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Age is an important risk factor of stroke, cognitive decline, and dementia. Senescent endothelial cells (ECs) accumulate with advancing age through exposure to cellular stress, such as that exerted by hypertension and diabetes. These senescent ECs have altered characteristics, such as altered tight junction proteins, use of a more indiscriminate transcellular transport system, increased inflammation, and increased immune cell interactions. ECs are the main component of the blood-brain barrier (BBB), separating the brain from systemic circulation. As senescent ECs accumulate in the BBB, their altered functioning results in the disruption of the barrier. They have inadequate barrier-forming properties, disrupted extracellular matrix, and increased transcytosis, resulting in an overly permeable barrier. This disruption of the BBB can have important effects in stroke and cognitive impairment, as presented in this review. Besides increasing the permeability of the BBB, senescent ECs can also impair angiogenesis and vascular remodeling, which in ischemic stroke may increase risk of hemorrhagic transformation and worsen outcomes. Senescent ECs may also contribute to microvascular dysfunction, with disruption of cerebral perfusion and autoregulation. These may contribute to vascular cognitive impairment along with increased permeability. With an aging population, there is growing interest in targeting senescence. Several ongoing trials have been evaluating whether senolytics can slow aging, improve vascular health, and reduce the risk of stroke and cognitive decline.

Background: Altered vaccine demands and uneven utilization patterns in childhood immunization are evident nationwide. These variabilities may stem from a range of internal and external factors influencing parental preferences. Regular checks and balances are necessary to ensure equal accessibility for all sections of society., Aim: To assess the usage trends of childhood vaccines for 5 years (2018-2022) and to monitor instances of delayed/incomplete immunization status within the community., Methodology: This study recorded the utilization trends of all recommended childhood vaccines over a 5-year period using an ambispective design. The immunization details from 3 years (2018, 2019 and 2020) were retrieved retrospectively, while those from 2 years (2021-2022) were collected prospectively through the immunization registry. Trends in childhood vaccine utilization were recorded across different years, and delays and incomplete vaccine utilization among children, along with factors resulting in deviated immunization timelines, were analysed and compared. The association of factors with deviated immunization utilization was determined using the chi-square test, and a two-way ANOVA analysed utilization variabilities over 5 years., Result: Overall, the study profiled 32,085 children's (who utilized 87,782 vaccine doses) vaccine utilization pattern for 5 years. Optional vaccines were less utilized (18.12% doses by 25.14% children) compared to mandatory vaccines (81.88% doses utilized by 74.86%). The most utilized mandatory vaccine was oral polio (17.48%) and for optional vaccines, it was measles mumps rubella (MMR; 28.31%). Boys had the highest utilization (55.97%) with a significant male preponderance in optional vaccine utilization ( p value <0.05). Overall, there was a 26.12% decline (percent change) in vaccine utilization in 2022 compared to 2018. Among children with delayed immunization timelines (6.02%), 3.38% were on catch-up, and 2.45% were not. The most commonly delayed vaccines were diphtheria + tetanus + pertussis boosters (30.90%), Tdap (26.19%) and MMR vaccines (20.65%). Influenza vaccines (28.08%) were the most partially utilized optional vaccine, followed by varicella vaccines (20.92%). Factors such as gender (female), age over 1 year, rural residence and low- to middle-income families were significant predictors of deviated immunization status in children., Conclusion: The study mapped the utilization trends of immunizations at a tertiary care hospital in south India over the past 5 years, including the COVID-19 years. Gender inequality in the utilization of optional vaccines is a concern that warrants further research and redressal. Timely administration of childhood vaccinations is crucial for reducing susceptibility to vaccine-preventable diseases and promoting overall well-being., (© The Author(s), 2024.)

Population studies have suggested that viral infections may be contributing to risk of ischemic stroke, although the mechanisms for this are unclear. In this review, we examine the epidemiological evidence supporting the involvement of viral diseases, including influenza, COVID-19, chronic herpesvirus infections, and hepatitis C in current trends of stroke incidence. To support these associations, we highlight the virus-host interactions that are critical in the context of stroke, including direct effects of acute and persistent viral infections on vascular function, inflammation, and thrombosis. Additionally, we evaluate the systemic changes that occur during viral infection that can predispose individuals to ischemic stroke, including alterations in blood pressure regulation, coagulation, and lipid metabolism. Our review emphasizes the need to further elucidate precise mechanisms involved in viral infections and stroke risk. Future research will inform the development of targeted interventions for stroke prevention in the context of viral diseases.

The goal of this research was to study the effect of different doses of resveratrol (RS) and RS with donepezil (DPZ) on the deposition of amyloid beta (Aβ) and neurofibrillary tangles (NFTs) in colchicine-induced Alzheimer's disease (AD) brain. The study included three months old male Albino  Wistar  rats and consisted of six animal groups: AD model (group 1), treatment groups, RS 10 mg/kg body weight (group 2), RS 20 mg/kg body weight (group 3), RS 10 mg/kg body weight along with DPZ 1 mg/kg body weight (group 6), prophylaxis groups, RS 10 mg/kg body weight (group 4) and RS 20 mg/kg body weight (group 5). In the treatment groups, RS was given for 7 consecutive days from the day of induction of AD, and in the prophylaxis groups, we started RS 7 days even before the induction of AD and continued for seven days after the induction. The number of Aβs and NFTs at the frontal region, cornu ammonis (CA) 1,2,3,4 and dentate gyrus regions of hippocampus were evaluated. The immunohistochemical analysis was performed by using mouse anti-β-amyloid antibody for the Aβ plaques and polyclonal rabbit anti-human tau for the tau-positive neurons. The present study observed the accumulation of Aβ plaques and tau-positive neurons in the AD model. However, their numbers were significantly decreased in the treatment groups ( p  < 0.001). The best results were observed when RS 10 mg was given prophylactically ( p  < 0.01) and RS along with DPZ ( p  < 0.001), suggesting the neuroprotective effect of RS and its synergistic effect with the DPZ., Competing Interests: Conflict of interestThe authors of this manuscript declare that there are no conflicts of interest associated with this manuscript., (© The Author(s) 2024.)

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid protein in the walls of cerebral blood vessels. This deposition of amyloid causes damage to the cerebral vasculature, resulting in blood-brain barrier disruption, cerebral hemorrhage, cognitive decline, and dementia. The role of the immune system in CAA is complex and not fully understood. While the immune system has a clear role in the rare inflammatory variants of CAA (CAA related inflammation and Abeta related angiitis), the more common variants of CAA also have immune system involvement. In a protective role, immune cells may facilitate the clearance of beta-amyloid from the cerebral vasculature. The immune system can also contribute to CAA pathology, promoting vascular injury, blood-brain barrier breakdown, inflammation, and progression of CAA. In this review, we summarize the role of the immune system in CAA, including the potential of immune based treatment strategies to slow vascular disease in CAA and associated cognitive impairment, white matter disease progression, and reduce the risk of cerebral hemorrhage. HIGHLIGHTS: The immune system has a role in cerebral amyloid angiopathy (CAA) which is summarized in this review. There is an inflammatory response to beta-amyloid that may contribute to brain injury and cognitive impairment. Immune cells may facilitate the clearance of beta-amyloid from the cerebral vasculature. Improved understanding of the immune system in CAA may afford novel treatment to improve outcomes in patients with CAA., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: This study aimed to investigate the effect of spatial adjacencies on nurses' walking patterns and the subsequent impact on staff satisfaction with perceived accessibility and adjacency-related issues., Background: Recognizing the crucial importance of spatial adjacencies in healthcare facilities is essential, as they significantly affect staff morale, fatigue management, operational efficiency, error reduction, and overall patient care excellence, highlighting the need for objective assessments to evaluate the impact of facility layout and space configuration on workflow patterns and staff satisfaction in patient care units., Methods: Integrating on-site observations with survey data, we explored how spatial adjacencies affect staff walking behavior and satisfaction in two med-surgical unit floors., Results: The findings highlighted a significant frequency of movements between nurse stations, patient rooms, and medication areas. Regression analysis identified several contributing factors to staff satisfaction, including the proximity of supplies, team visibility, ease of access across departments, and the location of equipment rooms. Specifically, satisfaction with the proximity of supplies was positively associated with increased provider satisfaction with workflow, quality of care, and workplace. Additionally, valuable feedback from staff revealed concerns regarding break room placement, medication area functionality, and disparities in the availability of supplies., Conclusion: This study highlighted the critical need for carefully planned spatial adjacency strategies to enhance workflow efficiency and raise clinical staff satisfaction within healthcare facilities. The actionable insights gleaned from this research offer valuable direction to architects, healthcare administrators, and design professionals, enabling the creation of environments that positively resonate with healthcare providers and improve healthcare operations., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Quality measurement as part of quality improvement in healthcare is integral for service delivery and development. This is particularly pertinent for health services that deliver care in ways that differ from traditional practice. Community Emergency Medicine (CEM) is a novel and evolving concept of care delivered by services in parts of the UK and Ireland. This scoping review aims to provide a broad overview of how quality may be measured within services delivering CEM., Methods and Analysis: The methodology follows both the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR). It is guided by recognised work of Arksey and O'Malley and the guidelines developed by the Joanna Briggs Institute. Several databases will be searched: MEDLINE, EMbase, EMcare, CINAHL, Scopus, the Cochrane Library and grey literature. Search terms have been developed by representatives within Community Emergency Medicine services. Two reviewers will independently screen eligible studies for final study selection. Results will be collected and analysed in descriptive and tabular form to illustrate the breadth of quality indicators that may be applicable to CEM services. This scoping review protocol has been registered with the Open Science Framework platform (osf.io/e7qxg)., Discussion: This is the first stage of a larger research study aimed at developing national quality indicators for CEM. The purpose of this scoping review is to provide a comprehensive review of quality indicators that could be used within CEM. The results will be mapped using a framework and identify gaps in the literature to help guide future-focused research., (© 2023. The Author(s).)

As the facial transplantation procedures are becoming more popular and frequent in recent years, for repairing facial trauma, variations in the veins of head and neck needs to be reported time and again. This study was undertaken to examine the course and drainage pattern of the facial vein and external jugular vein on this context and emphasize its surgical implications. The authors studied the head and neck region of 50 embalmed cadavers of both sexes to document normal and variant anatomy of facial, retromandibular, and external jugular veins. In 30% of the head and neck regions, different draining pattern of the above-mentioned veins were observed. One of the rare variation discovered was the splitting of the retromandibular vein to embrace the external carotid artery within the parotid gland. The data about variations in the termination of facial vein, retromandibular vein, and external jugular vein, as observed in the present study might be useful in avoiding accidental injury to these vessels during any surgical intervention in the face as well as neck. Level of Evidence: IV., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Objective: This exploratory study examines a rural critical access hospital (CAH) staff's perception of current obstacles and needs concerning the physical environment., Background: CAH intends to improve access to healthcare, coordinate with experts and providers, and serve as the rural population's healthcare hub. It is imperative to understand environmental qualities that impact the quality of care to develop effective policies and design guidelines for rural healthcare. Nevertheless, a limited number of studies have focused on user or organizational outcomes related to the physical environment of rural healthcare settings., Methods: This cross-sectional exploratory qualitative case study was conducted as part of the facility planning process for a CAH in rural North Carolina. Hospital staff participated in a survey exploring their satisfaction with the overall physical environment privacy, space allocation, and department adjacency. An open-ended question asked staff to elaborate on needed improvements and changes in their department., Results: Findings show low satisfaction levels for space allocations for emergency department, lab, surgery, and wound care. Safety and quality were the two emerging outcomes of the physical environment's shortcomings. Two clusters emerged from the content analysis, representing facility needs (rightly sized spaces, functional needs, COVID-19 needs, and improved access) and ambient conditions (clutter, visibility, flooring quality, noise, privacy, cleanliness, aesthetics, and temperature)., Conclusion: The findings from this study suggest that the interior and exterior facility and ambient conditions of the CAH play a key role in quality and safety outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Sex differences in stroke exist, including variation in stroke risk and outcome. Differences in thrombin generation may contribute to this variation between females and males. To examine this, we assessed sex differences in thrombin generation between females and males with acute ischemic stroke and the relationship to blood cell gene expression. In 97 patients with acute ischemic stroke, thrombin generation was measured by thrombin generation assay. Blood cell gene expression was measured by microarray. Differences in thrombin generation between sexes were identified and the relationship to blood cell gene expression examined. Genes associated with sex differences in thrombin generation were analyzed by functional pathway analysis. Females and males had similar overall capacity to generate thrombin. The peak thrombin generated in females was 468.8 nM (SD 91.6), comparable to males (479.3nM;SD 90.8; p = 0.58). Lag time, time to peak thrombin, and endogenous thrombin potential were also similar between females and males. While overall thrombin generation was comparable between females and males with stroke, differences in genes that promote this thrombin generation exist. Females with high peak thrombin had an increase in genes that promote thrombosis, and platelet activation. In contrast, males with high peak thrombin had a decrease in genes involved in thrombus degradation. Females and males with acute ischemic stroke have similar capacity to generate thrombin, however, differences may exist in how this thrombin generation is achieved, with females having increased thrombin signaling, and platelet activation, and males having decreased thrombus degradation. This suggests regulatory differences in thrombosis may exist between females and males that may contribute to sex differences in stroke., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: The goal was to evaluate the effect of resveratrol (RS) and combination therapy of RS and donepezil (DPZ), on the numerical expression of microglial cells and astrocytes, in the frontal cortex, regions of the hippocampus in colchicine-induced Alzheimer's disease (AD) model., Methods: The study involved male albino Wistar rats of three months, age and consisted of 6 groups, with six animals each. The immunohistochemical staining with mouse monoclonal anti-human CD 68 and mouse monoclonal anti-GFAP was performed to assess the number of microglial cells and astrocytes, respectively., Results: AD group showed an increase in the number of microglia, and the numbers declined in the treatment groups, RS 10, RS 20, RS10/10 and DPZ + RS ( p  < 0.001). Astrocyte count was increased in the treatment groups in contrast to the AD group ( p  < 0.05). The DPZ + RS combination group revealed substantial elevation in the number of astrocytes and decreased microglial number among all the groups ( p  < 0.001)., Conclusion: RS administration has diminished the microglial number and elevated the number of astrocytes. The elevated reactive astrocytes have decreased the microglial population. However, the limitation of our study is utilizing the colchicine for the induction of neurodegeneration. Using the transgenic models of AD may give a better insight into the pathogenesis and effect of RS. Another limitation of this study is the administration of RS and DPZ through different routes. The prospects of this research include studying the probiotic nature of RS and the effect of RS in other neurodegenerative disorders., Competing Interests: Conflict of interestThe authors of this manuscript declare that there are no conflicts of interest associated with this manuscript., (© The Author(s) 2023.)

Background and Aim: Social isolation stress (SIS) and individual housing have been shown to cause abnormal cognitive insufficiencies, altered anxiety levels, and signs of psychiatric diseases. Acorus calamus (AC), commonly known as Sweet Flag, has been widely used in India to treat neurological, metabolic, and respiratory disorders, indicating its potential therapeutic value. This study aimed to determine the antidepressant and antioxidative effects of AC on rats subjected to long-term, social isolation-induced stress., Materials and Methods: This study involved 2-month-old male rats (24) weighing approximately 180-200 g bred in-house. The rats were divided into four groups (n = 6): Group 1 received saline, Group 2 received SIS, Group 3 received only 50 mg/kg AC, and Group 4 received 50 mg/kg AC and SIS for 6 weeks. After this, behavioral, biochemical, and neuronal assays were conducted., Results: Behavioral experiments showed significantly higher activity levels (p < 0.001) in AC-treated rats than in the SIS group. In addition, rats subjected to SIS with AC treatment exhibited enhanced total antioxidants, superoxide dismutase, and neuronal assays compared to rats subjected to SIS alone., Conclusion: Acorus calamu s treatment improved the antidepressant and antioxidant potential against SIS in rat brain tissue. Moreover, we proved that AC can effectively reverse the neurotoxicity induced by SIS in animal models. As we battle against the coronavirus disease 2019 pandemic and social isolation, AC could be considered a supplementary treatment to alleviate depressive-like symptoms in our present-day lifestyle., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Rai, et al.)

Background: Throughout the COVID-19 pandemic, many areas of medicine transitioned to virtual care. For patients with diabetes admitted to hospital, this included diabetes education and insulin teaching. Shifting to a virtual model of insulin teaching created new challenges for inpatient certified diabetes educators (CDE)., Objective: We advanced a quality improvement project to improve the efficiency of safe and effective virtual insulin teaching throughout the COVID-19 pandemic. Our primary aim was to reduce the mean time between CDE referral to successful inpatient insulin teach by 0.5 days., Design, Setting, Participants: We conducted this initiative at two large academic hospitals between April 2020 and September 2021. We included all admitted patients with diabetes who were referred to our CDE for inpatient insulin teaching and education., Intervention: Alongside a multidisciplinary team of project stakeholders, we created and studied a CDE-led, virtual (video conference or telephone) insulin teaching programme. As tests of change, we added a streamlined method to deliver insulin pens to the ward for patient teaching, created a new electronic order set and included patient-care facilitators in the scheduling process., Main Outcome and Measures: Our main outcome measure was the mean time between CDE referral and successful insulin teach-back. Our process measure was the percentage of successful insulin pen deliveries to the ward for teaching. As balance measures, we captured the percentage of patients with a successful insulin teach, the time between insulin teach and hospital discharge, and readmissions to hospital for diabetes-related complications., Results: Our tests of change improved the efficiency of safe and effective virtual insulin teaching by 0.27 days. The virtual model appeared less efficient than usual in-person care., Conclusions: In our centre, virtual insulin teaching supported patients admitted to hospital through the pandemic. Improving the administrative efficiency of virtual models and leveraging key stakeholders remain important for long-term sustainability., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We report the numerical and experimental study of probe pulse deformation in a forward-pumped distributed Raman amplifier on a 40-km standard single mode fiber. Distributed Raman amplification can improve the range of OTDR-based sensing systems, but it could result in pulse deformation. A smaller Raman gain coefficient can be used to mitigate pulse deformation. The sensing performance can still be maintained by compensating for the decrease in the Raman gain coefficient by increasing the pump power. The tunability of the Raman gain coefficient and pump power levels are predicted while keeping the probe power below the modulation instability limit.

Diabetes mellitus is a fast-growing chronic metabolic condition caused by insulin deficiency or resistance, leading to lifelong insulin use. It has become one of the world's most difficult non-communicable diseases. The goal of this study was to view the effectiveness of the combined method of macro- and microencapsulation for islet transplantation. The process of 3D printing is used to make macroencapsulation bags with regulated diffusion properties thanks to the emerging small pored channels. The ink used to manufacture 3D-printed bags with controlled specifications was polyurethane solution (13% w/v). Swelling experiments revealed that there was very little swelling and that the membrane maintained its structural stability. Alginate beads (made from 5% w/v solution) were used to microencapsulate islet cell clusters. Direct contact assay was used to confirm in vitro cytocompatibility. The insulin release from the encapsulated rabbit islets was confirmed using a glucose challenge assay. When challenged with 20 mM glucose on day 7, the encapsulated islet cells released insulin at a rate of 9.72 ± 0.65 mU/L, which was identical to the RIN-5F islet cell line control, confirming the functioning of the encapsulated islets. After 21 days of culture, the islets were shown to be viable utilizing a live-dead assay. As a result, our work demonstrates that 3D printing for macroencapsulating cells, as well as microencapsulation with alginates, is a viable scale-up technology with great potential in the field of pancreatic islet transplantation., (© 2022. The Author(s), under exclusive licence to Islamic Azad University.)

microRNA (miRNA) are important regulators of gene expression. miRNA have the potential as a treatment to modulate genes, pathways and cells involved in ischemic stroke. In this review, we specifically present miRNA in stroke as a treatment to decrease thrombosis, reduce blood brain barrier (BBB) disruption and hemorrhagic transformation (HT), modulate inflammation, and modify angiogenesis. miRNA as a treatment for stroke is an emerging area with evidence from animal studies demonstrating its potential. While no miRNA is currently approved for human use, several have shown promise in clinical trials to treat medical conditions, such as miR-122 for hepatitis C. The role of miRNA as a treatment for specific applications in ischemic stroke is presented including a discussion of the benefits and barriers of miRNA as a treatment, and directions for future advancement., Competing Interests: Declaration of competing interest Authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Rationale: Mycetoma is a chronic granulomatous infection that involves the skin and subcutaneous tissue which presents as an abscess with multiple draining sinuses. It is common in the tropical and subtropical regions where the conditions favour the growth of the soil saprophytes - fungi and bacteria., Patient Concerns: We report the rare case of a 62-year-old patient who presented with a soft-tissue overgrowth in the mandibular posterior ridge area for eight months., Diagnosis: The patient was diagnosed with eumycetoma, with foreign-body reaction based on clinical and histopathological examination which revealed characteristic brown-coloured amorphous grains., Treatment: The lesion was surgically excised under local anaesthesia., Outcomes: On the seventh day post-operative follow-up, the patient was relieved of pre-operative symptoms and the surgical site had healed well., Take-Away Lessons: This particular case of eumycetoma had an unusual site and appearance, making the clinical diagnosis confusing with other reactionary lesions of the oral cavity., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Annals of Maxillofacial Surgery.)

We describe a case of cardiac arrest with pulmonary embolism and deep venous thrombosis diagnosed by point-of-care ultrasound, which resulted in a favorable outcome. In this article, we have also delineated bradycardia as an atypical sign of pulmonary embolism and explained the potential mechanism behind it., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Cheema et al.)

Pantothenate (Pan) is an essential nutrient required by both the mosquito vector and malaria parasite. We previously demonstrated that increasing pantothenate kinase (PanK) activity and co-enzyme A (CoA) biosynthesis led to significantly decreased parasite infection prevalence and intensity in the malaria mosquito Anopheles stephensi. In this study, we demonstrate that Pan stores in A. stephensi are a limited resource and that manipulation of PanK levels or activity, via small molecule modulators of PanK or transgenic mosquitoes, leads to the conversion of Pan to CoA and an overall reduction in Pan levels with minimal to no effects on mosquito fitness. Transgenic A. stephensi lines with repressed insulin signaling due to PTEN overexpression or repressed c-Jun N-terminal kinase (JNK) signaling due to MAPK phosphatase 4 (MKP4) overexpression exhibited enhanced PanK levels and significant reductions in Pan relative to non-transgenic controls, with the PTEN line also exhibiting significantly increased CoA levels. Provisioning of the PTEN line with the small molecule PanK modulator PZ-2891 increased CoA levels while provisioning Compound 7 decreased CoA levels, affirming chemical manipulation of mosquito PanK. We assessed effects of these small molecules on A. stephensi lifespan, reproduction and metabolism under optimized laboratory conditions. PZ-2891 and Compound 7 had no impact on A. stephensi survival when delivered via bloodmeal throughout mosquito lifespan. Further, PZ-2891 provisioning had no impact on egg production over the first two reproductive cycles. Finally, PanK manipulation with small molecules was associated with minimal impacts on nutritional stores in A. stephensi mosquitoes under optimized rearing conditions. Together with our previous data demonstrating that PanK activation was associated with significantly increased A. stephensi resistance to Plasmodium falciparum infection, the studies herein demonstrate a lack of fitness costs of mosquito Pan depletion as a basis for a feasible, novel strategy to control parasite infection of anopheline mosquitoes., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Objectives: Thrombosis is central to the pathogenesis of acute ischemic stroke, with higher thrombin generation being associated with increased stroke risk. The immune system may contribute to thrombin generation in stroke and thus may offer novel strategies for stroke prevention. This study addresses the research question regarding the relationship of thrombin generation to leukocyte gene expression in patients with acute ischemic stroke., Methods: We isolated RNA from whole blood and examined the relationship to thrombin generation capacity in patients with acute ischemic stroke. Due to its effects on thrombin generation, patients on anticoagulants were excluded from the study. The relationship of gene expression with peak thrombin was evaluated by analysis of covariance across peak thrombin quartiles adjusted for sex and age., Results: In 97 patients with acute ischemic stroke, peak thrombin was variable, ranging from 252.0 to 752.4 nM. Increased peak thrombin was associated with differences in thromboinflammatory leukocyte gene expression, including a decrease in ADAM metallopeptidase with thrombospondin type 1 motif 13 and an increase in nuclear factor κB (NF-κB)-activating protein, protein disulfide isomerase family A member 5, and tissue factor pathway inhibitor 2. Pathways associated with peak thrombin included interleukin 6 signaling, thrombin signaling, and NF-κB signaling. A linear discriminant analysis model summarizing the immune activation associated with peak thrombin in a first cohort of stroke could distinguish patients with low peak thrombin from high peak thrombin in a second cohort of 112 patients with acute ischemic stroke., Discussion: The identified genes and pathways support a role of the immune system contributing to thrombus formation in patients with stroke. These may have relevance to antithrombotic strategies for stroke prevention., (© 2022 American Academy of Neurology.)

Background: Infection prevention and control (IPC) activities play a large role in preventing the transmission of SARS-CoV-2 in healthcare settings. This study describes the state of IPC preparedness within health facilities in Nigeria during the early phase of coronavirus disease (COVID-19) pandemic., Methods: We carried out a cross sectional study of health facilities across Nigeria using a COVID-19 IPC checklist adapted from the U.S Centers for Disease Control and Prevention. The IPC aspects assessed were the existence of IPC committee and teams with terms of reference and workplans, IPC training, availability of personal protective equipment and having systems in place for screening, isolation and notification of COVID-19 patients. Existence of the assessed aspects was regarded as preparedness in that aspect., Results: In total, 461 health facilities comprising, 350 (75.9%) private and 111 (24.1%) public health facilities participated. Only 19 (4.1%) health facilities were COVID-19 treatment centres with 68% of these being public health facilities. Public health facilities were better prepared in the areas of IPC programme with 69.7% of them having an IPC focal point versus 32.3% of private facilities. More public facilities (59.6%) had an IPC workplan versus 26.8% of private facilities. Neither the public nor the private facilities were adequately prepared for triaging, screening, and notifying suspected cases, as well as having trained staff and equipment to implement triaging., Conclusions: The results highlight the need for government, organisations and policymakers to establish conducive IPC structures to reduce the risk of COVID-19 transmission in healthcare settings., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Given that older Aedes aegypti (L.) mosquitoes typically pose the greatest risk of pathogen transmission, the capacity to age grade wild Ae. aegypti mosquito populations would be a valuable tool in monitoring the potential risk of arboviral transmission. Here, we compared the effectiveness of near-infrared spectroscopy (NIRS) to age grade field-collected Ae. aegypti with two alternative techniques-parity analysis and transcript abundance of the age-associated gene SCP1 . Using lab-reared mosquitoes of known ages from three distinct populations maintained as adults under laboratory or semi-field conditions, we developed and validated four NIRS models for predicting the age of field-collected Ae. aegypti . To assess the accuracy of these models, female Ae. aegypti mosquitoes were collected from Maricopa County, AZ, during the 2017 and 2018 monsoon season, and a subset were age graded using the three different age-grading techniques. For both years, each of the four NIRS models consistently graded parous mosquitoes as significantly older than nulliparous mosquitoes. Furthermore, a significant positive linear association occurred between SCP1 and NIRS age predictions in seven of the eight year/model combinations, although considerable variation in the predicted age of individual mosquitoes was observed. Our results suggest that although the NIRS models were not adequate in determining the age of individual field-collected mosquitoes, they have the potential to quickly and cost effectively track changes in the age structure of Ae. aegypti populations across locations and over time.

Hippocampus is the significant component of the limbic lobe, which is further subdivided into the dentate gyrus and parts of Cornu Ammonis. It is the crucial region for learning and memory; its sub-regions aid in the generation of episodic memory. However, the hippocampus is one of the brain areas affected by Alzheimer's (AD). In the early stages of AD, the hippocampus shows rapid loss of its tissue, which is associated with the functional disconnection with other parts of the brain. In the progression of AD, atrophy of medial temporal and hippocampal regions are the structural markers in magnetic resonance imaging (MRI). Lack of sirtuin (SIRT) expression in the hippocampal neurons will impair cognitive function, including recent memory and spatial learning. Proliferation, differentiation, and migrations are the steps involved in adult neurogenesis. The microglia in the hippocampal region are more immunologically active than the other regions of the brain. Intrinsic factors like hormones, glia, and vascular nourishment are instrumental in the neural stem cell (NSC) functions by maintaining the brain's microenvironment. Along with the intrinsic factors, many extrinsic factors like dietary intake and physical activity may also influence the NSCs. Hence, pro-neurogenic lifestyle could delay neurodegeneration., Competing Interests: Conflict of interestThe authors of this manuscript declare that there are no conflicts of interest associated with this manuscript., (© The Author(s) 2022.)

Zebrafish have gained momentum as a leading experimental model in recent years. At present, the zebrafish vertebrate model is increasingly used due to its multifactorial similarities to humans that include genetic, organ, and cellular factors. With the emergence of novel research techniques that are very expensive, it is necessary to develop affordable and valid experimental models. This review aimed to highlight some of the most important similarities between zebrafish and humans by emphasizing the relevance of the first in simulating neurological disorders and craniofacial deformity., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Rai, et al.)

Embolic stroke of unknown source (ESUS) represents one in five ischemic strokes. Ipsilateral non-stenotic carotid plaques are identified in 40% of all ESUS. In this narrative review, we summarize the evidence supporting the potential causal relationship between ESUS and non-stenotic carotid plaques; discuss the remaining challenges in establishing the causal link between non-stenotic plaques and ESUS and describe biomarkers of potential interest for future research. In support of the causal relationship between ESUS and non-stenotic carotid plaques, studies have shown that plaques with high-risk features are five times more prevalent in the ipsilateral vs. the contralateral carotid and there is a lower incidence of atrial fibrillation during follow-up in patients with ipsilateral non-stenotic carotid plaques. However, non-stenotic carotid plaques with or without high-risk features often coexist with other potential etiologies of stroke, notably atrial fibrillation (8.5%), intracranial atherosclerosis (8.4%), patent foramen ovale (5-9%), and atrial cardiopathy (2.4%). Such puzzling clinical associations make it challenging to confirm the causal link between non-stenotic plaques and ESUS. There are several ongoing studies exploring whether select protein and RNA biomarkers of plaque progression or vulnerability could facilitate the reclassification of some ESUS as large vessel strokes or help to optimize secondary prevention strategies., 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 © 2021 Kamtchum-Tatuene, Nomani, Falcione, Munsterman, Sykes, Joy, Spronk, Vargas and Jickling.)

Alternative roles for sweat production beyond thermoregulation, considered less frequently, include chemical signaling. We identified the presence of a well-established rodent urinary pheromone, major urinary protein (MUP) in sweat ductules of the footpad dermal skin of mice. A hindpaw sweat proteomic analysis in hindpaw sweat samples collected in rats and generated by unmyelinated axon activation, identified seven lipocalin family members including MUP and 19 additional unique proteins. Behavioural responses to sniffing male mouse foot protein lysates suggested avoidance in a subset of male mice, but were not definitive. Rodent hindpaw sweat glands secrete a repertoire of proteins that include MUPs known to have roles in olfactory communication., (© 2021 Anatomical Society.)

The aim of this study was to determine the malondialdehyde (MDA) level and superoxide dismutase ( SOD) activity in colchicine induced Alzheimer's disease ( AD), resveratrol ( RS) treated and RS + donepezil (DPZ) treated rat models. The objective was to compare the MDA level and SOD activity among these rat models. The present study included 3 months old male albino Wistar rats, which were in-house bred and weighting about 220-250 g. The rats were divided into nine subgroups which included control, sham, AD induced, RS treated and DPZ treated groups in different doses and combinations. The lipid peroxidation product for MDA in the brain homogenate was measured by estimating the levels of thiobarbituric acid reactive substance. Estimation of SOD was done by the method of autoxidation of pyrogallol by Marklund and Marklund. There was a marked increase in the MDA levels in AD induced group in comparison to the control group ( p  < 0.05). The SOD activity was higher in the RS 10 and RS 20 treated groups in contrast to the AD group ( p  < 0.05). In DPZ + RS group, there was a substantial increase in the SOD activity ( p  < 0.05). It is also observed that the RS 20 treatment group showed higher SOD activity than the RS 10 group ( p  < 0.05). This study showed that, AD induced group had elevated levels of MDA, which indicates the poor oxidative stress-defence mechanism. The RS 10 and RS 20 groups showed higher SOD activity in comparison to the AD group, which indicated the improved oxidative stress-defence mechanism. The RS + DPZ group showed higher SOD activity, indicating a synergistic effect of DPZ and RS., Competing Interests: Conflict of interestAll the authors of this study stated that there are no conflicts of interest, which are associated with this manuscript., (© The Author(s) 2021.)

Hemorrhagic transformation (HT) is a common complication in patients with acute ischemic stroke. It occurs when peripheral blood extravasates across a disrupted blood brain barrier (BBB) into the brain following ischemic stroke. Preventing HT is important as it worsens stroke outcome and increases mortality. Factors associated with increased risk of HT include stroke severity, reperfusion therapy (thrombolysis and thrombectomy), hypertension, hyperglycemia, and age. Inflammation and the immune system are important contributors to BBB disruption and HT and are associated with many of the risk factors for HT. In this review, we present the relationship of inflammation and immune activation to HT in the context of reperfusion therapy, hypertension, hyperglycemia, and age. Differences in inflammatory pathways relating to HT are discussed. The role of inflammation to stratify the risk of HT and therapies targeting the immune system to reduce the risk of HT are presented., 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 © 2021 Spronk, Sykes, Falcione, Munsterman, Joy, Kamtchum-Tatuene and Jickling.)

The COVID-19 pandemic has presented significant challenges to services providing emergency care, in both the community and hospital setting. The Physician Response Unit (PRU) is a Community Emergency Medicine model, working closely with community, hospital and pre-hospital services. In response to the pandemic, the PRU has been able to rapidly introduce novel pathways designed to support local emergency departments (EDs) and local emergency patients. The pathways are (1) supporting discharge from acute medical and older people's services wards into the community; (2) supporting acute oncology services; (3) supporting EDs; (4) supporting palliative care services. Establishing these pathways have facilitated a number of vulnerable patients to access patient-focussed and holistic definitive emergency care. The pathways have also allowed EDs to safely discharge patients to the community, and also mitigate some of the problems associated with trying to maintain isolation for vulnerable patients within the ED. Community Emergency Medicine models are able to reduce ED attendances and hospital admissions, and hence risk of crowding, as well as reducing nosocomial risks for patients who can have high-quality emergency care brought to them. This model may also provide various alternative solutions in the delivery of safe emergency care in the postpandemic healthcare landscape., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This descriptive case study of ambulatory care center typologies builds a layout-based approach to patient-centered care and care team work using theory and methods from space syntax and a recently developed approach to floorplan analysis focused on visibility., Background: Calibrating support for care team work and patient centeredness is a persistent dilemma in ambulatory care settings., Method: A review of literature and floorplan layout analysis are used., Results: The center-stage layout more strongly integrates staff and patients, while the onstage-offstage layout provides greater privacy to the care team. The integration values for exam rooms in each layout were roughly equivalent. Analysis of variations on each floor plan demonstrates ways relatively small variations can modulate visibility conditions without altering integration patterns., Conclusion: Decoupling design of immediate visual properties and relational layout properties can act as a strategy to address competing demands.

Background and Objectives: International and national health policies advocate greater integration of emergency and community care. The Physician Response Unit (PRU) responds to 999 calls 'taking the Emergency Department to the patient'. Operational since 2001, the service was reconfigured in September 2017. This article presents service activity data and implications for the local health economy from the first year since remodelling., Methods: A retrospective descriptive analysis of a prospectively maintained database was undertaken. Data collected included dispatch information, diagnostics and treatments undertaken, diagnosis and disposition. Treating clinical teams recorded judgments whether patients managed in the community would have been (1) conveyed to an emergency department (ED)and (2) admitted to hospital, in the absence of the PRU. Hospital Episode Statistics data and NHS referencing costs were used to estimate the monetary value of PRU activity., Results: 1924 patients were attended, averaging 5.3 per day. 1289 (67.0%) patients were managed in the community. Based on the opinion of the treating team, 945 (73.3%) would otherwise have been conveyed to hospital, and 126 (9.7%) would subsequently have been admitted. The service was estimated to deliver a reduction of 868 inpatient bed days and generate a net economic benefit of £530 107., Conclusions: The PRU model provides community emergency medical care and early patient contact with a senior clinical decision-maker. It engages with community providers in order to manage 67.0% of patients in the community. We believe the PRU offers an effective model of community emergency medicine and helps to integrate local emergency and community providers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability., Methods: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT., Results: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT., Discussion: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.

Introduction: The landscape for the treatment of metastatic melanoma has been revolutionized with the introduction immune checkpoint inhibitors. Immune checkpoint inhibitors have now become the standard of care for the treatment of cancers. These immune agents including programmed death receptor-1 inhibitors, programmed death-ligand 1 inhibitors and cytotoxic T-lymphocyte antigen-4 inhibitors have shown promising results but have been associated with numerous immune-related complications. Pembrolizumab, a programmed death receptor-1 inhibitor, has been associated with a number of immune-related adverse events affecting multiple organ systems including integument, ocular, endocrine, cardiovascular, pulmonary, renal, gastrointestinal, and musculoskeletal system., Case Report: We present a case of an 88-year-old Caucasian male with metastatic melanoma of the face with metastasis to the right fifth cranial nerve and into the right cavernous sinus. He underwent resection of the melanoma and was placed on pembrolizumab at 2 mg/kg every three weeks. Interestingly, 24 months on pembrolizumab therapy, he developed corneal erosions, oral and genital ulcerations., Management and Outcome: Patient completed his 24 months of pembrolizumab and was started on prednisone and colchicine with improvement in his symptoms. At his follow-up eight months, he had recurrence of an oral ulcer., Discussion: Here we present a rare case of an elderly male on pembrolizumab who suffered from corneal erosions, oral and genital ulcers, a syndrome similar to Behcet's disease. Given that pembrolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the wide range immune-related adverse events including the possible Behcet's-like syndrome presentation.

Some individuals recover from the pain of nerve trauma within 12 months or less whereas others experience life-long intractable pain. This transition between reversible pain and the establishment of chronic neuropathic pain is poorly understood. We examined the role of persistent inflammation in the dorsal root ganglia (DRG) in the long-term maintenance of mechanical allodynia; an index of neuropathic pain. Male Sprague-Dawley rats underwent chronic constriction injury (CCI), spared nerve injury (SNI) or sham surgery. Both CCI and SNI animals displayed robust mechanical allodynia in the ipsilateral paw at 7 d post-surgery; however, only SNI animals maintained mechanical allodynia at 42 d post-surgery. DRGs were extracted at 7 d or 42 d post-surgery to assess inflammation via rt-qPCR or immunohistochemistry to measure colony stimulating factor 1 (CSF1) expression, satellite glial cell (SGC) activation, presence of Iba1 positive macrophages and interleukin1 β (IL-1β) mRNA levels. Whereas DRGs from SNI animals continued to display inflammatory markers at 42 d, those from CCI animals did not. Moreover, the level of allodynia displayed by each individual animal correlated with the extent of DRG inflammation. These data support the hypothesis that the amount of CSF1 immunoreactivity and the persistence of inflammation in ipsilateral DRGs contribute to the difference between transient and persistent mechanical allodynia observed in the CCI and SNI models. We also suggest that feedback loops involving cytokines and neurotransmitters may contribute to increased DRG activity in chronic neuropathic pain. Consequently, targeting persistent CSF1 production and peripheral neuroinflammation may be an effective approach to the management of chronic neuropathic pain., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is a neurodegenerative disorder, which is commonly seen in older individuals. This is characterized by cognitive dysfunction, which leads to dementia. Pharmacological treatments for AD are mainly targeted on its symptoms like memory loss and cognitive impairment. The pathophysiology involved in AD is intra-neuronal accumulation of hyper-phosphorylated tau protein as neurofibrillary tangle and extra cellular beta amyloid plaque deposition, which is due to oxidative stress. Here we review the neuro-protective effects of Resveratrol (RSV) and its treatment efficacy in AD. RSV is a naturally available polyphenolic compound, which has antioxidant, anti-cancerous, anti-inflammatory and anti-aging properties. RSV crosses blood brain barrier and exerts its antioxidant effect by enhancing the anti-oxidant enzymes. RSV is involved in Sirtuin (SIRT1) mediated lifespan extension activity. RSV has reduced glial activation and helped in increasing the hippocampal neurogenesis. RSV was able to decrease the expression of amyloid precursor protein, along with improvement of spatial working memory. Since RSV acts as an antioxidant, it can be safely used as oral drug.

Cysts of the oral cavity are among the most commonly encountered biopsy specimen in histopathology. Shear categorized the cysts associated with maxillary antrum under four subheadings - mucocoele, retention cyst, pseudocyst, and postoperative maxillary cyst (PMC). PMC is also known as surgical ciliated cyst, postoperative paranasal cyst, or respiratory implantation cyst. Although it constitutes 20% of oral cysts in Japan, it is quite rare in the other parts of the world. Herewith, we report a case of a 65-year-old female who presented with the complaint of palatal swelling and having a history of maxillary sinus surgery 30 years ago., Competing Interests: None

The artificial joints, for example, knee and hip implants, are widely used for the treatment of degenerative joint diseases and trauma. The current most common material choice for clinically used implants is the combination of polymer-on-metal structures. Unfortunately, these joints often suffer from high friction and wear, leading to associated inflammation and infection and ultimate failure of the artificial joints. Here, we propose an alternative solution to this tribologically induced failure of the joint materials. We demonstrate that the friction and wear behavior of ultrahigh-molecular-weight polyethylene (UHMWPE) and titanium tribopair, used to mimic the artificial joint interface, can be improved by introducing nanodiamond (ND) particles in the sliding contact. Characterization of the wear track using energy-dispersive spectroscopy and Raman spectroscopy revealed that the tribofilm formed from embedded NDs during sliding significantly suppressed the wear of the UHMWPE surface. In addition to the improved lubrication characteristics, NDs exhibit high biocompatibility with the bone cells and promising antibacterial properties against Staphylococcus aureus , the most common strain associated with artificial joint infection. These results indicate that NDs can be used as a promising nontoxic human-body lubricant with antiwear and antibacterial features, thus demonstrating their great potential to treat artificial joint complications through intra-articular injection.

Fetal growth restriction (FGR) is associated with threefold to fourfold increased risk of stillbirth. Identifying FGR, through its commonly used surrogate-the small-for-gestational-age (SGA, estimated fetal weight and/or abdominal circumference <10th centile) fetus-and instituting fetal surveillance and timely delivery decrease stillbirth risk. Methods available to clinicians for antenatal identification of SGA fetuses have surprisingly poor sensitivity. About 80% of cases remain undetected. Measuring the symphysis-fundal height detects only 20% of SGA fetuses, and even universal third trimester ultrasound detects, at best, 57% of those born SGA. There is an urgent need to find better ways to identify this at-risk cohort. This review summarises efforts to identify molecular biomarkers (proteins, metabolites, or ribonucleic acids) that could be used to better predict FGR. Most studies examining potential biomarkers to date have utilised case-control study designs without proceeding to validation in independent cohorts. To develop a robust test for FGR, large prospective studies are required with a priori validation plans and cohorts. Given that current clinical care detects 20% of SGA fetuses, even a screening test with ≥60% sensitivity at 90% specificity could be clinically useful, if developed. This may be an achievable aspiration. If discovered, such a test may decrease stillbirth., (© 2019 John Wiley & Sons, Ltd.)

Among the many factors responsible for the cognitive decline in Alzheimer's disease, beta amyloid protein and plaque formation is crucial. This amyloid pathology is associated with activation of glial cells and oxidative stress but whether oxidative stress activates beta amyloid protein in the neurons is not clear. Further the expression of microglia is also known to vary during pathogenesis of beta amyloid plaques. The aim of the present study is to evaluate the antioxidant effect of NAC on amyloid pathology and cognition and also to investigate the link between amyloid pathology and glial cells activation. Intracerebroventricular colchicine in rats known mimics human AD in many aspects including memory loss, oxidative stress, and hyper phosphorylation of tau protein. The animal groups consisted of age matched control, sham operated, AD, and NAC treated in AD models of rats. Cognitive function was evaluated in active avoidance test; beta amyloid protein, beta amyloid plaques, astrocytes, and microglia cells were quantified using immunohistochemistry in hippocampal and prefrontal cortices. Colchicine has resulted in significant cognitive loss, increased intraneuronal beta amyloid protein expression, increased reactive astrocytes, and activated microglia in all the regions of the hippocampus and prefrontal cortices. The antioxidant NAC has reversed the cognitive deficits and inhibited microglia activation but failed to inhibit BAP expression and astrocytosis. Intraneuronal BAP accumulation is deleterious and known to adversely affect cognition, but in this study in spite of intraneuronal BAP accumulation, the cognition is restored. It can be postulated that NAC might have reversed the effect of intraneuronal beta amyloid protein by acting on some downstream compensatory mechanisms which needs to be explored.

Members of the College of Physicians and Surgeons of Ontario Endocrinology and Metabolism Peer Review Network have been involved in a quality improvement project to help standardize the peer assessment of physicians practicing in endocrinology and metabolism. This has included developing state-of-the-art summaries of common endocrine problems by Canadian experts in endocrinology and metabolism. These tools have been developed in response to the educational needs, as identified by peer reviewers, of practicing endocrinologists in Ontario. These pedagogical tools aim not only to standardize the documentation of the clinical performance of endocrinologists but also to make the process more transparent and to improve the quality of patient care in Ontario. This article summarizes the project and also provides the tools developed for the endocrinology and metabolism section of the College of Physicians and Surgeons of Ontario., (Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Spindle cell neoplasms comprise a diverse collection of benign and malignant tumors. These tumors are uncommon in the oral cavity, accounting for <1% of all tumors of oral region. Sarcomatoid squamous cell carcinoma (SSCC), also known as spindle cell carcinoma or Lane's tumor, is a rare and peculiar biphasic malignant neoplasm that occurs mainly in the upper aerodigestive tract. It is a variant of squamous cell carcinoma which has spindled or pleomorphic tumor cells which simulate a true sarcoma, but are epithelial in origin. It is an unusual aggressive variant that frequently recurs and metastasizes, reinforcing the importance of its correct diagnosis. We report two cases of SSCC with immunohistochemical findings., Competing Interests: There are no conflicts of interest.

Alzheimer's disease (AD) is characterized by the accumulation of neurofibrillary tangles (NFT), deposition of beta amyloid plaques, and consequent neuronal loss in the brain tissue. Oxidative stress to the neurons is often attributed to AD, but its link to NFT and β-amyloid protein (BAP) still remains unclear. In an animal model of AD, we boosted the oxidative defense by N -Acetyl cysteine (NAC), a precursor of glutathione, a powerful antioxidant and free radical scavenger, to understand the link between oxidative stress and NFT. In mimicking AD, intracerebroventricular (ICV) colchicine, a microtubule disrupting agent also known to cause oxidative stress was administered to the rats. The animal groups consisted of an age-matched control, sham operated, AD, and NAC treated in AD models of rats. Cognitive function was evaluated in a passive avoidance test; neuronal degeneration was quantified using Nissl staining. NFT in the form of abnormal tau expression in different regions of the brain were evaluated through immunohistochemistry using rabbit anti-tau antibody. ICV has resulted in significant cognitive and neuronal loss in medial prefrontal cortex (MFC) and all the regions of the hippocampus. It has also resulted in increased accumulation of intraneuronal tau in the hippocampus and MFC. NAC treatment in AD model rats has reversed the cognitive loss and neuronal degeneration. The intraneuronal tau expression also minimized with NAC treatment in AD model rats. Thus, our findings suggest that an antioxidant supplement during the progression of AD is likely to prevent neuronal degeneration by minimizing the neurofibrillary degeneration in the form of tau accumulation.

Type 2 diabetes (T2D) has reached pandemic proportions worldwide. Almost half of T2D patients suffer from polyneuropathy that can present as paresthesia, hyperalgesia, allodynia, or hypoesthesia. Therapeutic treatment options are largely incomplete, suggesting new avenues of research are needed. Herein, we introduce the African Nile Grass rat (NGR), which develops T2D solely by diet manipulation, as a novel T2D polyneuropathy model. The purpose of this study was to first characterize T2D-induced polyneuropathy in the NGRs before highlighting their strength as a potential prediabetic model of T2D. NGRs with long-term T2D exhibit hallmark features of polyneuropathy such as decreased motor nerve conduction velocity, intraepidermal denervation, and hyposensitivity to noxious mechanical and thermal stimulation. At the dorsal root ganglia, T2D neurons have altered sodium channel expression, specifically increased Nav1.7 and Nav1.9, and their surrounding satellite glial cells express glial fibrillary acidic protein. Now that these T2D NGRs have been characterized and shown to have a similar presentation to human and other animal models of T2D, the strength of this diet-induced model can be exploited. The prediabetic changes can be observed over their long progression to develop T2D which may allow for a therapeutic window to prevent T2D before permanent damage occurs.

Rhabdomyosarcoma is a malignant neoplasm of mesenchymal cells, showing varying degrees of striated muscle cell differentiation. It predominantly occurs in children while rarely found in adults and involvement of the oral cavity accounts for only 10%-12% of all head-and-neck cases. Herewith, we present a rare case of spindle cell rhabdomyosarcoma in a 52-year old male, involving the mandibular gingiva, and describe the clinical, radiological, histopathological and immunohistochemical findings., Competing Interests: There are no conflicts of interest.

Background: Mucins are high-molecular-weight glycoproteins with a high O-linked carbohydrate content, which are synthesized by many secretory epithelial cells as membrane-bound and/or secreted products. Mucin-1 (MUC1) is a transmembrane mucin that protects and lubricates the mucous membranes of the human body and involves itself in various cellular functions such as growth, differentiation and signaling. An aberrant expression of MUC1 has been demonstrated in various human cancers. Many studies on MUC1 expression have been conducted on a variety of neoplastic lesions other than head-and-neck region. In this study, an attempt has been made to evaluate the MUC1 immunoexpression in oral squamous cell carcinoma (OSCC) and normal oral mucosa (NOM)., Aims: This study aims to compare and correlate the immunoexpression of MUC1 in NOM and OSCC using immunohistochemical technique., Settings and Design: Thirty patients of OSCC formed the study group and thirty patients were included in the control group (NOM). Formalin-fixed paraffin wax blocks were prepared from the tissue samples obtained., Materials and Methods: Immunohistochemistry (IHC) for MUC1 was performed, and the overall percentage of positive cells along with distribution and localization of immunoexpression was studied., Statistical Analysis: Pearson's Chi-square test was used. P <0.05 was considered to be statistically significant., Results: In OSCC study group, MUC1-positive immunoreaction was observed in 21 (70%) cases out of 30. All the samples in control group were negative for MUC1 immunoexpression. The immunohistochemical expression of MUC1 in OSCC group was statistically significant when compared with normal control group, as P < 0.05 (Pearson's Chi-square)., Conclusions: MUC1 is a reliable biomarker for the diagnosis of OSCC, but further studies are required to prove its role in prognosis., Competing Interests: There are no conflicts of interest.

Background Following peripheral nerve chronic constriction injury, the accumulation of the α2δ-1 auxiliary subunit of voltage-gated Ca 2+ channels in primary afferent terminals contributes to the onset of neuropathic pain. Overexpression of α2δ-1 in Xenopus oocytes increases the opening properties of Ca v 1.2 L-type channels and allows Ca 2+ influx at physiological membrane potentials. We therefore posited that L-type channels play a role in neurotransmitter release in the superficial dorsal horn in the chronic constriction injury model of neuropathic pain. Results Whole-cell recording from lamina II neurons from rats, subject to sciatic chronic constriction injury, showed that the L-type Ca 2+ channel blocker, nitrendipine (2 µM) reduced the frequency of spontaneous excitatory postsynaptic currents. Nitrendipine had little or no effect on spontaneous excitatory postsynaptic current frequency in neurons from sham-operated animals. To determine whether α2δ-1 is involved in upregulating function of Ca v 1.2 L-type channels, we tested the effect of the α2δ-1 ligand, gabapentin (100 µM) on currents recorded from HEK293F cells expressing Ca v 1.2/β4/α2δ-1 channels and found a significant decrease in peak amplitude with no effect on control Ca v 1.2/β4/α2δ-3 expressing cells. In PC-12 cells, gabapentin also significantly reduced the endogenous dihydropyridine-sensitive calcium current. In lamina II, gabapentin reduced spontaneous excitatory postsynaptic current frequency in neurons from animals subject to chronic constriction injury but not in those from sham-operated animals. Intraperitoneal injection of 5 mg/kg nitrendipine increased paw withdrawal threshold in animals subject to chronic constriction injury. Conclusion We suggest that L-type channels show an increased contribution to synaptic transmission in lamina II dorsal horn following peripheral nerve injury. The effect of gabapentin on Cav1.2 via α2δ-1 may contribute to its anti-allodynic action.

Odontogenic tumours are lesions that occur solely within the oral cavity and are so named because of their origin from the odontogenic (i.e. tooth-forming) apparatus. Odontogenic tumours comprise a variety of lesions ranging from non-neoplastic tissue proliferations to benign or malignant neoplasms. However, controversies exist regarding the pathogenesis, categorisation and clinical and histological variations of these tumours. The recent 2017 World Health Organization classification of odontogenic tumours included new entities such as primordial odontogenic tumours, sclerosing odontogenic carcinomas and odontogenic carcinosarcomas, while eliminating several previously included entities like keratocystic odontogenic tumours and calcifying cystic odonogenic tumours. The aim of the present review article was to discuss controversies and recent concepts regarding odontogenic tumours so as to increase understanding of these lesions.