Renal artery occlusion in a young woman - a tale of mysterious thrombosis.

BACKGROUND: Renal artery thrombosis is rare and limited reports exist in the young population. The most common aetiology is thromboembolic disease or abdominal trauma in this population and isolated occurrences are extremely rare. We present the case of an 18-year-old woman with spontaneous unilateral renal artery thrombosis and infarction for whom reperfusion was achieved through endovascular intervention. The aetiology of her thrombosis remains unclear and is under investigation with differential diagnoses being fibromuscular dysplasia, large and medium vessel vasculitis, and thromboembolic causes. OBJECTIVE: To demonstrate the value in attempting salvage of an ischaemic kidney in a young patient with an unexplained spontaneous renal thrombosis. METHOD: JM is an 18-year-old woman who presented to a large regional tertiary hospital with 3 days of right flank pain. She had no infective symptoms and no urinary or bowel changes before admission. She was not pregnant, and her only medication was the oral contraceptive pill commenced 3 months prior. A CT angiogram demonstrated right renal artery thrombosis with renal infarction. The kidney was deemed potentially salvageable, and ultrasound defined adequate vessel calibre to access for thrombectomy in the context of a negative coagulopathy screen. RESULTS: The patient underwent thrombolysis, thrombectomy and balloon angioplasty. Intraoperatively, a thin segment of distal stenosis was identified, and angiogram reperfusion was achieved with subsequent improvement in renal function. CONCLUSION: Renal artery thrombosis in young people is extremely rare and presents a diagnostic and management challenge requiring input from multiple teams including nephrology, rheumatology, paediatrics and vascular surgery. Systemic coagulopathy and vasculitis are differentials against anatomical aetiologies such as fibromuscular dysplasia. Our case adds to the limited literature regarding this in the young population. Renal artery thrombosis with occlusion in young people is very rare and is most often associated with a systemic coagulopathic disorder, such as antiphospholipid syndrome or structural pathology of the renal vasculature such as fibromuscular dysplasia. The work-up of a young female presenting with renal artery thrombosis without any previous medical history screens for a wide range of pathological processes.

Factors Influencing Social and Community Participation of People with Spinal Cord Injury in Karnataka, India.

Background: Social and community participation are major indicators to assess the adequacy of treatment and rehabilitation in patients with spinal cord injury (SCI). This study examined the relationship between functional independence, level of disability, and social and community participation among people with SCI in India. Materials and Method: In this cross sectional study, 110 persons with SCI, aged 18 years and above participated in a community setting, in Karnataka, India. Spinal Cord Independence Measure Version III-self-reporting (SCIM III-SR), Craig Handicap Assessment and Reporting Technique (CHART), and WHO Disability Assessment Schedule 2.0 (WHODAS) were the clinical outcome measures. Spearman's correlation and stepwise multiple linear regression were done to determine association and identify the factors determining the community participation of people with SCI. Results: CHART physical independence had a positive correlation with SCIM self-care (R = 0.446) and SCIM mobility (r = 0.434). CHART cognitive independence (R = -0.38) and CHART mobility (R = -0.396) had a weak correlation with WHODAS. SCIM self-care and SCIM mobility (R2 = 0.34) were determinants of CHART cognitive independence. SCIM respiratory and sphincter management and SCIM self-care (R2 = 0.327) were determinants of CHART mobility. Conclusion: Self-care and mobility of people with SCI determine their ability to successfully reintegrate into the community, warranting a comprehensive community rehabilitation program.

Assessing left atrial size and pump function in ischemic stroke patients: Is cardiac MRI superior to transthoracic echocardiography?

OBJECTIVES: Current guidelines recommend transthoracic echocardiography (TTE) following an ischemic stroke as the primary technique to identify cardiac abnormalities associated with an increased risk of cerebral embolism. It is unclear whether cardiac magnetic resonance imaging (cMRI), a technique shown to provide increased imaging resolution, may also enhance the cardiac assessment of ischemic stroke patients. We compared cMRI with TTE in the evaluation of Left Atrial (LA) size and pump function in a cohort of 44 patients with ischemic stroke. MATERIALS AND METHODS: The biplane method was utilized to acquire LA diameters as well as area measurements in both TTE and cMRI. We calculated LA volume (LAV), LAV index (LAVI), LA Global Longitudinal Strain (GLS) and LA pump function. Results were compared using paired two sample for means t-test. Lin's concordance correlation coefficient (CCC) and Bland-Altman methods quantified the agreement of measurements obtained by TTE and cMRI. RESULTS: LAVI measurements by cMRI were significantly larger (34.97 v. 28.81; p = 0.001) than by TTE. The concordance correlation demonstrated only a weak agreement between LA size measured by cMRI and TTE (ρc = 0.397; p= 0.001, 95% CI 0.16 - 0.59), and the Bland-Altman plot demonstrated that LAVI measured by cMRI averaged 6.3 ml/m2 larger magnitude than those obtained by TTE. CONCLUSIONS: Using TTE alone leads to an underestimation of LA abnormalities important in the evaluation of ischemic stroke patients. Nearly one in every five ischemic stroke patients evaluated based on the current guidelines may have a missed potential source of cardiac embolism.

Artificial intelligence in regional anaesthesia.

Ultrasound-guided regional anaesthesia is used to facilitate the real-time performance of the regional block, increase the block success and reduce the complication rate. Artificial intelligence (AI) has been studied in many medical disciplines with high success rates, especially radiology. The purpose of this article was to review the evolution of AI in regional anaesthesia. The role of AI is to identify and optimise the sonography image, display the target, guide the practitioner to advance the needle tip to the intended target and inject the local anaesthetic. AI supports non-experts in training and clinical practice and experts in teaching ultrasound-guided regional anaesthesia.

Bitter taste receptors establish a stable binding affinity with the SARS-CoV-2-spike 1 protein akin to ACE2.

COVID-19 is caused by the highly contagious SARS-CoV-2 virus, which originated in Wuhan, China, resulting in the highest worldwide mortality rate. Gustatory dysfunction is common among individuals infected with the Wild-type Wuhan strain. However, there are no reported cases of gustatory dysfunction among patients infected with the mutant delta variant. The reason behind this remains elusive to date. This in-silico-based study aims to unravel this clinical factor by evaluating the overall binding affinity of predominant bitter taste receptors associated with gustatory function (T2R-4, 10, 14, 19, 31, 38, 43, and 46) with the Receptor Binding Domain (RBD) of spike 1 (S1) protein of Wuhan (Wild)/delta-SARS-CoV-2 (mut1-T478K; mut2-E484K) variants. Based on docking and MM/PBSA free binding energy scores, the Wild RBD showed a stronger interaction with T2R-46 compared to the ACE2 protein. However, both delta variant mutants (mut1 and mut2) could not establish a stronger binding affinity with bitter taste receptor proteins, except for T2R-43 against mut1. In conclusion, the delta variants could not establish a better binding affinity with bitter taste receptors, contradicting the Wild variant that determines the severity of gustatory dysfunction among patients exposed to the delta and Wild SARS-CoV-2 variants. The study's inference also proposes T2R-46 as an alternate binding receptor target for RBD-S1 of Wild SARS-CoV-2, augmenting its virulence in all functional organs with compromised α-gustducin interaction and bitter sensitization. This in-silico-based study needs further wet-lab-based validation for a better understanding of the role of T2R-46-based viral entry in the human host.Communicated by Ramaswamy H. Sarma.

Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases.

The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance among these disorders. Relying on antibodies that have not been assessed for their ability to detect the diverse forms of aSyn may lead to inaccurate estimations of aSyn pathology in human brains or disease models. To address this challenge, we developed and characterized an expanded antibody panel that targets different sequences and post-translational modifications along the length of aSyn, and that recognizes all monomeric, oligomeric, and fibrillar aSyn conformations. Next, we profiled aSyn pathology across sporadic and familial Lewy body diseases (LBDs) and reveal heterogeneous forms of aSyn pathology, rich in Serine 129 phosphorylation, Tyrosine 39 nitration and N- and C-terminal tyrosine phosphorylations, scattered both to neurons and glia. In addition, we show that aSyn can become hyperphosphorylated during processes of aggregation and inclusion maturation in neuronal and animal models of aSyn seeding and spreading. The validation pipeline we describe for these antibodies paves the way for systematic investigations into aSyn pathological diversity in the human brain, peripheral tissues, as well as in cellular and animal models of synucleinopathies.

Assessment of brush biopsy findings and salivary LDH levels in oral mucosal lesions of tobacco users.

Introduction: The oral brush cytology is an alternative method developed to improve the efficacy of conventional cytology in oral potentially malignant disorder (OPMD), and salivary lactate dehydrogenase (LDH) which is a cytoplasmic enzyme has been widely used as a marker for diagnosing various diseases. The purpose of the study is to evaluate the brush biopsy findings and salivary LDH levels for the early diagnosis of premalignant and malignant lesions of the oral cavity. Materials and Methods: Patients with deleterious habits including tobacco-related lesions such as leukoplakia, tobacco pouch keratosis, and oral cancer were included in the study. For each patient, saliva sample was collected, brush biopsy was done and smears were prepared. Collected saliva samples were analysed for salivary LDH levels and prepared smears were analysed for dysplastic changes and statistical analysis was performed. Results: Out of 80 samples, 30 were leukoplakia, 45 were tobacco pouch keratosis and 5 were oral cancer, and 13 samples showed positive dysplastic changes, 26 samples showed atypical dysplastic changes and 41 samples showed no signs of dysplastic changes and concluded as negative. On comparing the results of brush biopsy findings and salivary LDH levels, the mean salivary LDH value for positive dysplasia was elevated and the P value was statistically significant (P value: 0.00). Conclusion: Brush biopsy showed good potential in detecting premalignant lesions and salivary LDH levels showed a marked increase which can be used as a diagnostic biomarker and serve as a potent diagnostic aid for early detection of malignancy.

Examining the Triple Burden of Malnutrition: Insights from a Community-Based Comprehensive Nutrition Survey among Indigenous Tribal Children (0-19 Years) in the Western Ghats Hills of India.

This article presents findings from a community-based cross-sectional study conducted in Attappadi, Kerala, India, aimed at assessing the prevalence of the triple burden of malnutrition among indigenous children aged 0-19 years. Historically, the indigenous population in Attappadi has faced significant developmental challenges, including high rates of malnutrition, infant mortality, and neonatal mortality. This study revealed alarming rates of undernutrition among children aged 0-59 months, with 40.9% experiencing stunting, 27.4% wasting, and 48.3% being underweight. Adolescent girls also suffered from undernutrition, with 21% classified as underweight and 43.3% experiencing stunting. Surprisingly, overweight or obesity was identified as a nutritional problem, affecting 1.4% of children aged 0-59 months, 4.2% of children aged 5-9 years, and 10.5% of adolescent girls. Additionally, a distressing proportion of young children aged 12-59 months (91.2%) were anaemic, with 50% diagnosed specifically with iron deficiency anaemia (IDA). Nearly all adolescent girls (96.6%) were reportedly suffering from anaemia. Deficiencies in vitamin B12, vitamin D, folate, and vitamin-A were prevalent among 35%, 20%, 16%, and 12% of children aged 12-59 months, respectively. The study underscores the urgent need for comprehensive interventions to address this triple burden of malnutrition. Recommendations include promoting culturally appropriate local food-based solutions, establishing participatory and community-led systems for health and nutrition information dissemination, and strengthening the nutrition surveillance system through village-level health and nutrition workers. By adopting a holistic approach, these interventions can help improve the nutritional status and well-being of the indigenous tribal children in Attappadi.

Mitigation of pesticide residue levels in the exposed dermal regions of occupationally exposed farmworkers by use of personal protective equipment.

Unsafe pesticide handling practices with the limited use of personal protective equipment (PPE) by the Indian farming groups lead to an increased risk of exposure to pesticides. Therefore, a community-based follow-up study based on dosimeters, wipes, and hand-wash technique was carried out to evaluate the dermal exposure to pesticides and to analyze the impact of the usage of PPE on minimizing the exposure among the farmworkers of Rangareddy district, Telangana, India. Risk in terms of hazard quotient (HQ), hazard index (HI), and safety analysis as margins of safety was assessed. Farmworkers averaged 18 years of farming experience and showed resistance to adopting good agricultural practices. Ten pesticide residues were detected in concentrations ranging from 0.000 to 246 mg ml-1 in hand-wash, 0.000 to 198.33 ng cm-2 in patch dosimeter, and 0.000 to 1,740 ng cm-2 in wipe samples collected from farmworkers not using PPE. The second phase includes the intervention study results that revealed a significant reduction both in the concentrations and the number of pesticide residues detected in the hand-wash, patch, and wipe samples of the farmworkers who have used the PPE provided to them (p < 0.01). Furthermore, the probabilistic health risk assessment in terms of the HQ values ranged from 0.02 to 1029.82, and HI was >1, suggesting the non-carcinogenic risks associated with dermal exposure to pesticides among them. Additionally, the safety risk assessment in terms of the margin of safety suggests that they follow risky handling practices. The study confirms that farmworkers are exposed to pesticides and emphasizes the significance of using PPE in reducing the risk.

Novel homozygous leptin receptor mutation in an infant with monogenic obesity.

Monogenic obesity can be caused by a mutation in one of the single genes involved in hunger and satiety. The most common mutations affect melanocortin 4 (MC4) followed by the leptin gene and its receptor. Leptin receptor (LEPR) gene mutation is an extremely rare endocrine disease characterized by early-onset obesity, hyperphagia in addition to pituitary hormone deficiency, and metabolic abnormalities. We report the case of a 12-month-old male infant born of a non-consanguineous marriage. He presented to us with rapid weight gain from 2 months of age along with hyperphagia. Biochemistry revealed a deranged lipid profile, elevated transaminases, and markedly raised serum leptin levels. On genetic analysis, a novel mutation was detected, which was a homozygous variation In exon 12 of the LEPR gene (chr1:g.65608901G>A) that resulted in the synonymous amino acid change of lysine at codon 584 proximal to donor splice site (p.Lys584). The in silico prediction of the variant was 'damaging' by MutationTaster2. The mutation was classified as a 'variant of uncertain significance' due to a lack of published literature and had to be correlated carefully with the clinical symptoms. It was recommended to do Sanger sequencing of the parents and other family members. However, due to financial constraints, the family could not afford the same. At the time of writing, funds were being arranged for procuring setmelanotide, which is a novel and effective therapy for monogenic obesity due to LepR mutation.

Residual Dialkyl Phosphate Metabolite Concentrations of Organophosphate Pesticides Among Indian Farmworkers: Implication of Exposure and Hazard Assessment.

OBJECTIVE: Biomonitoring of urinary dialkyl phosphate (DAP) metabolites, a sensitive biomarker to assess pesticides exposure and also to study the impact of the use of personal protective equipment (PPE). METHODS: A preintervention-postintervention study to biomonitor dimethylphosphate, diethylphosphate, diethylthiophosphate, and diethyl-dithiophosphate using liquid chromatography with tandem mass spectrometry among Indian farmworkers (n = 120). RESULTS: Dimethylphosphate was detected in all samples at a mean concentration of 74.91 µg · L -1 (17.616 µg · g -1 creatinine), whereas diethylthiophosphate and diethyl-dithiophosphate were detected in 88% and 82% of samples, respectively, among farmworkers who adopted unsafe pesticide-handling practices. Intervention studies showed a significant reduction in the urinary DAP metabolites detected among the farmworkers using PPE provided to them ( P < 0.01). CONCLUSIONS: Study confirms the exposure to pesticides among farmworkers and highlights the importance of the use of PPE to minimize exposure.

Assessment of sclerostin levels in the gingival crevicular fluid of patients with periodontitis: A clinico-biochemical crosssectional study.

Background: Sclerostin, a glycoprotein, plays a key role in regulating bone mass. In this study, sclerostin levels in the gingival crevicular fluid (GCF) were assessed in patients with Stage III Grade C generalized periodontitis (SIII-GC) and Stage III Grade B generalized periodontitis (SIII-GB). Methods: This cross-sectional study included 30 participants divided equally into three groups: group I (gingival health), group II (SIII-GC), and group III (SIII-GB). Clinical periodontal parameters like plaque index (PI), gingival bleeding index (GBI), probing pocket depth (PD), and clinical attachment level (CAL) were recorded. A sandwich ELISA was used to determine the sclerostin levels in GCF samples. One-way ANOVA and post hoc Tukey tests were used to analyze the clinical parameters and GCF sclerostin levels. The association between GCF sclerostin levels and periodontal parameters was assessed using Pearson's correlation coefficient (r). Results: Patients in groups II and III had much higher sclerostin levels in their GCF than in group I (P≤0.05). In contrast, no significant difference in sclerostin levels was observed between the two diseased conditions (P=0.841). Concerning periodontal parameters, a statistically significant difference was observed between the three groups. There was a positive correlation between the periodontal clinical parameters and the expression levels of sclerostin in GCF (P≤0.05). Conclusion: Increased expression of sclerostin in GCF in patients with periodontitis indicated that it could be considered a reliable biomarker of periodontal disease activity.

Artificial intelligence-coupled plasmonic infrared sensor for detection of structural protein biomarkers in neurodegenerative diseases.

Diagnosis of neurodegenerative disorders (NDDs) including Parkinson's disease and Alzheimer's disease is challenging owing to the lack of tools to detect preclinical biomarkers. The misfolding of proteins into oligomeric and fibrillar aggregates plays an important role in the development and progression of NDDs, thus underscoring the need for structural biomarker-based diagnostics. We developed an immunoassay-coupled nanoplasmonic infrared metasurface sensor that detects proteins linked to NDDs, such as alpha-synuclein, with specificity and differentiates the distinct structural species using their unique absorption signatures. We augmented the sensor with an artificial neural network enabling unprecedented quantitative prediction of oligomeric and fibrillar protein aggregates in their mixture. The microfluidic integrated sensor can retrieve time-resolved absorbance fingerprints in the presence of a complex biomatrix and is capable of multiplexing for the simultaneous monitoring of multiple pathology-associated biomarkers. Thus, our sensor is a promising candidate for the clinical diagnosis of NDDs, disease monitoring, and evaluation of novel therapies.

Surgical Episodes of Care for Price Transparency Using the Episode Grouper for Medicare.

OBJECTIVE: To explore the use of an episode grouper to more accurately identify the complete set of surgical services typically provided in a surgical episode of care and the corresponding range of prices, using colectomy for cancer as the example. BACKGROUND: Price transparency is an important policy issue that will require surgeons to better understand the components and cost of care. METHODS: This study uses the Episode Grouper for Medicare business logic to construct colectomy surgical episodes of care for cancer using Medicare claims data for the Boston Hospital Referral Region from 2012 to 2015. Descriptive statistics show the mean reimbursement based on patient severity and stage of surgery, along with the number of unique clinicians billing for care and the mix of services provided. RESULTS: The Episode Grouper for Medicare episode grouper identified 3182 colectomies in Boston between 2012 and 2015, with 1607 done for cancer. The mean Medicare allowed amount per case is $29,954 and varies from $26,605 to $36,850 as you move from low to high-severity cases. The intrafacility stage is the most expensive ($23,175 on average) compared with the pre ($780) and post ($6,479) facility stages. There is tremendous heterogeneity in the service mix. CONCLUSIONS: Episode groupers are a potentially valuable tool for identifying variations in service mix and teaming patterns that correlate with a total price. By looking at patient care holistically, stakeholders can identify opportunities for price transparency and care redesign that have heretofore been hidden.

Seeding the aggregation of TDP-43 requires post-fibrillization proteolytic cleavage.

Despite the strong evidence linking the transactive response DNA-binding protein 43 (TDP-43) aggregation to the pathogenesis of frontotemporal lobar degeneration with TDP-43, amyotrophic lateral sclerosis and several neurodegenerative diseases, our knowledge of the sequence and structural determinants of its aggregation and neurotoxicity remains incomplete. Herein, we present a new method for producing recombinant full-length TDP-43 filaments that exhibit sequence and morphological features similar to those of brain-derived TDP-43 filaments. We show that TDP-43 filaments contain a ß-sheet-rich helical amyloid core that is fully buried by the flanking structured domains of the protein. We demonstrate that the proteolytic cleavage of TDP-43 filaments and exposure of this amyloid core are necessary for propagating TDP-43 pathology and enhancing the seeding of brain-derived TDP-43 aggregates. Only TDP-43 filaments with exposed amyloid core efficiently seeded the aggregation of endogenous TDP-43 in cells. These findings suggest that inhibiting the enzymes mediating cleavage of TDP-43 aggregates represents a viable disease-modifying strategy to slow the progression of amyotrophic lateral sclerosis and other TDP-43 proteinopathies.

The immunotherapy advancement targeting malignant blastomas in early childhood.

Malignant blastomas develop relentlessly in all functional body organs inflicting severe health ailments in younger children. Malignant blastomas exhibit diverse clinical characteristics in compliance with their emergence in functional body organs. Surprisingly, neither of these preferred treatment types (surgery, radiotherapy, and chemotherapy) showed promise or were effective in treating malignant blastomas among child patients. N ew, innovative immunotherapeutic procedures including monoclonal antibodies and chimeric-antigen based receptor (CAR) cell therapy, coupled with the clinical study of reliable therapeutic targets and immune regulatory pathways targeting malignant blastomas, have attracted the attention of clinicians recently.

Longitudinal impact of stressful life events on HIV-related risk and psychosocial problems among MSM in Chennai and Mumbai, India.

BACKGROUND: Studies show that stressful life events (SLE) (e.g., discrimination, financial problems) can lead to psychosocial problems and exacerbate condomless anal sex (CAS) without protection via pre-exposure prophylaxis (PrEP) among men who have sex with men. However, few studies have examined this relationship among men who have sex with men in India, and none have examined this longitudinally. METHODS: As a part of an HIV-prevention intervention, 608 MSM from Chennai and Mumbai, India, completed behavioral surveys at baseline, 4, 8, and 12 months. We used longitudinal generalized estimating equations (GEE) modeling to examine the relationship between SLE and its severity and subsequent psychosocial problems, CAS, and history of diagnosed sexually transmitted infection (STI). All models are adjusted for age, sexual identity, intervention arm, human immunodeficiency virus status, and recruitment city. RESULTS: The number of SLE and their corresponding perceived impact score remained consistent at each time point. In multivariable GEE models, the number of SLE was predictive of CAS, depression, and harmful drinking. Similarly, the ratio of the impact of SLE was predictive of CAS, depression, and diagnosed STI. However, harmful drinking was not predictive in this model. CONCLUSIONS: These findings provide evidence that can inform future interventions, which can be used to enhance self-acceptance, coping skills, and other forms of resiliency.

To Vaccinate or Not to Vaccinate-Reasons of Willingness and Reluctance of Students against SARS-CoV-2 Vaccination-An International Experience.

Despite the vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) being reported to be safe and effective, the unwillingness to vaccinate and doubts are still common. The aim of this international study was to assess the major reasons for the unwillingness to vaccinate in a group of students from Poland (n = 1202), Bangladesh (n = 1586), India (n = 484), Mexico (n = 234), Egypt (n = 566), Philippines (n = 2076), Pakistan (n = 506), Vietnam (n = 98) and China (n = 503). We conducted an online cross-sectional study that aimed to assess (1) the percentage of vaccinated and unvaccinated students and (2) the reasons associated with willingness/unwillingness to the vaccine. The study included 7255 respondents from 9 countries with a mean age of 21.85 ± 3.66 years. Only 22.11% (n = 1604) of students were vaccinated. However, the majority (69.25%, n = 5025) expressed a willingness to be vaccinated. More willing to vaccinate were students in informal relationships who worked mentally, used psychological/psychiatric services before the pandemic, and studied medicine. There are cultural differences regarding the reasons associated with the unwillingness to vaccinate, but some 'universal' might be distinguished that apply to the whole group.