Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity.

For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.

Introducing a novel histopathological scoring system to assess disease activity and chronicity in cutaneous lichen planus: A proposal.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory disorder caused by an autoimmune attack by cytotoxic T-cells. The clinical course is variable, with episodes of remission and exacerbation. A clinicopathological scoring system for cutaneous LP is not available for effectively assessing disease severity and monitoring treatment response. This study was designed with the aim of proposing an objective and reproducible scoring system, comprising histopathological features of active and chronic disease, and to correlate these scores with clinical morphology groups. METHODOLOGY: This is a retrospective study of 200 cases of cutaneous LP, which were categorized into five clinical groups (I-V) at the time of biopsy. The corresponding histopathological feature was assigned a score based on feature of active and chronic disease. Individual scores were summated to calculate a histopathological index (index [AI] and chronicity index [CI]). The comparison of indices between various clinical groups was performed by Mann-Whitney U test. RESULTS: The median AI was lowest (1) for post-inflammatory hyperpigmentation (clinical group I) and highest (7) for the bullous group (clinical group IV). The median CI (7) was highest for the scarring group (clinical group V). The difference between median AI of clinical group I (post-inflammatory hyperpigmentation) and rest of the groups (clinical groups II, III, IV, and V) was statistically significant (p value <0.05). CONCLUSION: We present this clinico-histopathological scoring system as a reliable and facile method of assessing the activity and severity of LP.

Efficacy of polyherbal formulations for prevention of COVID-19 infection in high-risk subjects: A randomized open-label controlled clinical trial.

COVID-19 is arguably the biggest health crisis the world has faced in the 21st century. Therefore, two of the polyherbal formulations, Infuza and Kulzam were assessed for the prevention of COVID-19 infection as a repurposed medication. Four hundred seven high-risk subjects were recruited in the present open-label randomized controlled clinical trial for eligibility. After assessment for eligibility, remaining 251 subjects were randomized to the test and control groups. Further, 52 high-risk subjects in Infuza, 51 in Kulzam, 51 in Infuza & Kulzam and 53 in control group completed the 14 days of intervention/assessment. The phenotyping of lymphocytes at baseline (0 day) and after 14 days of treatment was carried out by flow cytometry assays. A total of 15.09% high-risk subjects in control group turned positive as compared to only 7.69% in Infuza, 3.92% in Kulzam and 1.96% in Infuza & Kulzam groups. The rate of conversion to COVID-19 infection in Infuza & Kulzam group was minimal and statistically significant as compared to control group (p0.017). No significant changes in phenotype of lymphocytes (T, B, NK cells), absolute lymphocyte count and cytokine levels were found in study groups. However, there was a decreasing trend of hs-CRP level in high-risk subjects after intervention of polyherbal formulations for 14 days. The combination of Infuza and Kulzam may synergistically prevent COVID-19 infection in high-risk subjects of COVID-19.

Autologous Calvarial Bone Remodeling Technique for Small to Medium-Sized Cranial Defects in Young Children: The "Switch-Cranioplasty" Technique.

INTRODUCTION: Reconstruction of cranial defects in children less than 2 years of age, particularly when there is an associated dural defect, is challenging due to the need to accommodate active skull growth, limited options for autologous bone graft and thin calvarial bones. We use a simple remodeling technique that exploits the normal dura's inherent potential for new bone growth while covering the dural defect with adjacent skull. CASE PRESENTATION: We describe an alternating, two-piece craniotomy or "switch-cranioplasty technique" to repair an occipital meningocele. The two pieces of craniotomy bone flap created around the existing skull and dural defect are switched in the horizontal plane in order to cover the site of the defect and the abnormal dura of the meningocele closure. The area of the original skull defect is transposed laterally over the normal dura. The healing of the lateral skull defects is facilitated with autologous bone chips and dust and covered by periosteal flaps that stimulate spontaneous re-ossification. DISCUSSION: The advantages of this technique are the use of autologous bone adjacent to the skull defect, incorporation of the autologous bone into the growing skull, an acceptable cosmetic and functional outcome in a simple manner. The indications can be extended to include small to medium-sized calvarial defects secondary to leptomeningeal cyst and trauma.

Mathematical model of Ebola and Covid-19 with fractional differential operators: Non-Markovian process and class for virus pathogen in the environment.

Differential operators based on convolution definitions have been recognized as powerful mathematics tools to help model real world problems due to the properties associated to their different kernels. In particular the power law kernel helps include into mathematical formulation the effect of long range, while the exponential decay helps with fading memory, also with Poisson distribution properties that lead to a transitive behavior from Gaussian to non-Gaussian phases respectively, however, with steady state in time and finally the generalized Mittag-Leffler helps with many features including the queen properties, transitive behaviors, random walk for earlier time and power law for later time. Very recently both Ebola and Covid-19 have been a great worry around the globe, thus scholars have focused their energies in modeling the behavior of such fatal diseases. In this paper, we used new trend of fractional differential and integral operators to model the spread of Ebola and Covid-19.

What's known about implementing co-located paediatric integrated care: a scoping review.

Several studies have demonstrated clinical benefits of integrated care for a range of child and adolescent mental health outcomes. However, there is a significant gap between the evidence for efficacy of integrated care interventions vs their implementation in practice. While several studies have examined large-scale implementation of co-located integrated care for adults, much less is known for children. The goal of this scoping review was to understand how co-located mental health interventions targeting children and adolescents have been implemented and sustained. The literature was systematically searched for interventions targeting child and adolescent mental health that involved a mental health specialist co-located in a primary care setting. Studies reporting on the following implementation outcomes were included: acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability. This search identified 34 unique studies, including randomized controlled trials, observational studies, and survey/mixed method approaches. Components facilitating implementation of on-site integrated behavioural healthcare included interprofessional communication and collaboration at all stages of implementation; clear protocols to facilitate intervention delivery; and co-employment of integrated care providers by specialty clinics. Some studies found differences in service use by demographic factors, and others reported funding challenges affecting sustainability, warranting further study.

Atlantoaxial instability associated with pan cervical vertebral fusion: Report on management of 4 cases.

We report a series of four patients aged 4, 5, 14, and 27 years (1 male and 3 female patients) with severe shortening of the neck and torticollis since early childhood who presented with complaint of pain in the nape of neck as the primary symptom. All four patients had relatively well preserved neurological functions. One patient had vertical mobile and reducible atlantoaxial dislocation, and 3 patients had anteroposterior mobile and reducible dislocation. There was assimilation of atlas in 1 patient. The arch of atlas was bifid in 3 patients. Two patients underwent atlantoaxial fixation. Both the patients were relieved of neck pain after their surgery. The potential surgical difficulties due to the presence of severe shortening of neck height and marginal presenting symptoms favored conservative observation in the other 2 patients. Follow-up ranged from 6 to 84 months. All patients are functionally and socially active.

Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial.

BACKGROUND: Nutritional modulation remains central to the management of metabolic syndrome. Intervention with cinnamon in individuals with metabolic syndrome remains sparsely researched. METHODS: We investigated the effect of oral cinnamon consumption on body composition and metabolic parameters of Asian Indians with metabolic syndrome. In this 16-week double blind randomized control trial, 116 individuals with metabolic syndrome were randomized to two dietary intervention groups, cinnamon [6 capsules (3 g) daily] or wheat flour [6 capsules (2.5 g) daily]. Body composition, blood pressure and metabolic parameters were assessed. RESULTS: Significantly greater decrease [difference between means, (95% CI)] in fasting blood glucose (mmol/L) [0.3 (0.2, 0.5) p = 0.001], glycosylated haemoglobin (mmol/mol) [2.6 (0.4, 4.9) p = 0.023], waist circumference (cm) [4.8 (1.9, 7.7) p = 0.002] and body mass index (kg/m2 ) [1.3 (0.9, 1.5) p = 0.001] was observed in the cinnamon group compared to placebo group. Other parameters which showed significantly greater improvement were: waist-hip ratio, blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, and high-density lipoprotein cholesterol. Prevalence of defined metabolic syndrome was significantly reduced in the intervention group (34.5%) vs. the placebo group (5.2%). CONCLUSION: A single supplement intervention with 3 g cinnamon for 16 weeks resulted in significant improvements in all components of metabolic syndrome in a sample of Asian Indians in north India. TRIAL REGISTRATION: The clinical trial was retrospectively registered (after the recruitment of the participants) in ClinicalTrial.gov under the identification number: NCT02455778 on 25th May 2015.

Hypoxic Stress Induced TREM-1 and Inflammatory Chemokines in Human Peripheral Blood Mononuclear Cells.

Hypoxia is a condition of low pO2, which creates a unique microenvironment affecting cell phenotype and subsequent immune response generation. Little is known about the impact of hypoxia on the phenotypic expression of NK cell, TREM-1, TLR-4 and inflammatory chemokines. In the present study we have determined the frequency of peripheral blood populations of CD16/CD56 (NK Cells) expressing cells, presence of activation marker CD354 (TREM-1), Toll like receptor (CD 284) on the cell surface and chemokines IL-8 and RANTES in the cellular supernatant of normoxia and hypoxia exposed cells by flow cytometry. GRP-78 expression was determined by reverse transcriptase polymerase chain reaction. The blood was collected from healthy individuals and exposed to normoxic and hypoxic (0.5 %) environment for 24 h. The percentage of NK cells (CD 16/56) was marginally up regulated while TLR-4 expression was diminished in hypoxia exposed cells as compare to the normoxic cells. TREM-1 expression was significantly up-regulated (p < 0.05) in hypoxia as compared to the normoxic control. In addition when monocytic cell line THP-1 was exposed to 0.5 % hypoxia for 24 h, TLR4 expression was significantly decreased in hypoxic cells as compared to normoxic cells. Furthermore, GRP-78 mRNA expression was also upregulated by hypoxia or LPS exposure. These events are paralleled by strengthening up-regulation of the chemokines IL-8 and RANTES an otherwise necessary event for the chemotaxis of the neutrophils and macrophages to the inflammatory site. In conclusion, this study provides a novel insight into the mechanism linking low oxygen tension to the regulation of immune and inflammatory responses, leading to new perspectives of the role of hypoxia in programming immune cell functions.

Improved diabetic retinopathy severity classification using squeeze-and-excitation and sparse light weight multi-level attention u-net with transfer learning from xception.

AIMS: Diabetic Retinopathy (DR) is a significant cause of vision loss in diabetic patients, making early detection and accurate severity classification essential for effective management and prevention. This study aims to develop an enhanced DR severity classification approach using advanced model architectures and transfer learning to improve diagnostic accuracy and support better patient care. METHODS: We propose a novel model, Xception Squeeze-and-Excitation Sparse Lightweight Multi-Level Attention U-Net (XceSE_SparseLwMLA-UNet), designed to classify DR severity using fundus images from the Messidor 1 and Messidor 2 datasets. The XceSE_SparseLwMLA-UNet integrates several advanced mechanisms: the Squeeze-and-Excitation (SE) mechanism for adaptive feature recalibration, the Sparse Lightweight Multi-Level Attention (SparseLwMLA) mechanism for effective contextual information integration, and transfer learning from the Xception architecture to enhance feature extraction capabilities. The SE mechanism refines channel-wise feature responses, while SparseLwMLA enhances the model's ability to identify complex DR patterns. Transfer learning utilizes pre-trained weights from Xception to improve generalization across DR severity levels. RESULTS: The proposed XceSE_SparseLwMLA-UNet model demonstrates superior performance in DR severity classification, achieving higher accuracy and improved multi-class F1 scores compared to existing models. The model's color-coded segmentation outputs offer interpretable visual representations, aiding medical professionals in assessing DR severity levels. CONCLUSIONS: The XceSE_SparseLwMLA-UNet model shows promise for advancing early DR diagnosis and management by enhancing classification accuracy and providing valuable visual insights. Its integration of advanced architectural features and transfer learning contributes to better patient care and improved visual health outcomes.

Innovative COVID-19 Point-of-Care Diagnostics Suitable for Tuberculosis Diagnosis: A Scoping Review.

Introduction: Rapid and accurate point-of-care (POC) tuberculosis (TB) diagnostics are a key priority to close the TB diagnostic gap of 3.1 million people without a diagnosis. Leveraging the recent surge in COVID-19 diagnostic innovation, we explored the potential adaptation of commercially available SARS-CoV-2 tests for TB diagnosis, aligning with World Health Organization (WHO) target product profiles (TPPs). Methods: A scoping review was conducted following PRISMA-ScR guidelines to systematically map commercially available POC molecular and antigen SARS-CoV-2 diagnostic tests potentially meeting the TPPs for TB diagnostic tests for peripheral settings. Data were gathered from PubMed/MEDLINE, bioRxiv, and medRxiv, along with publicly accessible in vitro diagnostic test databases, and developer websites, up to November 23, 2022. Data on developer and test attributes, operational characteristics, pricing, and clinical performance were charted using standardized data extraction forms. Each identified test was evaluated using a standardized scorecard. A narrative synthesis of the charted data is presented. Results: Our database search yielded 2,003 studies, from which 408 were considered eligible. Among these, we identified 58 commercialized diagnostic devices, including 17 near-POC antigen tests, one POC molecular test, 29 near-POC molecular tests, and 11 low-complexity molecular tests. We summarized the detailed characteristics, regulatory status, and clinical performance data of these tests. The LumiraDx (Roche, Switzerland) emerged as the highest- scoring near-POC antigen platform, while Visby (Visby, USA) was the highest-performing near-POC molecular platform. The Lucira Check-It (Pfizer, USA) was noted as the sole POC molecular test. The Idylla TM (Biocartis, Switzerland) was identified as the leading low- complexity molecular test. Discussion: We highlight a diverse landscape of commercially available diagnostic tests suitable for potential adaptation to TB POC testing. This work aims to bolster global TB initiatives by fostering stakeholder collaboration, leveraging COVID-19 diagnostic technologies for TB diagnosis, and uncovering new commercial avenues to tackle longstanding challenges in TB diagnosis.

Trajectories and correlates of mental health among urban, school-age children during the COVID-19 pandemic: a longitudinal study.

BACKGROUND: The COVID-19 pandemic posed numerous obstacles to psychosocial wellbeing for children. We conducted a longitudinal study to evaluate child mental health and social risks during the pandemic. METHODS: Participants were 172 caregivers of children aged 6-11 years old who attended well child visits within 6 months before pandemic onset at an urban safety net hospital in the US. Prepandemic data was extracted from the electronic medical record, and surveys were administered at three time points between August 2020 and July 2021. We measured mental health symptoms with the Pediatric Symptom Checklist-17, social risks (e.g., food and housing insecurity) with the THRIVE questionnaire, and school modality (in-person, hybrid, remote). RESULTS: Compared to pre-pandemic, children had significantly higher PSC-17 total scores (overall mental health symptoms) and THRIVE total scores (total burden of social risks) at all three mid-pandemic waves. Using longitudinal mixed models accounting for time, social risks, and school modality, both social risks (B = 0.37, SE = 0.14, p < 0.01) and school modality were significantly associated with PSC-17 scores (B = - 1.95, SE = 0.63, p < 0.01). Children attending in-person school had fewer mental health symptoms than those attending remote or hybrid school. CONCLUSION: Mental health symptoms and social risks remained significantly higher fifteen months after the onset of the COVID-19 pandemic compared to prepandemic. In-person attendance at school appeared protective against persistently elevated mental health symptoms.

Martian atmospheric hydrogen and deuterium: Seasonal changes and paradigm for escape to space.

Mars' water history is fundamental to understanding Earth-like planet evolution. Water escapes to space as atoms, and hydrogen atoms escape faster than deuterium giving an increase in the residual D/H ratio. The present ratio reflects the total water Mars has lost. Observations with the Mars Atmosphere and Volatile Evolution (MAVEN) and Hubble Space Telescope (HST) spacecraft provide atomic densities and escape rates for H and D. Large increases near perihelion observed each martian year are consistent with a strong upwelling of water vapor. Short-term changes require processes in addition to thermal escape, likely from atmospheric dynamics and superthermal atoms. Including escape from hot atoms, both H and D escape rapidly, and the escape fluxes are limited by resupply from the lower atmosphere. In this paradigm for the escape of water, the D/H ratio of the escaping atoms and the enhancement in water are determined by upwelling water vapor and atmospheric dynamics rather than by the specific details of atomic escape.

Investigating the morphology and genetics of scalp and facial hair characteristics for phenotype prediction.

Microscopic traits and ultrastructure of hair such as cross-sectional shape, pigmentation, curvature, and internal structure help determine the level of variations between and across human populations. Apart from cosmetics and anthropological applications, such as determining species, somatic origin (body area), and biogeographic ancestry, the evidential value of hair has increased with rapid progression in the area of forensic DNA phenotyping (FDP). Individuals differ in the features of their scalp hair (greying, shape, colour, balding, thickness, and density) and facial hair (eyebrow thickness, monobrow, and beard thickness) features. Scalp and facial hair characteristics are genetically controlled and lead to visible inter-individual variations within and among populations of various ethnic origins. Hence, these characteristics can be exploited and made more inclusive in FDP, thereby leading to more comprehensive, accurate, and robust prediction models for forensic purposes. The present article focuses on understanding the genetics of scalp and facial hair characteristics with the goal to develop a more inclusive approach to better understand hair biology by integrating hair microscopy with genetics for genotype-phenotype correlation research.

Infections Associated Hemophagocytosis-Secondary HLH Mimics in Children!"

Infection-associated hemophagocytosis is a diagnostic challenge. The varied presentation makes timely diagnosis difficult. We report two cases with unusual presentation of well-established secondary triggers for hemophagocytic lymphohistiocytosis.

A Clinico-Histopathological Study of Lupus Vulgaris at a Tertiary Care Centre.

Background and objectives Lupus vulgaris is a chronic, progressive, paucibacillary form of cutaneous tuberculosis that occurs in persons with moderate to high immunity. Due to its varied clinical presentation, it can masquerade as different dermatological conditions. This study describes the demographic patterns and varieties of clinical manifestations that can be possible in this curable illness. Methods This study was conducted over two years and included 19 patients with histopathologically confirmed lupus vulgaris in Odisha, India. Demographic data, clinical features, and response to treatment are presented. Results Thirteen cases (68.4%) were seen in adults and six (31.6%) in pediatric patients. The lower limbs were the more affected (n=10), followed by the upper limb (6), the face (2), and the chest (1). All but one patient had plaque-type lesions. On histopathology, all showed a tuberculoid granuloma with no demonstration of acid-fast bacilli with Ziehl-Neelsen staining. Conclusion In the present study, the incidence was mostly observed in the young and higher activity age groups (5-40 years). Plaque-type lesions were most commonly encountered. In histopathology, all the cases had tubercular granuloma-type lesions without any incidence of malignant transformations. All the patients responded well to conventional multi-drug anti-tubercular chemotherapeutic regimens.

Sex-specific variations in global DNA methylation levels with age: a population-based exploratory study from North India.

Purpose: Aging is one of the most important risk factors for a number of human diseases. Epigenetic alterations, including changes in DNA methylation patterns, have been reported to be one of the hallmarks of aging. Being a malleable process, the role of site-specific DNA methylation in aging is being extensively investigated; however, much less attention has been given to alterations in global DNA methylation with aging at the population level. The present study aims to explore overall and sex-specific variations in global DNA methylation patterns with age. Methods: A total of 1,127 adult individuals (792 females) aged 30-75 years belonging to Haryana, North India, were recruited. Socio-demographic data was collected using a pretested interview schedule. Global DNA methylation analysis, of peripheral blood leucocyte (PBL) DNA, was performed using the ELISA-based colorimetric technique. Results: Though the overall correlation analysis revealed a weak inverse trend between global DNA methylation and age, the adjusted regression model showed no significant association between global DNA methylation and age. In age-stratified analysis, global DNA methylation levels were found to be fairly stable until 60 years of age, followed by a decline in the above-60 age group. Further, no significant difference in DNA patterns methylation pattern was observed between males and females. Conclusion: Overall, the study suggests a lack of association between global DNA methylation and age, especially until 60 years of age, and a similar DNA methylation pattern between males and females with respect to age.

A Cross-Sectional Assessment of Quantitative Epidermal Melanin and Erythema Indices among North Indians.

Background: Remarkable diversity of skin tones among Indians ranging from pale pinkish to dark brown appears to be an ideal choice for the assessment of skin pigment variation. Aim: The present study was designed to assess the variation observed in melanin and erythema indices among north Indians. Material and Methods: Skin reflectance data (n = 574) was collected from six diverse populations of north India using DermaSpectrometer (DSM II ColorMeter) followed by statistical analysis to investigate the impact of geographical location and gender on constitutive skin pigmentation. Results: The melanin index (MI) varied between 17.93 and 56.92 (Mean (M) = 35.80 ± 6.26) whereas the erythema index (EI) varied between 4.92 and 18.82 (M = 10.48 ± 2.68). MI and EI of females were found to be significantly lower than males (P < 0.001). Geographical location exhibited a significant association with MI and EI (P < 0.001). Furthermore, we have noted a positive correlation between MI and EI (P < 0.001). Conclusion: The study has refined our understanding of skin pigmentation variation among north Indians in terms of significant association with geographical location {MI: F (5,568) = 31.07, P < 0.001; EI: F (5,568) = 73.37, P < 0.001} and gender {MI: t (386) = -4.06, P < 0.001; EI: t (386) = -11.96, P < 0.001} and rendered opportunities for further studies.

Antimicrobial Properties and Substantivity of Gentamicin, Amoxicillin and Metronidazole (GAM) Antibiotic Solution with Chitosan as a Root Canal Irrigant - A Preliminary Study.

Irrigation is one of the steps that is very crucial in a high-quality endodontic treatment. Hence, irrigant with good substantivity is essential which must not only be effective for the dissolution of the organic tissues but also effectively eliminate bacterial contamination. The aim of the study was to investigate and compare the antimicrobial efficacy of gentamicin, amoxicillin, and metronidazole (GAM) antibiotic solution, chitosan and their combination (GAMC), and analyze their sustained release property. Mueller-Hinton agar medium was inoculated with E. faecalis. The medicaments were then poured at the center of the plate in the prepared wells and incubated at 37°C. Antibacterial property of each medicament was evaluated by measuring the diameter of the zone of inhibition at the end of 48 hours. The substantivity of GAM antibiotic solution and the GAMC was checked using an ultraviolet spectrophotometer. The GAMC demonstrated the strongest antimicrobial activity and good sustained-release properties. Distilled water showed no activity, and chlorhexidine acted as the positive control. Conclusion: The combination of gentamicin, amoxicillin, and metronidazole (GAM) solution with chitosan (GAMC) can be used as an alternative intracanal irrigant as it was found to be a potent antibacterial agent.