Powassan Virus Encephalitis After Tick Bite, Manitoba, Canada.

A case of Powassan encephalitis occurred in Manitoba, Canada, after the bite of a black-legged tick. Awareness of this emerging tickborne illness is needed because the number of vector tick species is growing. No specific treatment options exist, and cases with illness and death are high. Prevention is crucial.

Evaluation of adapted parent training for challenging behaviour in pre-school children with moderate to severe intellectual developmental disabilities: A randomised controlled trial.

OBJECTIVES: There is limited evidence on the effectiveness of parenting interventions to improve disruptive behaviour in children with intellectual developmental disabilities. This clinical trial evaluated whether an adapted group parenting intervention for preschool children with intellectual developmental disabilities who display challenging behaviour is superior to treatment as usual in England. STUDY DESIGN: 261 children aged 30-59 months with moderate to severe intellectual developmental disabilities and challenging behaviour were randomised to either the intervention (Stepping Stones Triple P) and treatment as usual or treatment as usual alone. The primary outcome was the parent-rated Child Behaviour Checklist at 52 weeks after randomisation. A health economic evaluation was also completed. RESULTS: We found no significant difference between arms on the primary outcome (mean difference -4.23; 95% CI: -9.99 to 1.53; p = 0.147). However, a subgroup analysis suggests the intervention was effective for participants randomised before the COVID-19 pandemic (mean difference -7.12; 95% CI: -13.44 to -0.81; p = 0.046). Furthermore, a complier average causal effects analysis (mean difference -11.53; 95% CI: -26.97 to 3.91; p = 0.143) suggests the intervention requires participants to receive a sufficient intervention dose. The intervention generated statistically significant cost savings (-£1,057.88; 95% CI -£3,218.6 to -£46.67) but the mean point estimate in Quality Adjusted Life Years was similar in both groups. CONCLUSION: This study did not find an effect of the intervention on reducing challenging behaviour, but this may have been influenced by problems with engagement. The intervention could be considered by services as an early intervention if families are supported to attend, especially given its low cost.

A case series analysis of spigelian hernia: A diagnostic dilemma and its successful laparoscopic repair.

ABSTRACT: A Spigelian hernia is an uncommon, atypical protrusion of the peritoneum or abdominal contents via a defect (Spigelian fascia), consisting of the internal oblique aponeuroses and the transversus abdominis. With a frequency ranging from 0.12% to 2% of all abdominal wall hernias, Spigelian hernias are extremely rare. It usually arises from a condition that increases intra-abdominal pressure, the degeneration of the abdominal aponeurotic layers or trauma to the abdominal wall. Herein, we present a case series of patients with varying presentations of Spigelian hernia who presented, who were promptly diagnosed and who were managed successfully with laparoscopic surgical repair.

Comprehensive assessment of per and polyfluoroalkyl substances (PFAS) contamination in groundwater of Kamrup, Assam, India: occurrence, health risks, and metabolomic insights.

Per-and polyfluoroalkyl substances (PFAS) are synthetic chemicals that are known for their environmental persistence and adverse health effects. This study comprehensively assessed PFAS contamination in the Kamrup region of Assam, India, focusing on its presence in groundwater and associated health risks. The analysis detected 12 PFAS in groundwater samples from both the Kamrup Metro and Rural regions. In Kamrup Rural, Perfluorohexanoic acid (PFHxA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonic acid (PFOS) were prevalent, whereas in Kamrup Metro, PFNA and PFOS were dominant, based on detection frequencies. These findings are noteworthy, as they demonstrate the widespread presence of PFAS in groundwater, a vital source of drinking water in the region. The assessment of PFAS health risks in India involved hazard quotient calculations for different age groups. Perfluorobutanesulfonic acid (PFBS) posed the highest risk, ranking children > boys > men > girls > women. Overall, ∑PFAS had low hazard (HQ: 0.27-0.41). Further, this study assessed PFBS and PFOS toxicity in human kidney epithelial cell lines (HEK293T) cells, revealing that PFBS was more cytotoxic than PFOS. The study examined the metabolomics of HEK293T cells after PFBS exposure, revealing significant alterations in lipid metabolism, particularly glycerophospholipids, potentially affecting cellular function and health. These findings underscore the importance of monitoring PFAS contamination in drinking water sources, especially in regions such as Kamrup, where groundwater is a primary source. Our metabolomics results show significant health effects at the cellular level, raising concerns about the impact of PFAS exposure on human health. This study highlights PFAS contamination in Kamrup, Assam's groundwater and its health risks, providing valuable insights for policymakers and public health management.

Coping strategies in young people during the COVID-19 pandemic: rapid review.

AIMS AND METHOD: To better understand factors supporting young people's (age <18 years) mental health during pandemic-type conditions, we aimed to identify whether coping strategies adopted during the COVID-19 pandemic could be dichotomised according to manifesting positive or negative psychological outcomes. Medline, EMBASE, CINAHL, PsycINFO, Scopus and ASSIA databases were used to identify empirical studies that examined coping strategies used by young people experiencing psychological challenges during COVID-19. RESULTS: Twenty-five international studies were included, identifying that coping strategies adopted could be significantly dichotomised according to reducing or exacerbating psychological challenges. Positive coping strategies were proactive and solutions-oriented, whereas negative coping strategies were more avoidant and emotion-oriented. CLINICAL IMPLICATIONS: An internal locus of control may account for why adolescents exercised more proactive coping compared with their younger counterparts, although parents of younger children may offset the impact of stressors by drawing on a proposed coping framework emphasising proactivity and engagement. This would be an invaluable addition to future pandemic preparedness planning cycles.

Phantom Hernia: A Rare Sequela of Herpes Zoster Infection.

The herpes zoster (HZ) virus first manifests as varicella, or chickenpox, in children and remains dormant in the dorsal root ganglia of the nerves. The vesicular eruptions that might be painful develop along a dermatome when the virus is reactivated. While postherpetic neuralgia is a well-known side effect of herpes simplex, there are well-reported motor consequences as well. Segmental zoster paresis is an uncommon motor consequence of herpes zoster that resembles an anterior abdominal wall hernia but does not require surgery in contrast to an actual abdominal wall hernia. We present a similar case of a 46-year-old male who presented with classic herpes zoster rash and phantom hernia as a rare sequela of this condition.

Evaluation of Gemcitabine and Epigallocatechin-3-Gallate Loaded Solid Lipid Nanoparticles on Benzopyrene Induced Lung Cancer Model Via Intranasal Route: Improved Pharmacokinetics and Safety Profile.

The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.

Beyond biopsy for neurosarcoidosis: A review of blood and CSF biomarkers.

Neurosarcoidosis, a rare granulomatous disease, causes inflammation and damage to the central nervous system (CNS). A major diagnostic challenge in neurosarcoidosis is the absence of well-defined biomarkers. The need for biopsy to make the diagnosis can lead to delays and misdiagnosis if histopathology is inaccessible or indeterminate, highlighting the need for more accessible diagnostic indicators. The current gold standard for a "definite" neurosarcoidosis diagnosis requires biopsy of CNS tissue revealing non-caseating granulomas. However, such biopsies are inherently invasive and carry associated procedural risks. Notably, angiotensin-converting enzyme (ACE), commonly associated with systemic sarcoidosis, is recognized as a poor biomarker for neurosarcoidosis due to its lack of accuracy in the context of CNS involvement. Furthermore, imaging in neurosarcoidosis, while widely utilized and important for narrowing the diagnosis, lacks specificity. Decades of research have yielded molecular and immunologic biomarkers-soluble interleukin-2 receptor (IL-2R), serum amyloid A1, the CD4/CD8 ratio, neopterin, interferon-gamma (IFN-γ), and chemokine ligand 2 (CCL2)-that hold potential for improving diagnostic accuracy. However, these biomarkers are not yet established in clinical care as they may be difficult to obtain and are derived from small studies. They also suffer from a lack of specificity against other inflammatory and infectious central nervous system diseases. New biomarkers are needed for use alongside those previously discovered to improve diagnosis of this rare disease. This review synthesizes existing literature on neurosarcoidosis biomarkers, aiming to establish a foundation for further research in this evolving field. It also consolidates information on biomarkers of systemic sarcoidosis such as IL-8 and soluble CD40L that have not yet been studied in neurosarcoidosis but hold potential as markers of CNS disease.

Artificial intelligence for cardiovascular disease risk assessment in personalised framework: a scoping review.

Background: The field of precision medicine endeavors to transform the healthcare industry by advancing individualised strategies for diagnosis, treatment modalities, and predictive assessments. This is achieved by utilizing extensive multidimensional biological datasets encompassing diverse components, such as an individual's genetic makeup, functional attributes, and environmental influences. Artificial intelligence (AI) systems, namely machine learning (ML) and deep learning (DL), have exhibited remarkable efficacy in predicting the potential occurrence of specific cancers and cardiovascular diseases (CVD). Methods: We conducted a comprehensive scoping review guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Our search strategy involved combining key terms related to CVD and AI using the Boolean operator AND. In August 2023, we conducted an extensive search across reputable scholarly databases including Google Scholar, PubMed, IEEE Xplore, ScienceDirect, Web of Science, and arXiv to gather relevant academic literature on personalised medicine for CVD. Subsequently, in January 2024, we extended our search to include internet search engines such as Google and various CVD websites. These searches were further updated in March 2024. Additionally, we reviewed the reference lists of the final selected research articles to identify any additional relevant literature. Findings: A total of 2307 records were identified during the process of conducting the study, consisting of 564 entries from external sites like arXiv and 1743 records found through database searching. After 430 duplicate articles were eliminated, 1877 items that remained were screened for relevancy. In this stage, 1241 articles remained for additional review after 158 irrelevant articles and 478 articles with insufficient data were removed. 355 articles were eliminated for being inaccessible, 726 for being written in a language other than English, and 281 for not having undergone peer review. Consequently, 121 studies were deemed suitable for inclusion in the qualitative synthesis. At the intersection of CVD, AI, and precision medicine, we found important scientific findings in our scoping review. Intricate pattern extraction from large, complicated genetic datasets is a skill that AI algorithms excel at, allowing for accurate disease diagnosis and CVD risk prediction. Furthermore, these investigations have uncovered unique genetic biomarkers linked to CVD, providing insight into the workings of the disease and possible treatment avenues. The construction of more precise predictive models and personalised treatment plans based on the genetic profiles of individual patients has been made possible by the revolutionary advancement of CVD risk assessment through the integration of AI and genomics. Interpretation: The systematic methodology employed ensured the thorough examination of available literature and the inclusion of relevant studies, contributing to the robustness and reliability of the study's findings. Our analysis stresses a crucial point in terms of the adaptability and versatility of AI solutions. AI algorithms designed in non-CVD domains such as in oncology, often include ideas and tactics that might be modified to address cardiovascular problems. Funding: No funding received.

Current Management of Neuroendocrine Tumour Liver Metastases.

PURPOSE OF REVIEW: This article aims to illustrate the current state of investigations and management of liver metastases in patients with Neuroendocrine Neoplasms. Neuroendocrine tumours (NETs) are rising in incidence globally and have become the second most prevalent gastrointestinal malignancy in UK and USA. Frequently, patients have metastatic disease at time of presentation. The liver is the most common site of metastases for gastro-enteropancreatic NETs. Characterisation of liver metastases with imaging is important to ensure disease is not under-staged. RECENT FINDINGS: Magnetic resonance imaging and positron emission tomography are now becoming standard of care for imaging liver metastases. There is an increasing armamentarium of therapies available for management of NETs and loco-regional therapy for liver metastases. The data supporting surgical and loco-regional therapy is reviewed with focus on role of liver transplantation. It is important to use appropriate imaging and classification of NET liver metastases. It is key that decisions regarding approach to treatment is undertaken in a multidisciplinary team and that individualised approaches are considered for management of patients with metastatic NETs.

An Incidental Finding of Unilateral Winged Scapula in a Patient Presenting With Acute Abdomen: A Case Report.

The primary cause of scapular winging, also known as scapula alata, is typically a malfunction of the serratus anterior, trapezius, and rhomboids, the three major scapular stabilizers. Scapular winging is often caused by injuries to the long thoracic nerve, which weakens the serratus anterior muscle. The long thoracic nerve is particularly vulnerable to both acute and nontraumatic damage due to its longer and superficial course. There are very few documented cases of isolated scapula winging. Here, we present the case of a 15-year-old Asian female who initially presented with right hypochondrium pain, and during a general physical examination, an incidental finding of a left-winged scapula was noted.

A Study on the Epidemiology of COVID-19-Related Guillain-Barré Syndrome in the United States.

INTRODUCTION: Several neurological complications have been reported with COVID-19, including Guillain-Barré syndrome (GBS). We looked at incidence, baseline characteristics, and in-hospital outcomes of COVID-19-associated GBS in the United States. STUDY DESIGN AND METHODS: We conducted a retrospective analysis using the US National Inpatient Sample database to identify hospitalizations for COVID-19 and GBS, using International Classification of Disease, 10th Revision, codes G610 and G650 for GBS and U071 for COVID-19. The codes used in this study are listed in Supplemental Digital Content 1 (see e Appendix, http://links.lww.com/JCND/A69). RESULTS: In total, 13,705 GBS admissions were recorded nationwide in 2020; of these, 1155 (8.43%) were associated with COVID-19. The frequency of GBS in COVID-19 admissions was 0.07%, compared with 0.08% in non-COVID-19 admissions (P = 0.8166). COVID-19 cohort with GBS had higher utilization of invasive mechanical ventilation (20.8% vs. 11.8%, P < 0.001) in comparison with COVID-19 cohort without GBS. GBS admissions with COVID-19 exhibited significantly higher inpatient mortality (12.2% vs. 3%, P < 0.001) compared with GBS admissions without COVID-19. INTERPRETATION: Our findings underscore GBS as a rare yet severe complication of COVID-19, highlighting a significant difference in mortality when compared with GBS not associated with COVID-19.

Epidemiology and Outcomes of Hospitalized Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Patients Who Developed Acute Respiratory Failure.

Objectives:The aim of the study was to examine the incidence, baseline characteristics, and outcomes of Chimeric Antigen Receptor T-cell (CAR-T) therapy admissions in individuals who developed acute respiratory failure (ARF). The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020. Methods: The study identified CAR-T cell therapy hospitalizations through the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. Patients with acute respiratory failure (ARF) were further classified using specific International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Descriptive statistics were performed to analyze baseline characteristics, comorbidities, complications, and outcomes. Results: Analysis of the NIS Database identified 5545 CAR-T therapy admissions between 2017 and 2020, revealing a rising trend over time. In our study, we found that hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were the most frequently observed comorbidities in CAR-T cell therapy admissions. Acute respiratory failure (ARF) was reported in 7.1% of admissions, and they had higher all-cause in-hospital mortality than CAR-T cell therapy admissions without ARF (32.9% vs 1.3%, P < 0.001). ARF admissions that required invasive mechanical ventilation (IMV) also had higher all-cause in-hospital mortality compared to admissions not requiring IMV (48.9% vs 11.8%, P = 0.001). There was no difference in the mortality rate among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that utilized CAR-T therapy. Conclusions: In this largest study to date, we illuminate the incidence and outcomes of CAR-T cell therapy admissions with ARF. Higher mortality rates were observed in CAR-T cell therapy admissions with ARF. The study emphasizes the crucial role of interdisciplinary collaboration in CAR-T patient management and calls for additional research to clarify ARF's etiology and inform effective management strategies.

Engineering CRISPR/Cas9 therapeutics for cancer precision medicine.

The discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) technology has revolutionized field of cancer treatment. This review explores usage of CRISPR/Cas9 for editing and investigating genes involved in human carcinogenesis. It provides insights into the development of CRISPR as a genetic tool. Also, it explores recent developments and tools available in designing CRISPR/Cas9 systems for targeting oncogenic genes for cancer treatment. Further, we delve into an overview of cancer biology, highlighting key genetic alterations and signaling pathways whose deletion prevents malignancies. This fundamental knowledge enables a deeper understanding of how CRISPR/Cas9 can be tailored to address specific genetic aberrations and offer personalized therapeutic approaches. In this review, we showcase studies and preclinical trials that show the utility of CRISPR/Cas9 in disrupting oncogenic targets, modulating tumor microenvironment and increasing the efficiency of available anti treatments. It also provides insight into the use of CRISPR high throughput screens for cancer biomarker identifications and CRISPR based screening for drug discovery. In conclusion, this review offers an overview of exciting developments in engineering CRISPR/Cas9 therapeutics for cancer treatment and highlights the transformative potential of CRISPR for innovation and effective cancer treatments.

Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting.

Introduction: The prognostic significance of steroid receptors in bladder cancer remains controversial. This study was designed to determine the expression status of androgen receptor (AR), estrogen receptors (ERα and Erß), and its potential role in predicting survival in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Sixty patients of NMIBC were screened and 57 (41 males and 16 females) were included in our study. The tissue microarray slides were evaluated by pathologists blinded to the clinical information. Association of distribution of steroid receptors with stage, grade, progression, and recurrence was seen. Results: The mean age of the population was 60.9 ± 9.3 years. Pathologically, majority of the patients were Ta (Ta: T1 stage 61.4% vs. 38.6%). Nine (15.8%) of the tumors stained positive for AR while one (1.8%) tumor stained positive for ERα and 36 (63.2%) tumors stained for ERß. A higher proportion of male NMIBC stained positive for AR (19.5% vs. 6.2%, P = 0.420) while ERß positivity was higher in females (58.5% vs. and 75%,P = 0.247). AR-negative tumors showed higher recurrence (20/48%-42%) as compared to AR-positive tumors (2/9%-22%). ERß-positive tumors showed higher recurrence (15/36%-42% vs. 7/21%-33%, P = 0.179). Progression-free survival (PFS) was found to be significantly lower for ERß-negative group (log-rank test P = 0.035). Conclusion: AR and ERß positivity is found in NMIBC patients while ERα shows minimal staining in NMIBC patients. Although it did not reach a statistical significance, a higher proportion of AR-negative and ERß-positive tumors recurred as compared to AR-positive and ERß-negative patients. PFS was significantly lower in ERß-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.

The development of the Helping your Anxious Child programme: a parent-mediated group intervention for parents of autistic children in South Asia.

Autistic children are at increased risk of experiencing a range of mental health difficulties, including anxiety. A number of intervention programmes are now available in high-income countries to support autistic children. However, to date there are no evidence-based interventions to support families of such children in South Asia. Based on consultations with clinicians, researchers and parents in Bangladesh and Sri Lanka, we developed a culturally tailored two-session skills-based group programme for parents whose autistic children present with anxiety. This paper describes the process of creating this programme, to be delivered by mental health professionals.

Deep learning approach for cardiovascular disease risk stratification and survival analysis on a Canadian cohort.

The quantification of carotid plaque has been routinely used to predict cardiovascular risk in cardiovascular disease (CVD) and coronary artery disease (CAD). To determine how well carotid plaque features predict the likelihood of CAD and cardiovascular (CV) events using deep learning (DL) and compare against the machine learning (ML) paradigm. The participants in this study consisted of 459 individuals who had undergone coronary angiography, contrast-enhanced ultrasonography, and focused carotid B-mode ultrasound. Each patient was tracked for thirty days. The measurements on these patients consisted of maximum plaque height (MPH), total plaque area (TPA), carotid intima-media thickness (cIMT), and intraplaque neovascularization (IPN). CAD risk and CV event stratification were performed by applying eight types of DL-based models. Univariate and multivariate analysis was also conducted to predict the most significant risk predictors. The DL's model effectiveness was evaluated by the area-under-the-curve measurement while the CV event prediction was evaluated using the Cox proportional hazard model (CPHM) and compared against the DL-based concordance index (c-index). IPN showed a substantial ability to predict CV events (p < 0.0001). The best DL system improved by 21% (0.929 vs. 0.762) over the best ML system. DL-based CV event prediction showed a ~ 17% increase in DL-based c-index compared to the CPHM (0.86 vs. 0.73). CAD and CV incidents were linked to IPN and carotid imaging characteristics. For survival analysis and CAD prediction, the DL-based system performs superior to ML-based models.

Low absolute risk of thrombotic and cardiovascular events in outpatient pregnant women with COVID-19.

INTRODUCTION: Pregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events. MATERIALS & METHODS: We analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and for men ≤45 years, as points of reference. RESULTS: Among 6585 outpatients, 169 were pregnant at diagnosis. By 90-day follow-up, two pregnant women during the third trimester had lower extremity venous thrombosis, one deep and one superficial vein thrombosis. The cumulative incidence of thrombotic events was 1.20 % (95 % confidence interval [CI]: 0.0 to 2.84 %). Respective rates were 0.47 % (95 % CI: 0.14 % to 0.79 %) among non-pregnant women, and 0.49 % (95 % CI: 0.06 % to 0.91 %) among men ≤45 years. No non-thrombotic cardiovascular events occurred in pregnant women. The rates of cardiovascular events were 0.53 % (95 % CI: 0.18 to 0.87) among non-pregnant women, and 0.68 % (95 % CI: 0.18 to 1.18) in men aged ≤45 years. CONCLUSIONS: Thrombotic and cardiovascular events are rare among outpatients with COVID-19. Although a higher event rate among outpatient pregnant women cannot be excluded, the absolute event rates are low and do not warrant population-wide cardiovascular interventions to optimize outcomes.