. TSP-1 has been shown to disrupt estrogen-induced endothelial cell proliferation and migration. Here we investigated the potential of pterostilbene carboxaldehyde thiosemicarbazone (PTERC-T), a novel resveratrol (RESV) derivative, to inhibit angiogenesis induced by female sex steroids, particularly 17β-Estradiol (E2), on Human umbilical vein endothelial cells (HUVECs) and to elucidate the involvement of TSP-1 in PTERC-T action. Our results showed that PTERC-T significantly inhibited 17β-E2-stimulated proliferation of HUVECs and induced apoptosis as determined by annexin V/propidium iodide staining and cleaved caspase-3 expression. Furthermore, PTERC-T also inhibited endothelial cell migration, and invasion in chick chorioallantoic membrane (CAM) assay. In contrast, RESV failed to inhibit 17β-E2 induced HUVECs proliferation and invasion at similar dose. PTERC-T was also found to increase TSP-1 protein expression levels in a dose-dependent manner which, however, was counteracted by co-incubation with p38MAPK or JNK inhibitors, suggesting involvement of these pathways in PTERC-T action. These results suggest that the inhibitory effect of PTERC-T on 17β-E2 induced angiogenesis is associated, at least in part, with its induction of endothelial cell apoptosis and inhibition of cell migration through targeting TSP-1. Thus, PTERC-T could be considered as a potential lead compound for developing a class of new drugs targeting angiogenesis-related diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for such research should urgently be created and facilitated there., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Canadian radiation therapy departments usually have flat organizational structures, with relatively few administrative/managerial levels. The "unit supervisor" level is a typical job role that provides direct supervision of one or more treatment units with a mixture of clinical and administrative duties., Methods: At the British Columbia Cancer Agency, the unit supervisor role was recently evaluated. One approach used as part of the evaluative process was a series of telephone interviews to examine similar roles across Canada (n = 9)., Results: Data indicated that departmental administrative tasks seem to be increasing significantly, and there is a move toward the addition of more administrative "middle" roles across the country to deal with these. Unit supervisor roles are subsequently becoming less clinical, but there is an emerging tension with moving away from solely clinical responsibilities and assuming more administrative work., Conclusions: The historic unit supervisor role was part of the team and did little administrative work. This model is becoming difficult to sustain, and tensions can arise in this new environment when using old organizational models. Focused departmental clinical expertise is important; however, balancing clinical and administrative expectations within the unit supervisor role can be problematic. Role expectations need to be examined, clarified, and communicated within departments. If unit supervisor roles are deemed clinical experts, then clinical time needs to be protected for expertise to be sustained., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Monophosphoryl lipid A (MPL) and Quil A are two immunological adjuvants commonly used in vaccines. At present no simple, validated methods for the quantification of Quil A and MPL have been previously reported therefore the aim of the current study was to develop a simple, fast and validated method to quantify MPL and Quil A using high performance liquid chromatography evaporative light scattering detection (HPLC-ELSD). The HPLC-ELSD technique was carried out using a ZORBAX Eclipse XDB-C8 column (2.1×50 mm; particle size, 3.5 μm) in an isocratic elution mode at 25 °C. MPL was eluted at a retention time of 1.8 min with methanol-water as the mobile phase and a detector temperature of 75 °C. Quil A was resolved as three peaks with retention times of 4.1, 5.5 and 6.4 min with a detector temperature of 30 °C and with water-acetonitrile and 0.01% formic acid as the mobile phase. The nebulizer pressure and gain were set at 3.5 bar and 10, respectively. Calibration curves plotted for both the adjuvants had an R(2)>0.997. Accuracy, intra- and inter-day precision were within the accepted limits. The limit of detection for MPL and Quil A were calculated as 1.343 and 2.06 μg/mL, respectively. The limit of quantification was 2.445 for MPL and 8.97 μg/mL for Quil A. This analytical method was used to quantify the entrapment and in vitro release of MPL and Quil A in a poly lactic-co-glycolic acid (PLGA) nanoparticle vaccine., (Copyright © 2014 Elsevier B.V. All rights reserved.)

While prohibition has been the dominant regime of cannabis control in most countries for decades, an increasing number of countries have been implementing cannabis control reforms recently, including decriminalization or even legalization frameworks. Canada has held out from this trend, although it has among the highest cannabis use rates in the world. Cannabis use is universally criminalized, and the current (conservative) federal government has vowed not to implement any softening reforms to cannabis control. As a result of several higher court decisions, the then federal government was forced to implement a 'medical marijuana access regulations' program in 2001 to allow severely ill patients therapeutic use and access to therapeutic cannabis while shielding them from prosecution. The program's regulations and approval processes were complex and subject to extensive criticism; initial uptake was low and most medical marijuana users continued their use and supply outside the program's auspices. This year, the government introduced new 'marijuana for medical purposes regulations', which allow physicians to 'authorize' medical marijuana use for virtually any health condition for which this is considered beneficial; supply is facilitated by licensed commercial producers. It is expected that some 500,000 users, and dozens of commercial producers will soon be approved under the program, arguably constituting - as with medical marijuana schemes elsewhere, e.g. in California--de facto 'legalization'. We discuss the question whether the evolving scope and realities of 'medical cannabis' provisions in Canada offer a 'sneaky side door' or a 'better third way' to cannabis control reform, and what the potential wider implications are of these developments., (Copyright © 2014. Published by Elsevier B.V.)

Some drug discovery approaches can benefit from restricting the access of compounds to the central nervous system (CNS) to minimise the risk of side-effects. Designing compounds that act as substrates for efflux transporters in the blood–brain barrier can achieve CNS restriction without significantly impairing absorption in the intestine. In vitro assays can be deployed to optimise a balance between passive permeability and active efflux via the ABC family transporters P-glycoprotein (P-gp, ABCB1) and Breast Cancer Resistance Protein (BCRP, ABCG2) whilst in vivo estimates of distribution of unbound concentrations of drug are needed to understand pharmacologically relevant exposure in peripheral and central compartments. This strategy can deliver significant CNS restriction whilst retaining good oral bioavailability, cell penetration and pharmacological activity. The possible risks of targeting P-gp and BCRP in orally delivered drugs are discussed.

Continuing professional development (CPD) is essential to maintaining a knowledgeable health care work force. Studies of many health care professionals link CPD to competence, motivation, and job satisfaction. There is little information about CPD in the field of radiation therapy. In addition, staff views on CPD have been well researched, but there is a lack of literature looking at the opinions of managers. This study examined the following questions: (1) Is there a disparity between the views of radiation therapists and their managers concerning support for continuing professional development? (2) Where does the responsibility for continuing professional development lie? (3) Are radiation therapists aware of the availability of support within their department? and (4) Is there a difference between the academic (university affiliated) versus nonacademic centres? A self-administered electronic questionnaire was sent to 14 Ontario cancer centres. Of the 700 radiation therapists surveyed, there were 161 completed e-mail replies, giving a total response rate of approximately 23%. The final number of respondents in the management category was 25. Results showed that although more radiation therapists than managers felt that the organization should be responsible for providing opportunities for CPD, more managers than radiation therapists felt that the organization did indeed provide time off to support CPD. An additional discovery in the area of organizational responsibility is that, although the nonmanagement staff results were similar in both the academic and nonacademic settings, the management results differed significantly. Conclusions and recommendations indicate the need to expand the definition of CPD, implement more transparent CPD policies and application processes, increase communication between managers and staff, and investigate the need for radiation therapist-specific research on clinical competence., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Idiopathic intracranial hypertension (IIH) in children is an uncommon but significant cause of morbidity, including permanent visual loss. It is important to understand if, like obesity, IIH in children is on the rise and is related to that increase. The aim of this study is to compare the recent incidence rate of pediatric IIH in a tertiary care hospital with earlier data published from that same hospital., Design: Retrospective chart review., Participants: All children aged 2 to 16 years diagnosed with IIH at the IWK Health Centre in Halifax between 1997 and 2007., Methods: Charts of eligible patients were reviewed to ensure all diagnostic criteria for IIH were met. Incidence and obesity rates were calculated based on data from Statistics Canada., Results: Twelve cases (5 males, 7 females) fulfilling the diagnostic criteria for IIH were identified, for an annual incidence of 0.6 cases per 100,000 children with no sex predilection (p = 0.51). Obesity was noted in 75% of patients examined (9/12). Children older than 12 years were more likely to be obese (6/6, 100%) compared with those younger than 12 years (3/6, 50%)., Conclusions: The calculated incidence is lower than that found in an earlier study for the same geographic region (0.9 cases per 100,000 children) despite increasing obesity rates. This decrease may be a reflection of improved diagnostic techniques or may indicate that factors other than obesity govern IIH predilection in younger children., (© 2013 Canadian Ophthalmological Society Published by Canadian Ophthalmological Society All rights reserved.)

Tissue engineered heart valves (TEHVs) may provide a permanent solution to congenital heart valve disease by permitting somatic valve growth in the pediatric patient. However, to date, TEHV studies have focused primarily on collagen, the dominant component of valve extracellular matrix (ECM). Temporal decreases in other ECM components, such as the glycosaminoglycans (GAGs), generally decrease as cells produce more collagen under mechanically loaded states; nevertheless, GAGs represent a key component of the valve ECM, providing structural stability and hydration to the leaflets. In an effort to retain GAGs within the engineered constructs, here we investigated the utility of the protein fibrin in combination with a valve-like, cyclic flexure and steady flow (flex-flow) mechanical conditioning culture process using adult human periodontal ligament cells (PLCs). We found both fibrin and flex-flow mechanical components to be independently significant (p<0.05), and hence important in influencing the DNA, GAG and collagen contents of the engineered tissues. In addition, the interaction of fibrin with flex-flow was found to be significant in the case of collagen; specifically, the combination of these environments promoted PLC collagen production resulting in a significant difference compared to dynamic and statically cultured specimens without fibrin. Histological examination revealed that the GAGs were retained by fibrin entrapment and adhesion, which were subsequently confirmed by additional experiments on native valve tissues. We conclude that fibrin in the flex-flow culture of engineered heart valve tissues: (i) augments PLC-derived collagen production; and (ii) enhances retention of GAGs within the developing ECM., (Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine whether surgery to correct decompensated exotropia in adulthood had an impact on common visually guided manual tasks in the postoperative period., Design: Case report., Participants: Three adult patients with long-standing strabismus., Methods: Three adult patients took part in a series of preoperative and postoperative binocular and monocular reaching and grasping tasks before and after undergoing strabismus surgery. Tasks were designed to examine normal goal-directed actions (reaching to visual targets, grasping blocks) and to highlight differences between binocular and monocular control of action (grasping visible object in dark environment)., Results: A consistent pattern of change was not found in the 6- to 12-month postoperative period with the tasks provided., Conclusions: Surgery in adulthood to correct strabismus may not have a significant impact on the control of visually guided actions, at least in the first 6 to 12 months after surgery. Possibly, compensatory strategies used throughout their development (e.g., monocular cues) may continue to be used in the initial period postoperative period. More subjects and longer study period are recommended to make a definitive conclusion., (Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

The heat shock protein 70 (Hsp70) family of molecular chaperones has important functions in maintaining proteostasis under stress conditions. Several Hsp70 isoforms, especially Hsp72 (HSPA1A), are dramatically upregulated in response to stress; however, it is unclear whether these family members have biochemical properties that are specifically adapted to these scenarios. The redox-active compound, methylene blue (MB), has been shown to inhibit the ATPase activity of Hsp72 in vitro, and it promotes degradation of the Hsp72 substrate, tau, in cellular and animal models. Here, we report that MB irreversibly inactivates Hsp72 but not the nearly identical, constitutively expressed isoform, heat shock cognate 70 (Hsc70; HSPA8). Mass spectrometry results show that MB oxidizes Cys306, which is not conserved in Hsc70. Molecular models suggested that oxidation of Cys306 exposes Cys267 to modification and that both events contribute to loss of ATP binding in response to MB. Consistent with this model, mutating Cys267 and Cys306 to serine made Hsp72 largely resistant to MB in vitro, and overexpression of the C306S mutant blocked MB-mediated loss of tau in a cellular model. Furthermore, mutating Cys267 and Cys306 to the pseudo-oxidation mimic, aspartic acid, mirrored MB treatment: the C267D and C306D mutants had reduced ATPase activity in vitro, and overexpression of the C267/306D double mutant significantly reduced tau levels in cells. Together, these results suggest that redox sensing by specific cysteine residues in Hsp72, but not Hsc70, may be an important component of the chaperone response to oxidative stress., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Study Objective: To assess the performance and cervical (C)-spine movement associated with laryngoscopy using the Bullard laryngoscope (BL), GlideScope videolaryngoscope (GVL), Viewmax, and Macintosh laryngoscopes during conditions of a) unrestricted and b) restricted C-spine and temporomandibular joint (TMJ) mobility., Design: Prospective, controlled, randomized, crossover study., Setting: University teaching hospital., Subjects: 21 cadavers with intact C-spine anatomy., Interventions: Each cadaver underwent to total of 8 intubation attempts to complete the intubation protocol using all four devices under unrestricted and restricted C-spine and TMJ mobility., Measurements: Laryngoscopic view was graded using the modified Cormack-Lehane system. Time to best laryngoscopic view and total time to intubation were recorded. C-spine movement was measured between McGregor's line and each vertebra from radiographs taken at baseline and at best laryngoscopic view., Main Results: During both intubating conditions, the BL achieved the highest number of modified Cormack-Lehane grade 1 and 2A laryngoscopic views as compared to the other three devices (P < 0.05) and had fewer intubation failures than the Viewmax or Macintosh laryngoscopes (P < 0.05). The GVL had superior laryngoscopic performance as compared to the Viewmax and Macintosh laryngoscopes (P < 0.05) and had fewer intubation failures than those two devices (P < 0.05). All devices except the Macintosh laryngoscope in restricted mobility achieved median times to intubation in less than 30 seconds. For both conditions, BL showed the least total absolute movement between Occiput/C1 and C3/C4 of all the devices (all P < 0.05). Most of the difference was seen at C1/C2., Conclusions: In cadavers with unrestricted and restricted C-spine mobility, the BL provided superior laryngoscopic views, comparable intubating times, and less C-spine movement than the GVL, Viewmax, or Macintosh laryngoscopes., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Drosophila nemo (nmo) and other Nemo-like kinase family members (Nlks) are well-established key regulators of numerous conserved signaling pathways, such as Wg and BMP. nmo mutants display pleiotropic defects at different developmental stages, including the embryo. In this study we describe a detailed characterization of embryonic cuticle patterning defects associated with maternal loss of nmo. nmo mutant embryos consistently show segmentation defects, most frequently fusions of pairs of denticle belts in alternating segments. These phenotypes are reminiscent of those associated with defects in pair-rule patterning. Genetic interaction studies demonstrate that Nmo promotes Even-skipped (Eve) activity and is required to promote the expression of the Eve target, engrailed (en), in even numbered parasegments. We find that Nmo regulates a subset of Eve activities by stimulating Eve-mediated suppression of the odd-skipped (odd) repressor. Furthermore, we isolate Nmo in a protein complex with Eve and show that Nmo phosphorylates Eve in in vitro kinase assays. These studies reveal a novel role for the Nmo kinase in embryonic pattern formation through its regulation of the homeodomain-containing transcription factor Eve., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: Oral acetazolamide is a potent medical treatment for pediatric glaucoma, but ophthalmologists may have concerns that it retards weight gain in children and may choose surgical management instead., Design: Retrospective chart review., Participants: Twenty-two well children with glaucoma taking acetazolamide orally for >or=3 months., Methods: Abnormal weight gain was determined using downward crossing of 2 percentile lines on growth charts and change in z score for weight using a hierarchical linear model., Results: One patient with Sturge-Weber syndrome and growth failure was excluded when growth hormone deficiency was diagnosed. Two patients crossed 2 lines downward; both showed metabolic acidosis. The trend for the 2 reversed after medication was discontinued. The other 20 tracked steadily on growth curves. Eleven patients (11/22, 50%) showed a decline in z score for weight over the follow-up period, and the remainder showed an increase, for an overall estimate of slope in this sample of 0.01, which was not significant (p = 0.8)., Conclusions: Oral acetazolamide may cause poor weight gain in a small subset of children on treatment. Metabolic acidosis may be a mediating factor for growth failure. Our data suggest that acetazolamide does not cause significant weight changes in cases of pediatric glaucoma. Growth parameters should be followed. Growth hormone deficiency should be considered in Sturge-Weber syndrome. Prospective study is needed.

Objective: The purpose of this study was to determine the rate and course of blebitis/late endophthalmitis 5-10 years post-filtration surgery and to evaluate risk factors., Design: Retrospective chart review., Participants: Three hundred fifty consecutive patients undergoing filtration surgery from January 1, 1996, to December 31, 2001, by a single surgeon. Five hundred twenty-one surgeries were evaluated., Methods: Data recorded included patient demographics, systemic disease(s), glaucoma type, left or right eye, date of surgery, last follow-up date, surgical procedure details, postoperative antimetabolite injections, bleb manipulations, bleb leaks and treatment, date of infection, type of infection, pre- and postinfection visual acuity, intraocular pressure (preinfection, during, and postinfection), treatment, and functionality of the bleb after infection. Statistical analysis used for assessment of risk factors included Fisher's exact test and the Student's t test analysis., Results: There were a total of 5 bleb-related infections (0.96%), 4 blebitis and 1 endophthalmitis, occurring at a mean of 31.3 months after surgery. Three occurred in blacks and 2 in Caucasians. The mean age at surgery for the infected group was 53.5 years compared with 64.7 years for those with no infection. Mitomycin C was used in 4 of the 5 cases compared with in 52% of controls. Four underwent suture lysis. Bleb leaks occurred in 4 cases. The bleb remained functional and vision unchanged in the 4 blebitis cases; however, the endophthalmitis case lost vision and had uncontrolled pressure following the infection., Conclusions: We report a 0.96% bleb infection rate with a 5.3-year mean follow-up. Bleb leak, black race, and bleb manipulation were risk factors for infection.