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Background: Langerhans cell histiocytosis (LCH) has a variable presentation. Gastrointestinal involvement is rare and portends a poor prognosis in LCH. Case report: Herein, we describe the presentation, progression, management, and outcome of an 11-month-old female infant with LCH. The patient presented with severe acute malnutrition, hepatosplenomegaly, and gastrointestinal involvement in the form of persistent vomiting. She was managed with chemotherapy initially and subsequently developed complete duodenal narrowing. She underwent Kimura's duodenojejunostomy and improved. Hence, chemotherapy was restarted. Two months later, she developed features of intestinal obstruction with intraoperative findings of ileal gangrene requiring adhesiolysis, ileal resection, and ileostomy. Subsequently, she succumbed to sepsis. Conclusion: This case report aims to highlight the atypical gastrointestinal manifestations of LCH and the challenges faced in managing such a case.

Osteoarthritis (OA) is a chronic condition that can lead to pain, disability, and loss of function. There are currently few pharmacological treatments, and none are disease modifying. It is important to identify new treatments to reduce associated morbidity, as well as high costs to the individual and society. OA pathogenesis involves the cartilage, synovium, and bone, with many mediators in the immune system implicated in this process. These provide several targets for pharmacotherapy that can be divided into treatments that target pain or disease-modifying drugs that aim to maintain the joint. Previous OA trials conducted have failed to either meet efficacy or safety measures. Notably, anti-nerve growth factor drugs that were superior to placebo had several adverse events that subsequently limited their usage. The aim of this paper is to highlight the current treatments under investigation that are in Phase II and III of development. This review searched trials that have been registered on clinicaltrials.gov with the term “osteoarthritis” and a primary completion date of 2021 or after that are in Phase II and III. This identified 252 studies, 52 of which were included in the review after screening and eligibility checks, that were then categorised as either targeting pain and inflammatory pathways or disease-modifying osteoarthritis drugs. Two further papers were included as they present two distinct therapies for hand OA. The results showed numerous avenues in development, with promising results, and provides hope to reduce the global burden of morbidity. It is important that these treatments are affordable for this chronic condition.

With the advent of technology, it has become possible to perform direct numerical simulations and the demand for high accuracy computing is increasing. Numerical simulations play an important part in understanding physics of the flow and instability mechanism in flows. For high accuracy, numerical schemes must be chosen that satisfy the physical dispersion relation, should not amplify or attenuate the solution and resolve all possible length and time scales. In the present paper, spectral stability analysis of linear convection equation is performed using first order forward difference (FD1) method and fourth order Runge Kutta (RK4) method, consisting of four stages, for time discretization and a second order central difference (CD2) method for evaluating spatial derivative. The results show that the presence of numerical instability for FD1 method is independent of the CFL number, consistent with the stability analysis which showed FD1 method to be unconditionally unstable. However, for RK4 method, the solution is found to be neutrally stable only for a particular range of CFL number, even stable solution introduced error by attenuating the computed or analytical solution.

Mauriac syndrome (MS) is an exceptionally rare disorder occurring in poorly controlled Type-1 diabetic patients. The consequences include dwarfism, obesity, hepatomegaly, delayed puberty, growth failure and higher levels of transaminase enzyme. We report a case of an adolescent female with classical features of Mauriac syndrome.

Abstract Introduction There has been an advent in the use of Mobile Apps in the academic space. The pandemic hastened their usage, and forced us to rapidly innovate in order to meet the educational needs of our students. Also, Mobile Apps have been known to facilitate self-learning, make it enjoyable, and personalize the pace of learning of the individual. Given the level of skill-learning in Physiotherapy education, the use of Mobile Apps can pose a challenge, as well as offer an opportunity to explore its scope to enhance learning, and create innovative pedagogic strategies. There are a very few learning mobile apps that have been assessed in Physiotherapy education. Aim To develop, establish content validity and internal consistency of a curriculum based App on the kinesiology of normal Gait for bachelor of physiotherapy students, and to evaluate the App with regards to use, quality, engagement, and overall experience. Materials & methods In the first phase, a mobile app based on a bachelor of physiotherapy Gait curriculum was developed and validated using Delphi procedure, with 80% agreement criteria, by a group of experts. Subsequently, the App was rated by 200 users on: engagement, aesthetics, information, subjective quality. Results The content validity index following 2 rounds of Delphi was found to be 0.88. Also, therapists found the App easy to use, and 80% gave it a rating of > 3 stars. Conclusion Creating, designing, implementing, and evaluating the efficacy of a Gait App as a means to teaching the GAIT component to physiotherapy students was found to be appealing and beneficial.

Background: Alcohol use disorders (AUDs) are emerging as a substance use disorder having various psychological and physical ill effects leading to hampering of individual’s productivity and functioning. Aims: The aim of this study was to evaluate the efficacy of ketamine in enhancing confidence levels to abstain from alcohol. Methods: Eighteen patients were administered ketamine intravenously after detoxification; a total of three doses, with a 3-day gap between each. The Alcohol Abstinence Self-Efficacy Scale was used to measure their confidence in abstaining from alcohol. Results: The study revealed a significant increase in mean confidence scores after three ketamine sessions, with a final assessment showing a 51.98% increase in confidence from baseline. Conclusions: The study found that ketamine therapy significantly increased confidence levels in individuals with AUD to abstain from alcohol, with P = 0.05 threshold. However, the impact may wane over time, suggesting the need for additional support or maintenance treatments.

Introduction: Adenoids are a type of nasopharyngeal lymphoid tissue that is a component of Waldeyer’s ring. They are typically present from birth, reach their maximum size between the ages of 7 and 10 years, and then gradually decrease in size to become atrophied in adulthood. The objective of the current study is to compare conventional adenoidectomy using curette with power-assisted adenoidectomy. Materials and Methods: This randomized clinical trial was conducted at Teerthanker Mahaveer Medical College and Research Center from March 2023 to August 2023. A total of 40 patients were planned for adenoidectomy and randomly allocated under two groups. The conventional curettage adenoidectomy method was done on patients in Group A and patients in Group B who underwent power-assisted adenoidectomy using microdebrider. Both the groups were further compared in terms of surgical clearance of adenoids, operative time taken in procedure, injury to surrounding structures, and symptom score improvement on follow-up. Results: Surgical clearance was excellent in Group B with no adenoid tags left in all 20 (100%) patients, whereas few tags were left in 18 (90%) patients in Group A (P < 0.0001). The mean operative time (in minutes) for Group A was 22.4 ± 1.67, whereas Group B was 18.1 ± 1.76 (P = 0.001). Postoperative pain score in Group A was 3.7 ± 1.63, whereas for Group B was 2.8 ± 1.01 (P < 0.043). Recovery time in terms of number of days to return to normal diet and activities in Group A was 3.1 ± 0.3 days, whereas Group B was less 2.1 ± 0.2 days (P < 001). Postoperative nasal symptom score at 6 weeks in Group A was 1 in 1 patient and 2 in 4 patients with mean of 0.45 ± 83, whereas in Group B was 0 (P = 0.043). Conclusion: It was concluded from the study that power-assisted adenoidectomy was a better surgical procedure than conventional adenoidectomy. There was better improvement in nasal symptom score and surgical clearance by power-assisted adenoidectomy. Postoperative pain score and time taken for recovery after surgery were also less in power-assisted adenoidectomy.

Introduction: Labour analgesia practices have evolved significantly over the past years, with most of the current practices being evidence-based. Labour analgesia is considered a standard of care in resource-rich countries. However, in resource-limited countries such as India, there is a lack of awareness, and round the clock availability of labour analgesia services across the country. This raises significant challenges in establishing successful labour analgesia programs. Methods: This survey was conducted using multi-question Google Form@, so as to improve our understanding of labour analgesia practices in India. Our primary objective was to study the prevalence of labour analgesia practices amongst anaesthesiologists across India. Our secondary objectives included the work profile of anaesthesiologists providing labour analgesia, common techniques of labour analgesia practised, drugs used and common complications as well as side-effects encountered. Results: The results of our survey showed that 72.9% of the respondents practised labour analgesia in one form or the other. Practitioners in non-government facilities such as private hospitals, private medical colleges, and nursing homes accounted for more than 60% of the total labour analgesia delivered. Government medical colleges fared the best among practitioners at government-owned facilities. Approximately 85% of those polled agreed that the most common way of pain relief in a labouring patient was regional analgesia. The most prevalent was labour epidural (59.4%), followed by a single shot spinal analgesic, while 29% of anaesthesiologists used systemic analgesia. Conclusion: The impediments to delivering widespread labour analgesia services across India were poor infrastructure and high costs.

Abstract Identification of novel subgroups of type 2 diabetes (T2D) has helped improve its management. Most classification techniques focus on clustering or subphenotyping but not on both. This study aimed to compare both these methods and examine the rate of T2D remission in these subgroups in the Indian population. K-means clustering (using age at onset, HbA1C, BMI, HOMA2 IR and HOMA2%B) and subphenotyping (using homeostatic model assessment (HOMA) estimates) analysis was done on the baseline data of 281 patients with recently diagnosed T2D who participated in a 1-year online diabetes management program. Cluster analysis revealed three distinct clusters: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), and mild obesity-related diabetes (MOD) while subphenotyping showed four distinct categories: hyperinsulinemic, insulinopenic, classical, and nascent T2D. Comparison of the two approaches revealed that the clusters aligned with phenotypes based on shared characteristics of insulin sensitivity (IS) and beta cell function (BCF). Clustering correctly identified individuals in nascent group (high IS and BCF) as having mild obesity related diabetes which subphenotyping did not. Post-one-year intervention, higher remission rates were observed in the MOD cluster (p = 0.383) and the nascent phenotype showing high IS and BCF (p = 0.061, Chi-Square test). In conclusion, clustering based on a comprehensive set of parameters appears to be a superior method for classifying T2D compared with pathophysiological subphenotyping. Personalized interventions may be highly effective for newly diagnosed individuals with high IS and BCF and may result in higher remission rates in these individuals. Further large-scale studies are required to validate these findings.

Abstract A biotransformation pair consisting of vinblastine: vincristine present in the Catharanthus roseus plant is of immense pharmacological significance. In this study, we successfully transformed vinblastine into vincristine outside the plant using Pseudomonas aeruginosa 8485 and Pseudomonas fluorescens 2421 and evaluated the antiangiogenic potential of thus produced vincristine through the CAM assay. The toxicity assay showed that both Pseudomonas spp. can tolerate varying concentrations (25–100 µl of 1 mg/ml) of vinblastine. The biotransformation was performed in a liquid nutrient broth medium containing vinblastine (25–100 µl), and Pseudomonas spp. inoculums (50–150 µl) by incubating at 30 °C and 37 °C, respectively for 8 days. The process was optimized for substrate and culture concentrations, pH, temperature, and rotation speed (rpm) for the highest conversion. Analysis using LC–MS/MS confirmed the presence of vincristine as a product of the vinblastine biotransformation by two Pseudomonas spp. P. fluorescens 2421 showed a faster conversion rate with 95% of vinblastine transformed within 24 h than P. aeruginosa 8485, which demonstrated a conversion rate of 92% on the 8th day. From LC–MS/MS analysis, the optimal conditions for the reaction were determined as vinblastine (25 µl), microbial inoculums (150 µl or 200 × 106 and 210 × 106 CFU/ml), pH 7.4, rotation speed of 180 rpm, and temperatures of 30 °C and 37 °C with incubation time of 8 days. The vincristine produced exhibited potent antiangiogenic activity in the CAM assay reducing the thickness and branching of blood vessels in a dose-dependent manner. The study concludes that both Pseudomonas spp. showed promise for vincristine production from vinblastine, without compromising its antiangiogenic properties.

Abstract Anelloviruses are nonpathogenic viruses that comprise a major portion of the human virome. Despite being ubiquitous in the human population, anelloviruses (ANVs) remain poorly understood. Basic features of the virus, such as the identity of its capsid protein and the structure of the viral particle, have been unclear until now. Here, we use cryogenic electron microscopy to describe the first structure of an ANV-like particle. The particle, formed by 60 jelly roll domain-containing ANV capsid proteins, forms an icosahedral particle core from which spike domains extend to form a salient part of the particle surface. The spike domains come together around the 5-fold symmetry axis to form crown-like features. The base of the spike domain, the P1 subdomain, shares some sequence conservation between ANV strains while a hypervariable region, forming the P2 subdomain, is at the spike domain apex. We propose that this structure renders the particle less susceptible to antibody neutralization by hiding vulnerable conserved domains while exposing highly diverse epitopes as immunological decoys, thereby contributing to the immune evasion properties of anelloviruses. These results shed light on the structure of anelloviruses and provide a framework to understand their interactions with the immune system.

Abstract Cells contain disparate amounts of distinct amino acids, each of which has different metabolic and chemical origins, but the supply cost vs demand requirements of each is unclear. Here, using yeast we quantify the restoration-responses after disrupting amino acid supply, and uncover a hierarchically prioritized restoration strategy for distinct amino acids. We comprehensively calculate individual amino acid biosynthetic supply costs, quantify total demand for an amino acid, and estimate cumulative supply/demand requirements for each amino acid. Through this, we discover that the restoration priority is driven by the gross demand for an amino acid, which is itself coupled to low supply costs for that amino acid. Demand from metabolic requirements dominate the demand-pulls for an amino acid, as exemplified by the largest restoration response upon disrupting arginine supply. Collectively, this demand-driven framework that drives the amino acid economy can identify novel amino acid responses, and help design metabolic engineering applications.

Artificial intelligence (AI) is increasingly being applied to wastewater treatment to enhance efficiency, improve processes, and optimize resource utilization. This review focuses on objectives, advantages, outputs, and major findings of various AI models in the three key aspects: the prediction of removal efficiency for both organic and inorganic pollutants, real-time monitoring of essential water quality parameters (such as pH, COD, BOD, turbidity, TDS, and conductivity), and fault detection in the processes and equipment integral to wastewater treatment. The prediction accuracy (R2 value) of AI technologies for pollutant removal has been reported to vary between 0.64 and 1.00. A critical aspect explored in this review is the cost-effectiveness of implementing AI systems in wastewater treatment. Numerous countries and municipalities are actively engaging in pilot projects and demonstrations to assess the feasibility and effectiveness of AI applications in wastewater treatment. Notably, the review highlights successful outcomes from these initiatives across diverse geographical contexts, showcasing the adaptability and positive impact of AI in revolutionizing wastewater treatment on a global scale. Further, insights on the ethical considerations and potential future directions for the use of AI in wastewater treatment plants have also been provided. HIGHLIGHTS Artificial intelligence (AI) has immense potential to optimize the wastewater treatment processes.; Prediction, real-time monitoring, and fault detection using AI have been reviewed.; Cost-effectiveness of implementing AI in wastewater treatment has been discussed.; Adaptability and impact of AI in wastewater treatment globally has been highlighted.;

Objective: We studied the temporal course of hypothalamic–pituitary–adrenal (HPA) dysfunction in patients with coronavirus disease 2019 (COVID-19). Methods: Three hundred and two patients (median age 54 years (interquartile range (IQR) 42–64), 76% males) were recruited. The HPA axis was evaluated by morning cortisol and adrenocorticotrophic hormone (ACTH) at admission (n = 232). Adrenal insufficiency (AI) during acute illness was defined using a morning cortisol

Abstract Objective Proteasomes are conserved proteases crucial for proteostasis in eukaryotes and are promising drug targets for protozoan parasites. Yet, the proteasomes of Entamoeba histolytica remain understudied. The study’s objective was to analyse the differences in the substrate binding pockets of amoeba proteasomes from those of host, and computational modelling of β5 catalytic subunit, with the goal of finding selective inhibitors. Results Comparative sequence analysis revealed differences in substrate binding sites of E. histolytica proteasomes, especially in the S1 and S3 pockets of the catalytic beta subunits, implying differences in substrate preference and susceptibility to inhibitors from host proteasomes. This was strongly supported by significantly lower sensitivity to MG132 mediated inhibition of amoebic proteasome β5 subunit’s chymotryptic activity compared to human proteasomes, also reflected in lower sensitivity of E. histolytica to MG132 for inhibition of proliferation. Computational models of β4 and β5 subunits, and a docked β4-β5 model revealed a binding pocket between β4-β5, similar to that of Leishmania tarentolae. Selective inhibitors for visceral leishmaniasis, LXE408 and compound 8, docked well to this pocket. This functional and sequence-based analysis predicts differences between amoebic and host proteasomes that can be utilized to develop rationally designed, selective inhibitors against E. histolytica.

The agriculture industry has an enormous influence on a nation's economy. Loss of yield due to plant diseases remains a reason, reducing crop quantity and quality. Incorrect diagnosis of crop diseases can result in improper application of chemical pesticides, which promotes immune microbial strains, raises expenses, and triggers fresh outbreaks that are harmful to the economy and the ecosystem. Despite the potential of Machine Learning (ML) and Deep Learning (DL) approaches in plant disease detection, their limited effectiveness results in poor or late disease detection. Resolving this issue is critical, requiring the development of more accurate disease detection methods. This research introduces an innovative approach for the detection of apple leaf diseases utilizing the CNN-based Inception-v3 model. The dataset comprises images taken on location without having any control over the image-capturing settings may provide better relevance to real-world scenarios. The proposed method integrates canny edge detection and watershed transformation to achieve accurate image segmentation, thereby enhancing the identification of disease regions. Additionally, exploratory data analysis was performed, and channel distributions were visualized to understand the dataset's characteristics. To ensure robust evaluation, the model's performance underwent stratified 5-fold cross-validation. The model classified plant images with 84.60% precision, 87.40% recall, 85.00% F1-score, and 94.76% accuracy. Experimental results substantiate the efficacy of the proposed approach, surpassing existing methods in disease classification.

Objective: This review aims to explore the role of physical activity as an integral palliative care strategy in managing deep vein thrombosis (DVT), providing a comprehensive analysis and practical insights for clinicians. Methods: A thorough review of relevant literature was conducted, encompassing studies, clinical trials, and expert opinions that examine the relationship between physical activity and palliative care from the perspective of DVT. The search included databases such as PubMed, PEDro, and Scopus, with an emphasis on articles published within the last decade. Results: The review highlights the multifaceted benefits of incorporating physical activity into the palliative care approach for individuals with DVT. Physical activity has been effective in enhancing overall well-being, alleviating symptoms, and contributing to the holistic management of DVT-related complications. In addition, the literature underscores the importance of personalized exercise regimens tailored to the patient’s condition, ensuring safety and effectiveness. Conclusion: This comprehensive review underscores the significance of physical activity as a pivotal element in palliative care for individuals with DVT. Integrating personalized exercise regimens into the management strategy offers a holistic approach that addresses the physical and psychosocial aspects of DVT. As clinicians navigate the complexities of DVT palliative care, a thorough and timely incorporation of physical activity can significantly contribute to enhancing the overall quality of life for affected individuals.

Background and Aims: Nearly half of the patients following breast cancer surgery experience postoperative pain. The interfascial plane for the pectoral nerve (PECS) block, along with dexmedetomidine, can alleviate this pain. Methods: After institutional ethics committee clearance and written informed consent, this randomised, double-blind study was conducted on 60, 18–60 years female patients, who were scheduled for modified radical mastectomy (MRM) under general anaesthesia. Patients were randomised into Group L (20 ml of 0.25% levobupivacaine) and Group DL (20 ml of 0.25% levobupivacaine with 0.5 µg/kg of dexmedetomidine). After resection of the tumour and securing haemostasis, under strict aseptic precaution, 10 ml of the study drug was injected under direct vision between the pectoralis major and pectoralis minor and 10 ml between pectoralis minor and serratus anterior muscles by the operating surgeon (direct PECS block). The primary outcome was to compare the duration of analgesia. Normally distributed variables were compared using Student’s t-test, and non-normally distributed variables were compared using the Mann–Whitney U-test. Qualitative data were analysed using Chi-square/Fisher’s exact test. Statistical significance was kept at P < 0.05. Results: The median time of the first analgesic requirement was 8 [inter-quartile range (IQR): 6–8] h in Group L and 18 (IQR: 16–20) h in Group DL (W = 17.000, P < 0.001). The mean total opioid consumption of Group L was 12.53 [standard deviation (SD): 2.29] mg in the first 24 h and 6.93 (SD: 1.89) mg in Group DL. Conclusion: Adding 0.5 μg/kg dexmedetomidine to 20 ml of levobupivacaine enhances the duration of analgesia of direct PECS block in patients undergoing MRM.

Aim: The aim of the study was to assess the association of nutritional status and dental caries in children at an orphanage in Raichur city, Karnataka. Materials and Methods: A specially designed structured questionnaire was administered to a total of 101 children of the orphanage to gather demographic details, dietary habits, sugar exposure, and oral hygiene practices. The sweet score was recorded as given by Nizel and Papas, body mass index (BMI) was assessed using the Centers for Disease Control 2000, growth charts, dental caries, and odontogenic infections were recorded using decayed missing filled teeth in deciduous dentition (dmft)/Decayed Missing Filled Teeth in permanent dentition (DMFT) and pufa/PUFA (Pulpal involvement, Ulceration, Fistula, and Abscess) index (Monse et al., 2010), respectively. Results: A total of 101 participants were enrolled in the study including children aged 6–15 years old with a mean age of 10.67 ± 2.74 years. A statistically significant relation was found between the duration of stay in an orphanage and the prevalence of dental caries (P < 0.05). A statistically significant positive correlation was found between the duration of stay in the orphanage and BMI (0.382) dmft/DMFT (0.203). In addition, a statistically significant positive correlation was also observed between dmft/DMFT and pufa/PUFA. Conclusion: The study showed caries to be primarily associated with the sugar exposure and dietary habits, whereas untreated dental decay was the main cause of odontogenic infections. The untreated caries PUFA ratio was 13.98% with only one filled component, indicating the unmet needs for decayed teeth and lack of awareness and access to preventive and curative dental care facilities by the children of the orphanage.

Abstract Clothing is an essential aspect of our daily lives, but it comes with a high environmental cost. The production and disposal of clothing contribute to pollution, greenhouse gas emissions, and the depletion of natural resources. However, recycled clothing presents an opportunity to reduce the impact of the fashion industry on the environment. The present study aims to investigate the impact of product-related factors, personal factors, promotional factors, social factors, and environmental and economic factors on recycled clothing buying behaviour. The data for analysis was collected using a survey method both online and offline from a sample of 420 selected through convenient sampling. Using SEM analysis, the study identified that all five factors influenced recycled clothing buying behaviour. Notably, it was found that among the factors considered promotional factors exhibited a pronounced effect on recycled clothing buying behaviour. Intriguingly product product-related factors did not show a significant influence on buying behaviour. The result of the study provides new insights into the existing literature in the context of the study.

Abstract This study evaluates the consumers’ views on various security measures in e-commerce platforms and determines their impact on the trusting beliefs of consumers, which may further lead to an intention to use e-commerce platforms. The study also investigates the moderating effects of gender, age, and the frequency of e-commerce platform use on the proposed model. A total of 780 respondents were used for the study. We used structural equation modeling (SEM) to analyze the proposed trust-based model. The findings indicate a strong positive impact of information integrity and information confidentiality on the consumers’ trusting beliefs. In addition, the study indicates the strong mediating effect of trusting beliefs with the association between information integrity, information confidentiality, and behavioral intention to use e-commerce platforms. A moderating effect of frequency of use on the relationship between perceived information confidentiality and preventing unauthorized secondary data usage on trusting beliefs was found to be significant. This research underwent an in-depth examination of different security aspects that e-commerce firms should consider in order to develop the trusting beliefs of consumers in e-commerce environments.

Abstract Background India is experiencing a rising burden of chronic disease multimorbidity due to an aging population and epidemiological transition. Older adults residing in urban slums are especially vulnerable due to challenges in managing multimorbidity amid deprived living conditions. This study aimed to assess the prevalence of multimorbidity, associated health literacy, and quality of life impact in this population. Methods A community-based cross-sectional study was conducted among 800 adults aged ≥ 65 years in an urban slum in Gujarat, India. Data on sociodemographics, physical and mental health conditions, health literacy (HLS-SF-47), quality of life (Short Form-12 scale), and social determinants of health were collected. Multimorbidity is ≥ 2 physical or mental health conditions in one person. Results The prevalence of multimorbidity was 62.5% (500/800). Multimorbidity was significantly associated with lower physical component summary (PCS) and mental component summary (MCS) scores on the SF-12 (p

Abstract Background Ohtahara syndrome is a progressive developmental and epileptic encephalopathy that manifests in the early infantile period. This rare condition is characterized by intractable seizures, psychomotor retardation, and poor prognosis. To date, there are a handful of case reports regarding the anesthetic management of children with Ohtahara syndrome. However, limited reports exist of patients with Ohtahara syndrome who present with difficult airways. This report describes our airway findings and general anesthetic management of a pediatric patient with Ohtahara syndrome undergoing diagnostic bronchoscopy for severe inspiratory stridor. Case presentation A 14-month-old, 9 kg, male patient with Ohtahara syndrome presented with a year-long history of severe inspiratory stridor and was scheduled for bronchoscopy with lavage. On exam, the patient had noisy breathing, was non-verbal with developmental delay, and had poor head control with significant central hypotonia. The patient was induced with ketamine and general anesthesia was maintained with propofol. Bronchoscopic evaluation was completed uneventfully and revealed a diagnosis of laryngotracheomalacia. The patient’s breathing was maintained spontaneously throughout the procedure and no seizures were noted. In the post anesthesia care unit, the patient’s respiratory and cardiovascular function were stable. Conclusions This report documents the unusual finding of severe inspiratory stridor in a 14-month-old child diagnosed with Ohtahara syndrome and our anesthetic management during their diagnostic bronchoscopy. Currently, documentation of complex airway pathology present in patients with Ohtahara syndrome is limited and should be further evaluated. This will assist pediatric anesthesiologists as these patients may require careful preoperative assessment, thoughtful airway management, and surgical alternatives on standby.

OBJECTIVES: Both high and low levels of occupational physical activity are associated with back pain. Thus, there might be a “sweet- and sour-spot” of occupational physical activity for back pain. Our aim was to investigate if there exists an occupational physical activity “sweet- (lowest risk) and sour-spot” (highest risk) for back pain. METHODS: A total of 396 eldercare workers from 20 Danish nursing homes participated. Occupational physical activity was measured between 1–4 working days using thigh-worn accelerometry. Back pain intensity was reported monthly on a scale from 0–10 over 1-year. A zero-inflated mixed-effects model was developed regressing occupational physical activity against back pain, adjusted for confounders. The “sweet- and sour-spot” were defined as the occupational physical activity compositions (sitting, standing, light, and moderate-to-vigorous) associated with the 5% lowest and highest risk for back pain, respectively. RESULTS: The composition associated with the lowest risk of back pain – the “sweet-spot”– consisted of 71% worktime spent sitting, 18% spent standing, 5% spent on light physical activity and 6% spent on moderate-to-vigorous physical activity. The composition associated with highest risk for back pain –the “sour-spot”– consisted of 8% worktime spent sitting, 66% spent standing, 4% spent on light physical activity, and 21% spent on moderate-to-vigorous physical activity. CONCLUSIONS: The “sweet-spot” of occupational physical activity for back pain among eldercare workers involves more sitting and light physical activity time, while the “sour-spot” involves more standing and moderate-to-vigorous physical activity time. Research on the occupational physical activity “sweet- and sour-spot” is needed.

In the present study, MnO2 nanoparticles were synthesized using Citrus limetta peels extract and functionalized by chitosan polymer. Surface morphology analysis of chitosan functionalized MnO2 nanoparticles was carried out using a scanning electron microscope (SEM) and transmission electron microscope (TEM), which revealed that the synthesized nanoparticles were spherical, with a size range of 14–24 nm. Energy dispersive X-ray analysis and elemental mapping were used to observe Mn, O, C, H, and N. Fourier-transform infrared spectroscopy confirmed the presence of hydroxyl, carboxyl, and amino groups on the surface of the nanoparticles. The kinetics and isotherms were compared and it was found that the pseudo-second-order and Langmuir isotherm were the best fit, with R2 values of 0.99. The thermodynamic study demonstrated that the adsorption was endothermic and spontaneous. These findings indicate that chitosan functionalized nanoparticles have a better Pb(II) removal efficiency (94.40%), making them an eco-friendly and cost-effective alternative for wastewater treatment. HighlightsChitosan functionalized nanoadsorbent was synthesized through green route.Sorption mechanism explored through isotherm, kinetics, and thermodynamic models.Synthesized adsorbent showed high Pb(II) removal capacity.

Background: Retinal vein occlusion (RVO) is one of the most common causes of retinal vascular disease, second to diabetic retinopathy. We aimed to compare the lamina cribrosa thickness (LCT) of patients with unilateral branch RVO (BRVO) versus healthy individuals. Materials and Methods: This was a hospital-based, prospective, cross-sectional, and comparative study. Participants were newly diagnosed RVO cases (n = 25) and apparently normal age-matched healthy controls (n = 25). All the participants underwent systemic and comprehensive ophthalmic examination, including refraction and enhanced depth imaging optical coherence tomography. Relevant parameters were compared between the groups using the independent t-test. Statistical significance thresholds were set at a P < 0.05. Results: The mean age of cases (66.7% female) and controls (52% female) was 55.9 ± 7.4 and 59.4 ± 7.0 years, respectively, (P = 0.089). The mean LCT of the affected eyes in cases (176.6 ± 28.3 μm) was significantly lower compared to the unaffected eyes of cases (200.6 ± 33.1 μm, P = 0.008) and control eye (230.9 ± 36.9 μm, P = 0.001). Conclusions: A thinner lamina cribrosa (LC) was observed in both eyes of unilateral RVO patients compared with healthy, nonglaucomatous subjects’ eyes. The role of LCT as a local mechanical factor in the pathogenesis of BRVO and their relationship to systemic factors merits further investigation.

Background: Ventilator-associated pneumonia (VAP) in acute respiratory distress syndrome patients is expected in the setting of prolonged mechanical ventilation due to abridged immunity and dysregulation of the microorganisms inhabiting the oral cavity. We conducted this study to identify the spectrum of microorganisms causing VAP in patients admitted to the medicine intensive care unit (MICU) and their antibiotic susceptibility patterns. Materials and Methods: We conducted a retrospective cross-sectional laboratory-based study from January 2021 to April 2021. Our cohort included patients with respiratory distress who were admitted to the MICU. We observed the incidence of VAP and the risk factors responsible for multidrug resistance (MDR) microorganisms in the MICU, along with 250-day survival in the existence of specific comorbidities along with VAP. Results: Clinical charts of patients (n = 366) admitted to the MICU between January 2021 and April 2021 were used. The mean age of patients admitted to MICU was 57.3 ± 18.7 years with a male predominance (n = 252, 68.8%). VAP was diagnosed in 69.1% (n = 253) of patients, and the most common microorganism in our cohort was Klebsiella pneumoniae (n = 78, 30.8%), followed by Acinetobacter spp. (n = 77, 30.4%). None of the K. pneumoniae isolates (n = 0/78) and only a minority of Acinetobacter spp. (n = 4/77, 5.2%) and Pseudomonas aeruginosa isolates (n = 8/54, 14.8%) were susceptible to fluoroquinolones. A higher proportion of K. pneumoniae (n = 1/78, 1.3%), Acinetobacter spp. (n = 2/77, 2.6%), and P. aeruginosa isolates (n = 9/54, 16.7%) were susceptible to aminoglycosides. The incidence rate of MDR microorganisms among the 253 patients diagnosed with VAP was 92.8% (n = 219/253). Conclusion: There is a high prevalence of multidrug resistance (MDR) isolates among those causing VAP in the MICU setting. Knowing the broad spectrum of causative pathogens and their susceptibility to various antibiotics may guide the physician in judicious and appropriate use of antibiotics for treatment.

Objectives: To determine the prevalence and predictors of loneliness and its associations with health behaviors among elderly adults in Gujarat, India. Methodology: This community-based cross-sectional study included 250 participants aged ≥60 years. Loneliness was measured using the UCLA Loneliness Scale. Associations with socio-demographic, health, and social factors were explored through regression models. Health behaviors were compared between lonely and non-lonely groups. Results: The prevalence of moderate and severe loneliness was 24% (n = 60) and 16% (n = 40), respectively. 40% (n = 100) were found to be lonely. Widowhood (55/125, OR 3.67), living alone (75/125, OR 1.85), social isolation (90/125, OR 2.38), recent bereavement (68/125, OR 1.69), depression (85/125, OR 6.52), and disability (70/125, OR 6.35) were significant predictors of loneliness (P < 0.05). Lonely elders had poorer diet, exercise, sleep, increased smoking, screen time, reduced medical checkups, and social engagements versus non-lonely peers (P < 0.05). Conclusion: Loneliness was highly prevalent among 40% of elderly Indians and strongly linked to adverse health behaviors. Interventions promoting social connectedness, counseling, and peer support are recommended.

This article investigates the current institutional arrangement concerning water governance in Nainital, India, located in the Western Himalayas. It assesses the availability of water resources, the functioning of the supply system, and sheds light on the role of institutions in managing water resources, supply, and distribution. Through qualitative methods (such as focus group discussions and key informant interviews with officials from water management institutions, citizens, etc.) supplemented by a literature review, the study reveals a complex network of institutions and stakeholders involved in water management. This complexity results in overlapping jurisdictions, leading to accountability gaps and various issues. The study identifies that in Nainital, existing institutions operate independently, impacting water governance in terms of water supply, resources, and environmental aspects. Considering the fragile biophysical environment of Nainital, the study also recommends integration of nature-centric approaches into institutional frameworks, which can be helpful in improving the resilience of water systems and promoting sustainable water governance. HIGHLIGHTS Issues and challenges in efficient water management.; Impact of overlapping and mismanagement of institutions on water supply, resources, and environment.; The integration of nature-centric approaches into institutional frameworks can be helpful in enhancing the effectiveness of water management authorities and improving environmental conditions.;

Objectives Post-coronavirus disease 2019 (COVID-19) symptoms were widely reported.However, data on post-COVID-19 conditions following infection with the Omicron variant remained scarce. This prospective study was conducted to understand the prevalence, patterns, and duration of symptoms in patients who had recovered from COVID-19. Methods A prospective study was conducted across 11 districts of Delhi, India, among individuals who had recovered from COVID-19. Study participants were enrolled, and then returned for post-recovery follow-up at 3 months and 6 months interval. Results The mean age of study participants was 42.07 years, with a standard deviation of 14.89 years. The majority of the participants (79.7%) reported experiencing post-COVID-19 symptoms. The most common symptoms included joint pain (36.0%), persistent dry cough (35.7%), anxiety (28.4%), and shortness of breath (27.1%). Other symptoms were persistent fatigue (21.6%), persistent headache (20.0%), forgetfulness (19.7%), and limb weakness (18.6%). The longest duration of symptom was observed to be anxiety (138.75±54.14 days), followed by fatigue (137.57±48.33 days), shortness of breath (131.89±60.21 days), and joint pain/swelling (131.59±58.76 days). At the first follow-up visit, 2.2% of participants presented with abnormal electrocardiogram readings, but no abnormalities were noticed during the second follow-up. Additionally, 4.06% of participants exhibited abnormal chest X-ray findings at the first follow-up, which decreased to 2.16% by the second visit. Conclusion The most frequently reported post-COVID-19 symptoms were joint pain, dry cough, anxiety and shortness of breath. These clinical symptoms persisted for up to 6 months, with evidence of multi-system involvement. Consequently, findings highlighted the need for long-term follow-up during the post-COVID-19 period.

Once correctly indicated, endodontic retreatment requires the preservation of dental components. Effective treatment of teeth with severe damage to the structure of the tooth relies not only on successful endodontic treatment but also on timely postendodontic tooth repair after the same endodontic. Furthermore, for teeth with intracanal posts, the evolution of endodontic procedures and materials has decreased the indication of surgical treatment. Underneath an undamaged crown is a typical clinical occurrence of broken coronal tooth structure. The tooth can be repaired with a post and core if the underlying root is in good condition, and then, the crown is refabricated. This article outlines a method for the aforementioned scenario that makes use of the current unbroken crown. The entire crown was later rescued, and a damaged post and core were also discovered in the canal. The retrieved metallic post was re-cemented in the post space then the undamaged crown was adjusted to fit it, and the opposing arch maintained occlusion. Next, a composite resin that can be dual-cured and built up was poured into the crown, molding it to fit onto the broken tooth. As we know, the core buildup material has a property of dual curing that means it can be self-cured as well as light-cured. Hence, we waited and allowed it to get set by itself chemically. Then, after we carefully removed the crown from over it, a brand-new composite resin core was discovered and adhered to the tooth structure after that we light-cured it for complete the setting process. After that, dual-cured core build-up composite resin was used to re-cement the crown to the core. Even after a year of follow-up, the method of strengthening the tooth’s core and restoring it with the current crown was shown to be effective.

Abstract Hypokalemia is a common issue in clinical settings, often indicating underlying systemic conditions that require careful evaluation. This study presents three cases where hypokalemic paralysis served as the initial symptom of systemic diseases. Key evaluation methods included clinical history, physical examination focusing on volume status, and acid–base assessment. The cases highlight the diverse etiologies of hypokalemia, including primary hyperaldosteronism, Sjogren’s syndrome, and Crohn’s disease.

Abstract Background The World Health Organization (WHO) reports that Asia and Africa have the highest Chronic Liver Disease (CLD) mortality rate. Cirrhosis, responsible for 22.2 fatalities per 100,000 people, is India’s 10th most common cause of mortality. The increasing prevalence of chronic liver disease necessitates a study to identify predictive factors for patients who visit the emergency department. Identifying elements that enhance the predictive value of mortality in unstable patients with CLD complications is important in emergency departments. This study aims to determine Clinical and Laboratory Parameters as mortality predictors in adult chronic liver disease patients. Methodology The study was conducted at the emergency department of a tertiary healthcare center in Northern India. Patients with chronic liver disease above 18 years of age who satisfied the inclusion criteria were clinically evaluated. Clinical and demographic details were collected, and data was analyzed. Results Two hundred thirty-six patients were enrolled. The mean age was 50.77 ± 14.26 years. 78.4% of the participants were men. Abdominal distension, affecting 59.7% of patients, was the most common presenting ailment, followed by melena and hematemesis, affecting 41.9% and 32.6%, respectively. The mean stay in the emergency department was 10.29 ± 8.10 h. Refractory septic shock, the leading cause of mortality, accounts for 69.2% of all deaths, alongside grade 4 hepatic encephalopathy and massive Upper Gastrointestinal (UGI) bleeding, as identified in our study. Factors such as altered mental sensorium, high respiratory rate, low SpO2, increased heart rate, low systolic blood pressure, low diastolic blood pressure, and low Glasgow Coma Scale (GCS) on Emergency Department (ED) arrival are significantly associated with mortality. Conclusions Chronic liver disease, a prevalent condition in India, most commonly seen in middle aged men and lower socioeconomic groups. The parameters independently associated with mortality in our study were presence of altered mental sensorium, Glasgow coma scale, Child Pugh class and need for ICU admission. Understanding the presentation pattern, and mortality predictors can help ED physicians in managing acute events and follow-ups.

Abstract The present work describes the development of TiO2/SeO2 nanostructure as a potential candidate for visible light photocatalysis as well as selective fluorophore for the sensing of picric acid. The obtained nanostructure consists of uniform globular nanoparticles having approximate size of 170 nm and possess an optical band gap of 2.33 eV with absorption maxima at 473 nm. The photocatalyst was able to achieve 90.34% degradation efficiency for 2, 4-dichlorophenol (2,4-DCP) with rate constant of 0.0046 min−1 in the visible region. Further the nanostructure was able to serve as a selective fluorophore for sensing of Picric acid portraying more than 95% of fluorescence quenching when the concentration of PA is 10–4 M. Theoretical calculations indicate the interaction of organic pollutants with the nanostructure and reveal that both picric acid (− 66.21 kcal/mol) and 2,4-DCP (− 12.31 kcal/mol) possess more negative binding energy values demonstrating a strong interaction of both with the nanostructure, making it suitable for the degradation as well as sensing of organic pollutants. Thus this study explains the potential of prepared catalyst for waste water treatment.

Abstract Background Low- and middle-income countries face a disproportionate impact of sexual health problems compared to high-income countries. To address this situation proper interpersonal communication skills are essential for clinician to gather necessary information during medical history-taking related to sexual health. This study aimed to evaluate the interrater reliability of ratings on sexual health-related interpersonal communication and medical history-taking between SPs and trained HCP faculty for health care professional students. Methods We conducted a cross-sectional comparative study to evaluate the interrater reliability of ratings for sexual health-related interpersonal communication and medical history-taking. The data were collected from medical and nursing students at Muhimbili University of Health and Allied Sciences, who interviewed 12 Standardized Patients (SPs) presenting with sexual health issues. The video-recorded interviews rated by SPs, were compared to the one rated by 5 trained Health Care Professional (HCP) faculty members. Inter-rater reliability was evaluated using percent agreement (PA) and kappa statistics (κ). Results A total of 412 students (mean age 24) were enrolled in the study to conduct interviews with two SPs presenting with sexual health concerns. For interpersonal communication (IC), the overall median agreement between raters was slight (κ2 0.0095; PA 48.9%) while the overall median agreement for medical sexual history-taking was deemed fair (κ2 0.139; PA 75.02%). Conclusion The use of SPs for training and evaluating medical and nursing students in Tanzania is feasible only if they undergo proper training and have sufficient time for practice sessions, along with providing feedback to the students.

Abstract Background The cancer burden in Africa is on the rise. A Cancer Training Course on screening, prevention, care, and community education is crucial for addressing a wide range of cancer health issues. When appropriately educated healthcare providers on cancer provide care, patient care improves, and healthcare costs decrease. However, in Tanzania, doctors and nurses receive little or no training in primary cancer care in their bachelor’s program. Aim This study assessed the need and acceptability of a cancer training course for nursing and medical doctor students at the Muhimbili University of Health and Allied Sciences (MUHAS) in Dar es Salaam, Tanzania. Methods This study was a cross-sectional parallel mixed method study during the 3-month follow-up within the larger study on sexual health training for health professionals. The study was a randomized controlled (RCT), single-blind, parallel trial of sexual health training versus a waitlist control among health students at MUHAS in Tanzania. Descriptive analysis was performed to analyze the participants’ demographic information, need, and acceptability of the cancer training courseto determine the frequencies and percentages of their distribution between disciplines. In addition, inductive thematic analysis was performed for the qualitative data. The RCT study was registered at Clinical Trial.gov (NCT03923582; 01/05/2021). Results Data were collected from 408 students (272 medical doctors and 136 nursing students). The median age of the participants was 23 years. Most (86.0%) medical and 78.1% of nursing students reported receiving little to no cancer training. On the other hand, most (92.3%) medical and nursing (92.0%) students were interested in receiving cancer training. Furthermore, 94.1% of medical and 92.0% of nursing students needed a cancer training course in their undergraduate program. In addition, participants said a cancer training course would be important because it would help them improve the quality of cancer care and enhance the quality of life for patients by ensuring early diagnosis and treatment. Conclusion A cancer training course is both highly needed and acceptable to medical and nursing students. Implementation of this cancer training course will improve students’ knowledge and skills and eventually improve the quality of cancer care and patients’ quality of life by ensuring early diagnosis and management.

Chronic kidney disease (CKD), especially in stages III, IV, V patients presenting for surgical removal of parathyroid glands, has special concerns regarding anesthesia. Their renal disease restricts the choice of drugs that can be used for general anesthesia induction and management. Bilateral superficial cervical plexus block (SCPB) under ultrasound guidance can be an alternative mode of anesthesia in parathyroid surgeries in these patients. The aim of the present case series was to evaluate the effectiveness of bilateral SCPB in CKD (stages III, IV, V) patients undergoing parathyroid surgeries in terms of hemodynamic stability, intraoperative and post-operative analgesia, and surgeon’s satisfaction. In the present case series, USG-guided bilateral SCPB was performed under aseptic precautions and 10 mL of local anesthetic was injected on each side. Effect was confirmed with wet swab and blunt pin prick. Then, patient was handed over to the surgeon. Continuous hemodynamic monitoring was done and time of first rescue analgesia was noted. Bilateral SCPB proved to be a good alternative mode of anesthesia for CKD (stages III, IV, V) patients undergoing parathyroid surgeries.

Background: Bone Marrow Aspiration (BMA) and Bone Marrow Trephine Biopsy (BMB) are used to diagnose various hematological disorders. BMA is useful for study of cell cytology; material can also be used for ancillary tests like cytogenetics, flow cytometry, which improves the diagnostic utility. BMB allows complete assessment of marrow architecture along with pattern of distribution of abnormal infiltrates. Thus, BMA & BMB serve as complimentary procedures to diagnose various hematological disorders if performed simultaneously. Material and methods: Hospital based prospective study done within the duration of 2 years starting from August 2020 to August 2022. All the patients who underwent bone marrow examination at Department of Pathology, Tertiary Care Hospital of Ahmedabad, Gujarat, India were included. BMA was done using Salah needle under aseptic precautions from posterior superior iliac spine. 8-10 aspirate smears were prepared, stained by Romanowsky stains. BMB was also done in all cases using Jamshidi needle from same site. The biopsy was processed and slides were stained by Hematoxylin and Eosin (H&E). Evaluation was done by two pathologists. Results: Total 106 patients were included. Maximum number of patients belonged to 50-59 years age group followed by 60-69 years of age with M:F ratio of 1.6:1. Leading clinical feature was weakness/fatigue followed by pallor/anemia & fever. Megaloblastic Anemia (38%) was the most common hematological disorder in study population followed by Acute Leukemia (11%). 80% positive correlation between BMA & BMB was identified to diagnose various disorders. Conclusion: Megaloblastic anemia is the most common hematological disease in study population & can present with variable cytopenia. Accurate diagnosis depends on BMA & BMB evaluation along with peripheral smear & biochemical immunoassays. The role of BMA & BMB remains untouched in the diagnosis of various hematological disorders in-spite of newer methods like immunohistochemistry, flow cytometry, cytogenetics and molecular assays.

Introduction: Conventional teaching in microbiology revolved around the study of microorganisms without clinical relevance. Therefore, a New Competency-based Undergraduate (UG) Medical curriculum (New CBME) was rolled out in the academic year 2019 to make Indian Medical Graduates more clinically competent yet globally relevant. Aim: To assess the impact of the change in curriculum on students’ performance and desired educational outcomes before and after the implementation of the new curriculum. Likewise, the study aimed to analyse the experiences and reflections of medical teachers towards these amendments. Materials and Methods: A cross-sectional observational study was conducted on 82 students from the second year Bachelor of Medicine, Bachelor of Surgery (MBBS) with a traditional curriculum and 74 with the new Competency-based Medical Education (CBME) curriculum at the Department of Microbiology, Smt. B.K. Shah Medical Institute and Research Centre, Piparia, Vadodara, Gujarat, India, between February 2020 and November 2021. In both batches, topics from core as well as non core areas of various systems were included along with the Attitude, Ethics and Communication (AETCOM) modules. A comparison of both groups was done, and Chi-square values and p-values were calculated. Results: The batch with the new CBME curriculum was able to provide a provisional diagnosis for a case-based question better than the Traditional batch {n=60/74 (81%) vs n=44/82 (54%), p-value=0.0005, significant}. However, the correct aetiology, pathogenesis, and laboratory diagnosis were written better in the traditional batch compared to the new one, n=44/82 (54%) vs n=24/74 (32%). Regarding the AETCOM skills, the new batch had a better understanding of proper communication and ethics, i.e., 73/74 (99%), p-value

Autologous platelet-rich plasma (PRP) enhances the recruitment, proliferation, and differentiation of cells involved in tissue regeneration. Platelets contain a number of growth factors (GFs) including platelet-derived GFs and transforming GF which stimulate the proliferation of mesenchymal cells and vascular endothelial GFs and fibroblast GF which stimulate new blood vessel formation. This study evaluates the efficacy of intralesional injection of PRP in erosive lesions of the oral cavity. Five patients who attended the dental outpatient department of a tertiary care hospital were selected irrespective of age and sex diagnosed with erosive lichen planus, pemphigus, and three with desquamative gingivitis. Initial assessment including blood investigations and evaluation of extent, severity, activity, and pain was done. Autologous was prepared from 30 milliliters of whole blood collected into a 350 ml blood collection bag after modifying the anticoagulant to whole blood ratio. A soft spin followed by a hard spin in Thermo Scientific™ Heraeus™ Cryofuge™ was used for PRP preparation. On the same day, 0.5 mL PRP was directly injected onto the base and edge of the erosions using a 31 gauge needle. Patients were followed up and evaluated weekly. In pemphigus and desquamative gingivitis, PRP therapy relieved pain, burning sensation, and bleeding which was proven from Visual Analog Scale score and severity score. No adverse reactions were noted in patients. Autologous PRP poses no risk of allergic reaction and natural collagen is formed in response to the presence of activated platelets. The use of PRP is safe, efficient, and economic. The inability to prevent recurrent lesions and the inability to heal the lesion completely are the major drawbacks.

Abstract Auxetic materials have a negative Poisson’s ratio and are of significant interest in applications that include impact mitigation, membrane separations and biomedical engineering. While there are numerous examples of structured materials that exhibit auxetic behavior, the examples of engineered auxetic structures is largely limited to periodic lattice structures that are limited to directional or anisotropic auxetic response. Structures that exhibit a three-dimensionally isotropic auxetic response have been, unfortunately, slow to evolve. Here we introduce an inverse design algorithm based on global node optimization to design three-dimensional auxetic metamaterial structures from disordered networks. After specifying the target Poisson’s ratio for a structure, an inverse design algorithm is used to adjust the positions of all nodes in a disordered network structure until the desired mechanical response is achieved. The proposed algorithm allows independent control of shear and bulk moduli, while preserving the density and connectivity of the networks. When the angle bending stiffness in the network is kept low, it is possible to realize optimized structures with a Poisson’s ratios as low as −0.6. During the optimization, the bulk modulus of these networks decreases by almost two orders of magnitude, but the shear modulus remains largely unaltered. The materials designed in this manner are fabricated by dual-material 3D-printing, and are found to exhibit the mechanical responses that were originally encoded in the computational design engine. The approach proposed here provides a materials-by-design platform that could be extended for engineering of optical, acoustic, and electrical properties, beyond the design of auxetic metamaterials.

Abstract Background Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. Methods Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011–2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. Results Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen’s d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test]

Abstract Background Physical behaviors such physical activity, sedentary behavior, and sleep are associated with mortality, but there is a lack of epidemiological data and knowledge using device-measured physical behaviors. Purpose To assess the feasibility of baseline data collection using the Prospective Physical Activity, Sitting, and Sleep consortium (ProPASS) protocols in the specific context of Saudi Arabia. ProPASS is a recently developed global platform for collaborative research that aims to harmonize retrospective and prospective data on device-measured behaviors and health. Using ProPASS methods for collecting data to perform such studies in Saudi Arabia will provide standardized data from underrepresented countries. Method This study explored the feasibility of baseline data collection in Saudi Arabia between November and December 2022 with a target recruitment of 50 participants aged ≥ 30 years. Established ProPASS methods were used to measure anthropometrics, measure blood pressure, collect blood samples, carry out physical function test, and measure health status and context of physical behaviors using questionnaires. The ActivPal™ device was used to assess physical behaviors and the participants were asked to attend two sessions at (LHRC). The feasibility of the current study was assessed by evaluating recruitment capability, acceptability, suitability of study procedures, and resources and abilities to manage and implement the study. Exit interviews were conducted with all participants. Result A total of 75 participants expressed an interest in the study, out of whom 54 initially agreed to participate. Ultimately, 48 participants were recruited in the study (recruitment rate: 64%). The study completion rate was 87.5% of the recruited participants; 95% participants were satisfied with their participation in the study and 90% reported no negative feelings related to participating in the study. One participant reported experiencing moderate skin irritation related to placement of the accelerometer. Additionally, 96% of participants expressed their willingness to participate in the study again. Conclusion Based on successful methodology, data collection results, and participants’ acceptability, the ProPASS protocols are feasible to administer in Saudi Arabia. These findings are promising for establishing a prospective cohort in Saudi Arabia.

Abstract Background Pain management is a major unmet need in people with rheumatoid arthritis (RA). Although many patients are treated with disease modifying anti-rheumatic drugs (DMARDS), including biologic therapies, many people with RA continue to experience significant pain. We aimed to determine whether performing a comprehensive pain evaluation is feasible in people with active RA receiving conventional DMARDs and biologic therapies. Methods The BIORA-PAIN feasibility study was an open-label, randomised trial, which recruited participants suitable for treatment with biologic therapy. The primary feasibility outcomes were recruitment, randomisation and retention of eligible participants. All participants underwent pain assessment for nociceptive, neuropathic and nociplastic pain during the 12-month study period, with quarterly assessments for VAS (Visual Analogue Scale) pain, painDETECT and QST (quantitative sensory testing). This trial was registered in clinicaltrials.gov NCT04255134. Results During the study period, 93 participants were screened of whom 25 were eligible: 13 were randomised to adalimumab and 12 to abatacept. Participant recruitment was lower than expected due to the COVID-19 pandemic. Pain assessments were practical in the clinical trial setting. An improvement was observed for VAS pain from baseline over 12 months, with a mean (SEM) of 3.7 (0.82) in the abatacept group and 2.3 (1.1) in the adalimumab group. There was a reduction in painDETECT and improvement in QST measures in both treatment groups during the study. Participant feedback included that some of the questionnaire-based pain assessments were lengthy and overlapped in their content. Adverse events were similar in both groups. There was one death due to COVID-19. Conclusions This first-ever feasibility study of a randomised controlled trial assessing distinct modalities of pain in RA met its progression criteria. This study demonstrates that it is feasible to recruit and assess participants with active RA for specific modalities of pain, including nociceptive, neuropathic and nociplastic elements. Our data suggests that it is possible to stratify people for RA based on pain features. The differences in pain outcomes between abatacept and adalimumab treated groups warrant further investigation. Trial registration NCT04255134, Registered on Feb 5, 2020.

Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive and fatal pediatric brain cancer. One pre-requisite for tumor cells to infiltrate is adhesion to extracellular matrix (ECM) components. However, it remains largely unknown which ECM proteins are critical in enabling DIPG adhesion and migration and which integrin receptors mediate these processes. Here, we identify laminin as a key ECM protein that supports robust DIPG cell adhesion and migration. To study DIPG infiltration, we developed a DIPG-neural assembloid model, which is composed of a DIPG spheroid fused to a human induced pluripotent stem cell-derived neural organoid. Using this assembloid model, we demonstrate that knockdown of laminin-associated integrins significantly impedes DIPG infiltration. Moreover, laminin-associated integrin knockdown improves DIPG response to radiation and HDAC inhibitor treatment within the DIPG-neural assembloids. These findings reveal the critical role of laminin-associated integrins in mediating DIPG progression and drug response. The results also provide evidence that disrupting integrin receptors may offer a novel therapeutic strategy to enhance DIPG treatment outcomes. Finally, these results establish DIPG-neural assembloid models as a powerful tool to study DIPG disease progression and enable drug discovery.

Background: Neoadjuvant therapy (NAT) is an important tool for the treatment of patients with breast cancer. The aim of NAT is to make it operable for patients with locally advanced breast cancer, to shrink early-stage tumors – thus allowing for breast conservation. Pathological complete response achieved by post-chemotherapy is an independent factor in the long-term survival of patients. Thus, the histopathological components of post-chemotherapy changes such as cellularity and lymph node (LN) tumor deposits, when combined, help to assess residual carcinoma burden. Aims and Objectives: This study aims to analyze various histopathological changes in the breast after neoadjuvant chemotherapy with the objective of evaluating post-chemotherapy response and residual cancer burden. Materials and Methods: A total of 34 cases of post-chemotherapy modified radical mastectomy specimens were analyzed for pathological response (pCR) and residual cancer burden were evaluated. Tumor cellularity, stromal changes, lymphovascular invasion, and LN involvement were noted. Results: The age group of presentation of 34 cases ranged from 30 to 75 years of age with the mean age being 43.5 years. The most common histomorphological finding was fibrosis/elastosis and vacuolation with 26 (76.5%) and 24 (70.6%) cases, respectively. The number of cases that showed partial pCR was 30 (88.2%) and 1 (2.9%) case showed a pathological complete response which belonged to Stage 0, pathological no response was shown by 3 (8.8%) cases which belonged to Stage II and Stage IV. Conclusion: Post-chemotherapy response of neoadjuvant chemotherapy in breast carcinoma is important for prognosis and predictive information for disease relapse.