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Summary: Glial-vascular interactions are critical for the formation and maintenance of brain blood vessels and the blood-brain barrier (BBB) in mammals, but their role in the zebrafish BBB remains unclear. Using three glial gene promoters—gfap, glast, and glastini (a truncated glast)—we explored glial-vascular development in zebrafish. Sparse labeling showed fewer glial-vascular interactions at early stages, with glial coverage and contact area increasing with age. Stable transgenic lines for glast and glastini revealed similar developmental increases, starting at ∼30% coverage at 3 days post-fertilization (dpf) and peaking at ∼60% by 10 dpf, and consistently higher glial coverage in the forebrain and midbrain than in the hindbrain. Electron microscopy analyses showed similar progressive increases in glial-vascular interactions, with maximal coverage of ∼70% in adults—significantly lower than the ∼100% seen in mammals. These findings define the temporal and regional maturation of glial-vascular interactions in zebrafish and highlight differences from mammalian systems.

Abstract Background A sizeable proportion of pathogenic genetic variants identified in young children tested for congenital differences are associated with neurodevelopmental psychiatric disorders (NPD). In this growing group, a genetic diagnosis often precedes the emergence of diagnosable developmental concerns. Here, we describe DAGSY (Developmental Assessment of Genetically Susceptible Youth), a novel interdisciplinary ‘genetic-diagnosis-first’ clinic integrating psychiatric, psychological and genetic expertise, and report our first observations and feedback from families and referring clinicians. Methods We retrieved data on referral sources and indications, genetic and NPD diagnoses and recommendations for children seen at DAGSY between 2018 and 2022. Through a survey, we obtained feedback from twenty families and eleven referring clinicians. Results 159 children (mean age 10.2 years, 57.2% males) completed an interdisciplinary (psychiatry, psychology, genetic counselling) DAGSY assessment during this period. Of these, 69.8% had a pathogenic microdeletion or microduplication, 21.5% a sequence-level variant, 4.4% a chromosomal disorder, and 4.4% a variant of unknown significance with emerging evidence of pathogenicity. One in four children did not have a prior NPD diagnosis, and referral to DAGSY was motivated by their genetic vulnerability alone. Following assessment, 76.7% received at least one new NPD diagnosis, most frequently intellectual disability (24.5%), anxiety (20.7%), autism spectrum (18.9%) and specific learning (16.4%) disorder. Both families and clinicians responding to our survey expressed satisfaction, but also highlighted some areas for potential improvement. Conclusions DAGSY addresses an unmet clinical need for children identified with genetic variants that confer increased vulnerability for NPD and provides a crucial platform for research in this area. DAGSY can serve as a model for interdisciplinary clinics integrating child psychiatry, psychology and genetics, addressing both clinical and research needs for this emerging population.

The healthcare industry is exponentially growing its dependence on smart wearables and remote devices for efficient treatment and diagnosis. These smart devices benefit the healthcare industry, but they raise serious security and integrity concerns while exchanging healthcare data. These devices are primarily meant for data dissemination; hence, they are equipped with weak security protocols that are susceptible to attacks like distributed denial-of-service (DDoS), data injection, and man-in-the-middle (MiTM) attacks. To circumvent the aforementioned security challenges, this article proposed a secure and intelligent data exchange framework for smart healthcare systems. For that, we amalgamate artificial intelligence (AI) and blockchain technology to strengthen the security of data dissemination between smart medical devices. Further, we adopted fuzzy logic that extracts the essential features from the healthcare security dataset to enhance the detection rate of AI models. We used different AI algorithms such as logistic regression (LR), random forest (RF), decision trees (DT), stochastic gradient descent (SGD), and Gaussian naive Bayes (GNB) to classify healthcare data into malicious and non-malicious. The predicted data can still be maneuvered by adversaries that introduce subtle changes that skew the results to their advantage. Therefore, we employed blockchain technology that stores non-malicious healthcare data (predicted data) from data tampering attacks. The developed smart contract validates the non-malicious healthcare data and only allows them to be securely stored inside the interplanetary file system (IPFS)-based public blockchain. The proposed framework is evaluated by considering various evaluation metrics like recall, precision, accuracy, F1 score, area under the curve (AUC) score, and blockchain scalability.

Aim and background: A significant proportion of hypertensive patients do not achieve good blood pressure (BP) control despite optimal medications and salt restriction. Considering the BP-lowering effect of magnesium reported in some previous studies, we wanted to assess the correlation between magnesium intake and control of BP in Indian hypertensives. Twenty-four-hour urinary magnesium excretion was used as a surrogate marker of magnesium intake. Further, the effect of supplementation of magnesium-rich flaxseeds on control of BP was assessed, in a subset of the study subjects. Methodology: In this case-control study, 40 patients of essential hypertension with poor BP control as per JNC-8 BP goals were enrolled as cases and 40 patients of essential hypertension with good BP control were enrolled as controls. Twenty-four-hour urinary samples were collected in both cases and controls and urinary magnesium-creatinine (Mg/Cr) ratios were estimated. The urinary Mg/Cr ratios of patients of the two groups were compared using the Mann–Whitney U test. A subset of 23 patients was given an intervention of three tablespoons of roasted whole flaxseeds daily for 4 weeks, and the significance of the change in mean BP, before and after the intervention, was assessed using a paired t-test. Results: The urinary Mg/Cr ratio in the good BP-control group [median = 77.05 [interquartile range (IQR)] = 23.51–101.80] was higher, compared to the poor BP-control group [median = 56.49 (IQR = 44.19–69.97)], with p-value = 0.02852, when tested with Mann–Whitney U test. In the subset of consenting participants, who took 3 Tbsp flax seeds daily, the average systolic BP and diastolic BP decreased significantly, from 141.13 (SD = 11) mm Hg and 87.65 (SD = 9.19) mm Hg to 134.22 (SD = 11.50) mm Hg and 84.65 (SD = 8.17) mm Hg, respectively (Paired t-test; p-value for SBP = 0.005, DBP = 0.013). Conclusion: Hypertensive patients with good BP control have higher levels of 24-hour urinary magnesium excretion when compared to patients with poor BP control. Flaxseeds can be used in hypertensive patients as an adjuvant to drug therapy to improve BP control. Clinical significance: Hypertensive patients can be advised to consume flax seeds regularly to maintain healthy magnesium levels and control hypertension.

Background: Over 296 million people worldwide are living with chronic Hepatitis B (CHB) infection who require monitoring of viral activity and disease progression. Serum HBV RNA is a promising new biomarker in CHB management. No standardized method for serum HBV RNA quantification has been established. Objectives: To develop and validate, both analytically and clinically, a 3′ RACE RT-qPCR assay for quantification of serum HBV RNA. Study design: The 3′ RACE RT-qPCR method was developed using published primers. The analytical limit of detection and quantification, linearity, inter- and intra-assay repeatability, and clinical specificity and sensitivity were evaluated using synthetic pre-genomic RNA and specimens from various patient populations. Intra- and inter-laboratory ring trials involving three laboratories were completed. Results: The 3′ RACE RT-qPCR assay dynamic range is 25 to 108 copies/µL of synthetic RNA. Theoretical and measured serum HBV RNA quantities from a serially diluted sample showed excellent linearity (R2=0.9795). The inter- and intra-assay repeatability were 94.91% and 95.12%, respectively. Clinical specificity and sensitivity were 100% and 90%, respectively, in treated patients. Inter-laboratory analysis demonstrated moderate to high agreement among participating laboratories (κ = 0.581 to 0.867). High agreement was also observed between both operators participating in the intra-laboratory evaluation (κ = 0.867). Conclusions: Our methodology for the quantification of serum HBV RNA is specific and repeatable and employs a biologically relevant RNA standard suitable for medium throughput laboratories. Method standardization is required to facilitate the comparison of studies and better understand the clinical role of this novel biomarker.

Precision medicine has greatly aided in improving health outcomes using earlier diagnosis and better prognosis for chronic diseases. It makes use of clinical data associated with the patient as well as their multi-omics/genomic data to reach a conclusion regarding how a physician should proceed with a specific treatment. Compared to the symptom-driven approach in medicine, precision medicine considers the critical fact that all patients do not react to the same treatment or medication in the same way. When considering the intersection of traditionally distinct arenas of medicine, that is, artificial intelligence, healthcare, clinical genomics, and pharmacogenomics—what ties them together is their impact on the development of precision medicine as a field and how they each contribute to patient-specific, rather than symptom-specific patient outcomes. This study discusses the impact and integration of these different fields in the scope of precision medicine and how they can be used in preventing and predicting acute or chronic diseases. Additionally, this study also discusses the advantages as well as the current challenges associated with artificial intelligence, healthcare, clinical genomics, and pharmacogenomics.

In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery.

This article presents a method for extracting high-level semantic information through successful landmark detection using 2D RGB images. In particular, the focus is placed on the presence of particular labels (open path, humans, staircase, doorways, obstacles) in the encountered scene, which can be a fundamental source of information enhancing scene understanding and paving the path towards the safe navigation of the mobile unit. Experiments are conducted using a manual wheelchair to gather image instances from four indoor academic environments consisting of multiple labels. Afterwards, the fine-tuning of a pretrained vision transformer (ViT) is conducted, and the performance is evaluated through an ablation study versus well-established state-of-the-art deep architectures for image classification such as ResNet. Results show that the fine-tuned ViT outperforms all other deep convolutional architectures while achieving satisfactory levels of generalization.

Pancreatitis usually presents with characteristic abdominal pain, radiological findings, and elevated lipase. The presence of jaundice may hint at a biliary etiology; however, it is not always present. We hypothesized that the presence of jaundice is associated with worse outcomes in patients admitted with pancreatitis. We conducted a retrospective analysis using the National Inpatient Sample, inquiring about patients admitted with pancreatitis with and without jaundice between October 2015 and December 2017. The primary outcome was in-hospital mortality in patients admitted for pancreatitis with and without jaundice. Secondary outcomes were the median length of stay, hospitalization cost, the incidence of ventilator-dependent respiratory failure (VDRF), acute respiratory distress syndrome (ARDS), sepsis, septic shock, dehydration and electrolyte disturbances, and ascites. A total of 1,267,744 patients were admitted with pancreatitis from October 2015 to December 2017. Among them, 8855 (0.7%) had concomitant jaundice on presentation. In-hospital mortality in this group was 4.3%. The patients with pancreatitis and jaundice had higher odds of in-hospital mortality (adjusted odds ratio [aOR]: 1.51, 99% CI 1.35–1.68, p

During 2014, cutaneous lesions were reported in dairy cattle and farmworkers in the Amazon Region of western Colombia. Samples from 6 patients were analyzed by serologic and PCR testing, and results demonstrated the presence of vaccinia virus and pseudocowpox virus. These findings highlight the need for increased poxvirus surveillance in Colombia.

The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today’s populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios. In addition to concerns about preparedness for a potential malevolent reintroduction of variola virus, humans are becoming increasingly exposed to naturally occurring zoonotic orthopoxviruses and, following these exposures, disease severity is worse in individuals who never received smallpox vaccination. This study investigated whether postexposure vaccination of prairie dogs with 2nd and 3rd generation smallpox vaccines was protective against monkeypox disease in four exposure scenarios. We infected animals with monkeypox virus at doses of 104 pfu (2× LD50) or 106 pfu (170× LD50) and vaccinated the animals with IMVAMUNE® or ACAM2000® either 1 or 3 days after challenge. Our results indicated that postexposure vaccination protected the animals to some degree from the 2× LD50, but not the 170× LD5 challenge. In the 2× LD50 challenge, we also observed that administration of vaccine at 1 day was more effective than administration at 3 days postexposure for IMVAMUNE®, but ACAM2000® was similarly effective at either postexposure vaccination time-point. The effects of postexposure vaccination and correlations with survival of total and neutralizing antibody responses, protein targets, take formation, weight loss, rash burden, and viral DNA are also presented.

Introduction: Medical educators in recent years have been using social media for more penetrance to technologically-savvy learners. The utility of using Twitter for curriculum content delivery has not been studied. We sought to determine if participation in a social media-based educational supplement would improve student performance on a test of clinical images at the end of the semester. Methods: 116 second-year medical students were enrolled in a lecture-based clinical medicine course, in which images of common clinical exam findings were presented. An additional, optional assessment was performed on Twitter. Each week, a clinical presentation and physical exam image (not covered in course lectures) were distributed via Twitter, and students were invited to guess the exam finding or diagnosis. After the completion of the course, students were asked to participate in a slideshow “quiz” with 24 clinical images, half from lecture and half from Twitter. Results: We conducted a one-way analysis of variance to determine the effect Twitter participation had on total, Twitter-only, and lecture-only scores. Twitter participation data was collected from the end-of-course survey and was defined as submitting answers to the Twitter-only questions “all or most of the time”, “about half of the time”, and “little or none of the time.” We found a significant difference in overall scores (p

Currently, a number of assays measure Orthopoxvirus neutralization with serum from individuals, vaccinated against smallpox. In addition to the traditional plaque reduction neutralization test (PRNT), newer higher throughput assays are based on neutralization of recombinant vaccinia virus, expressing reporter genes such as β-galactosidase or green fluorescent protein. These methods could not be used to evaluate neutralization of variola virus, since genetic manipulations of this virus are prohibited by international agreements. Currently, PRNT is the assay of choice to measure neutralization of variola virus. However, PRNT assays are time consuming, labor intensive, and require considerable volume of serum sample for testing. Here, we describe the development of a high-throughput, cell-based imaging assay that can be used to measure neutralization, and characterize replication kinetics of various Orthopoxviruses, including variola, vaccinia, monkeypox, and cowpox.

The study was carried out to assess effectiveness of planned teaching programme on knowledge regarding palliative care among staff nurses. Convenient sampling was used to select 150 staff nurses from selected hospitals, Anand. The questionnaire consisted of demographic data of the participants and knowledge questionnaire on palliative care. Lesson plan was developed with the help of subject experts. Pre-test was administered on the first day and planned teaching programme was executed on the same day. The post-test had been taken after 7 days of pre-test. Results: Data was analyzed using IBM SPSS Statistics 20. The findings of the study revealed that there was a significant difference found between pre and post test knowledge score t-29.5(p 0.00), hence the planned teaching programme was effective in improving nurse's knowledge. Conclusions: As palliative care is an important aspect of nursing care, nurses need to be educated on palliative care and informed about changes that are happening in this area. [ABSTRACT FROM AUTHOR]

Introduction: Vestibular dysfunction is either unilateral or bilateral. These depict similar signs and symptoms. Here patient primarily complains of head movement induced dizziness and imbalance. The present study compared the customized vestibular rehabilitation therapy (VRT) in unilateral and bilateral vestibular lesion patients. Method: The subjects were assigned into two groups by purposive sampling (n=10 each). Group A was Unilateral and group B was Bilateral Vestibular Lesion. Both were given customized vestibular rehabilitation therapy. The twelve days protocol included gaze stability (two mins), dizziness (thirty secs hold, three repetitions) and balance improvement progression exercises (five repetitions each) with thirty secs rest interval in between. Student t test was used for analysis. Patients were evaluated for dizziness and risk of fall using Dizziness Handicap Inventory (DHI) and Fall Efficacy Scale (FES). For the assessment of balance, Tandem Walk, Limit of Stability and Clinical Test of Sensory Interaction on Balance (CTSIB) sub-parameters were evaluated using Balance Master. Result: The vestibular rehabilitation therapy was effective for functional domain of dizziness and FES in both unilateral and bilateral lesion patients. In unilateral lesion patients even physical domain of dizziness, reaction time (RT), end point excursion (EPE) and directional velocity (DCL), sub-parameters of limit of stability and step width, speed, end sway sub-parameters of tandem gait also improved. In bilateral vestibular lesion, only the sway velocity in CTSIB showed improvement. Conclusion: Customized Vestibular Rehabilitation Therapy was effective in improving dizziness and risk of fall greater than balance in unilateral and bilateral vestibular lesion patients. [ABSTRACT FROM AUTHOR]

Hepatorenal syndrome (HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation (LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant (SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS. Unfortunately, even after aggressive measures such as terlipressin use, the rate of recovery is less than 50% of patients. Moreover, current SLKT guidelines include: (1) estimation of glomerular filtration rate of 30 mL/min or less for 4-8 wk; (2) proteinuria > 2 g/d; or (3) biopsy proven interstitial fibrosis or glomerulosclerosis. Even with these updated criteria there is a lack of consistency regarding long-term benefits for SLKT vs LT alone. Finally, in regards to kidney dysfunction in the post-transplant setting, an estimation of glomerular filtration rate < 60 mL/min per 1.73 m(2) may be associated with an increased risk of patients having long-term end stage renal disease. HRS is common in patients with cirrhosis and those on liver transplant waitlist. Prompt identification and therapy initiation in transplant candidates with HRS may improve post-transplantation outcomes. Future studies identifying optimal vasoconstrictor regimens, alternative therapies, and factors predictive of response to therapy are needed. The appropriate use of SLKT in patients with HRS remains controversial and requires further evidence by the transplant community.