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Background: Social determinants of health (SDOH) have been shown to be important predictors of health outcomes. Here we developed methods to extract them from inpatient electronic medical record (EMR) data using techniques compatible with current EMR systems., Methods: Four social determinants were targeted: patient language barriers, employment status, education, and whether the patient lives alone. Inpatients aged 18 and older with records in the Calgary-wide EMR system were studied. Algorithms were developed on the January 2019 hospital admissions (n=8,999) and validated on the January 2018 hospital admissions (n=8,839). SDOH documented as structured data were compared against those extracted from unstructured free-text notes., Results: More than twice as many patients had a note documenting a language barrier in EMR data than in structured data; 12 % of patients indicated by EMR notes to be living alone had a partner noted in their structured marital status. The Positive Predictive Value (PPV) of the elements extracted from notes was high, at 99 % (95 % CI 94.0 %-100.0 %) for language barriers, 98 % (95 % CI 92.6 %-99.9 %) for living alone, 96 % (95 % CI 89.8 %-98.8 %) for unemployment, and 88 % (95 % CI 80.0 %-93.1 %) for retirement., Conclusions: All SDOH elements were extracted with high PPV. SDOH documentation was largely missing in structured data and sometimes misleading., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The digger wasp genus Pseudoscolia Radoszkowski, 1876 is newly reported from India with a new species: Pseudoscolia anuae Saini sp. nov. from the State of Haryana.

Introduction: The revision of International Federation of Gynaecology and Obstetrics staging in 2018 with recommendations to include cross-sectional imaging and a separate stage for node positive disease have opened a lot of uncertainties in implementing the correct treatment approach in these patients. While studies have suggested higher chances of occult para-aortic lymph node (PALN) even with advanced imaging, especially in pelvic node positive disease which tend to recur after pelvic radiation therapy. This study intends to study these patients and isolate the subset who will benefit most from elective PALN irradiation., Methods and Analysis: This is an ongoing multicentric phase III randomised controlled trial with a sample size of 274 subjects in two arms (137 in each arm) to determine the superiority of limited elective para-aortic irradiation compared with no irradiation. Arm one includes radiation to the lower PALN and pelvis; Arm two includes radiation to the pelvis. Concurrent chemotherapy followed by brachytherapy is standard in both arms. Patients with cervical cancer and radiologically positive pelvic LNs aged>18 years and<70 years are screened for the study. The primary endpoint of this study is 3-year disease-free survival. The secondary endpoints include 3-year para-aortic recurrence-free survival, 3-year distant metastasis-free survival, 3-year overall survival, acute and late toxicity, quality of life. Translational study to evaluate systemic immune response by FAPI-PETCT (fibroblast activator protein inhibitor positron emission tomography) and assessment of p16, L1 cell adhesion molecule (L1CAM) and protein death ligand-1 (PDL-1) expression by immunohistochemistry., Ethics and Dissemination: The study has been approved by the institutional ethics committee and will be routinely monitored according to standard guidelines. The results of the study will be published in peer-reviewed scientific journals, presented at conferences and submitted to regulatory authorities., Trial Registration Number: The study was registered on 17 January 2022 under CTRI/2022/01/039495 (http://ctri.nic.in)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate their anti-Mtb efficacy in vitro and in vivo, as well as their acute toxicity. SLMs measured 0.7-0.89 µM in size, with complete in vitro release of OA and UA at 40 and 32 h, respectively. The minimum inhibitory concentration (MIC) of SLMs loaded with OA and UA was 40 µg/mL SLMs + 20 µg/mL OA + 20 µg/mL UA for drug-sensitive Mtb and 80 µg/mL SLMs + 40 µg/mL OA + 40 µg/mL UA for multidrug-resistant (MDR) Mtb. These SLMs showed an efficient reduction in Mtb burden in infected alveolar macrophages. In a murine model of late-stage progressive MDR-TB, aerosolized delivery of SLMs containing OA and UA via a metered-dose inhaler significantly reduced pulmonary bacterial loads and extended survival. In vivo, acute toxicity studies revealed no mortality or signs of toxicity. These findings demonstrate that SLMs are an optimal delivery system for terpenoids, providing potent in vitro and in vivo anti-TB activity with an excellent safety profile.

We developed stable luminescent morpholine-appended copper nanoclusters CuNCs@MorMB with an ultra-small size (<3 nm) and a long emission lifetime (577 ns). They mediate a Fenton-like reaction to produce reactive hydroxyl radicals (˙OH), subsequently depleting antioxidant glutathione levels for cancer chemodynamic therapy (CDT).

Scrofuloderma is most common presentation of cutaneous tuberculosis in India. A 15-years-old immunocompetent male presented with bilateral cervical necrotising lesions and was treated with ATTx9 months, without improvement. Patient was diagnosed with scrofuloderma and ZN staining revealed 2+acid-fast bacilli. Cartridge-based nucleic acid amplification test showed rifampicin resistance. Patient was initiated on shorter regimen, but deferred treatment owing to technical portal problems. After 3 months, neck swelling had enlarged and he was started on multi-drug regimen x24 months. This underlines requisite to consider scrofuloderma in differentials of bilateral cervical lesions and to periodically monitor compliance to prevent subsequent emergence of resistance., Competing Interests: No conflicts of interest., (© 2024 The Authors.)

Aims: Neuronal disorders have affected more than 15% of the world's population, signifying the importance of continued design and development of drugs that can cross the Blood-Brain Barrier (BBB)., Background: BBB limits the permeability of external compounds by 98% to maintain and regulate brain homeostasis. Hence, BBB permeability prediction is vital to predict the activity of a drug-like substance., Objective: Here, we report about developing BBBper (Blood-Brain Barrier permeability prediction) using machine learning tool., Method: A supervised machine learning-based online tool, based on physicochemical parameters to predict the BBB permeability of given chemical compounds was developed. The user-end webpage was developed in HTML and linked with back-end server by a python script to run user queries and results., Result: BBBper uses a random forest algorithm at the back end, showing 97% accuracy on the external dataset, compared to 70-92% accuracy of currently available web-based BBB permeability prediction tools., Conclusion: The BBBper web tool is freely available at http://bbbper.mdu.ac.in., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Inappropriate mealtime behavior (IMB) is a type of feeding challenge within the broader class of food refusal. The purpose of this study was to critically analyze the efficacy of interventions for the treatment of IMB through a meta-analysis of research using single-case experimental designs. We examined the extent to which different interventions resulted in decreases in IMB while also producing increases in food acceptance. This meta-analysis was also used to examine the efficiency of different interventions in achieving clinical significance. We identified 38 studies involving 266 cases in which IMB was treated with a behavioral intervention. The results indicated interventions that combined escape extinction and non-escape extinction had greater effect sizes for both reducing IMB and increasing food acceptance than either escape extinction alone or non-escape extinction alone. However, interventions that included escape extinction were slightly less efficient at decreasing IMB than were interventions that did not include escape extinction. We discuss the implications of these findings and provide recommendations for future research., (© 2024 The Author(s). Journal of Applied Behavior Analysis published by Wiley Periodicals LLC on behalf of Society for the Experimental Analysis of Behavior (SEAB).)

Study Objectives: Idiopathic hypersomnia (IH) is characterized by excessive sleepiness during the day, prolonged sleep at night, and difficulty waking up. The true prevalence of IH is uncertain. The International Classification of Sleep Disorders provides criteria for diagnosing IH; however, the definition has evolved. Managing IH involves using pharmacologic and nonpharmacologic approaches, although the most effective strategies are still unclear. The objective of this scoping review was to identify the extent, range, and nature of the available evidence, identify research gaps, and discuss the implications for clinical practice and policy., Methods: To conduct this review, a comprehensive search was conducted across scientific databases, without any restrictions on the date or study type. Eligible studies examined the effectiveness of pharmacologic and nonpharmacologic treatments for IH and reported the outcomes of these interventions. Data from the studies were screened, analyzed, and synthesized to provide an overview of the available literature landscape., Results: Fifty-one studies were included in this review, which used various methods and interventions. Pharmacological treatments, particularly modafinil, have been frequently studied and have yielded positive results. There is also emerging evidence for alternative medications such as low-sodium oxybate and pitolisant. Nonpharmacological approaches, such as cognitive behavioral therapy for hypersomnia and transcranial direct current stimulation have also shown promise in managing IH., Conclusions: This review highlights the complexity of managing IH symptoms and emphasizes the need for personalized multidisciplinary approaches. Pharmacological interventions are important in managing IH and can be complemented by nonmedication strategies. Larger-scale studies are necessary to advance our understanding of IH and to improve treatment outcomes., Citation: Saini V, Saini S. A scoping review of the evidence on pharmacological and nonpharmacological interventions for idiopathic hypersomnia. J Clin Sleep Med . 2024;20(10):1685-1704., (© 2024 American Academy of Sleep Medicine.)

When applied to functional analysis results, structured visual inspection criteria have resulted in improvements in the levels of agreement between raters as well as earlier identification of the function of challenging behavior. However, multistep criteria can be difficult to apply in real time, which could be a barrier to widespread adoption in practice. This study evaluated a Microsoft-Excel-based functional analysis decision support system (FADSS), which could aid behavior analysts with interpreting functional analysis results. Final overall agreement between the FADSS and post hoc visual inspection was high at 95%. Final overall agreement between the post hoc results generated by FADSS and ongoing results generated by FADSS was acceptable at 81%, representing a 50% increase in efficiency. These results indicate that FADSS could aid behavior analysts when interpreting functional analysis results in real time., (© 2024 Society for the Experimental Analysis of Behavior (SEAB).)

Background:  Autism spectrum disorder (ASD) is a disorder that is manageable but has no cure. Therefore, it is associated with parental stress, which is often not given importance. Early identification and holistic management of children with ASD are needed., Methods: This prospective case-control study, conducted over 18 months, included 111 newly diagnosed autism cases (ages 2-9) from the Child Development Clinic at Shri Mahant Indiresh Hospital, Dehradun, India, diagnosed as per the International Clinical Epidemiology Network (INCLEN) criteria (DSM-V). Controls were 99 typically developing children from a well-baby clinic. Data collection involved administering the Autism Parenting Stress Scale and a predesigned questionnaire to both cases and controls. Parents with psychiatric or mental health issues were excluded., Results: Parents of children with autism exhibited significantly higher stress scores compared to parents of typically developing children. In our study, out of a total of 210 subjects, 52.9% were diagnosed with autism, while 47.1% were controls. Cases were analyzed based on household and socioeconomic background. It was found that 94.6% of the cases showed significant stress levels., Conclusion: ASD significantly impacts parental stress, particularly among families from higher socioeconomic backgrounds and metropolitan areas. This study emphasizes the need for targeted support and interventions to address elevated stress levels and improve family dynamics, especially for parents of higher-functioning children., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Shri Guru Ram Rai Institute of Medical and Health Sciences Institutional Ethics Committee issued approval SGRR/IEC/66/21. This approval has been granted on the assumption that the proposed research work will be carried out in accordance with the ethical guidelines prescribed by the Central Ethics Committee on Human Research (CECHR). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Negi et al.)

Pulmonary arteriovenous malformations (PAVMs) are abnormal vascular connections between the pulmonary arteries and pulmonary veins. Despite their relatively uncommon incidence, PAVMs should be considered in the differential diagnosis of children presenting with cyanosis due to the life-threatening complications posed by paradoxical emboli. The primary management approach involves eliminating the abnormal connections, either through surgical or endovascular methods. We present a case of a five-year-old boy who was seen in the Outpatient Department with cyanosis of the lips and nail beds persisting for eight months. On examination, grade 3 clubbing was noted. Imaging and subsequent angiography revealed multiple bilateral diffuse AVMs, which were treated using an endovascular approach., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Joshi et al.)

Coinfection of pathogenic bacteria and viruses is associated with multiple diseases. During the COVID-19 pandemic, the co-infection of other pathogens with SARS-CoV-2 was one of the important determinants of the severity. Although primarily a respiratory virus gastric manifestation of the SARS-CoV-2 infection was widely reported. This study highlights the possible consequences of SARS-CoV-2 - Helicobacter pylori coinfection in the gastrointestinal cells. We utilized the transfection and infection model for SARS-CoV-2 spike Delta (δ) and H. pylori respectively in colon carcinoma cell line HT-29 to develop the coinfection model to study inflammation, mitochondrial function, and cell death. The results demonstrate increased transcript levels of inflammatory markers like TLR2 (p < 0.01), IL10 (p < 0.05), TNFα (p < 0.05) and CXCL1 (p < 0.05) in pre- H. pylori infected cells as compared to the control. The protein levels of the β-Catenin (p < 0.01) and c-Myc (p < 0.01) were also significantly elevated in pre- H. pylori infected group in case of co-infection. Further investigation of apoptotic and necrotic markers (Caspase-3, Caspase-8, and RIP-1) reveals a necroptotic cell death in the coinfected cells. The infection and coinfection also damage the mitochondria in HT-29 cells, further implicating mitochondrial dysfunction in the necrotic cell death process. Our study also highlights the detrimental effect of pre- H. pylori exposure in the coinfection model compared to post-exposure and lone infection of H. pylori and SARS-CoV-2. This knowledge could aid in developing targeted interventions and therapeutic strategies to mitigate the severity of COVID-19 and improve patient outcomes., Competing Interests: Authors have no conflict of interest to declare., (© 2024 The Authors.)

Introduction: The relative merits of peripheral nerve blocks (PNB) over central neuraxial anaesthesia and the advantages of the above two techniques over general anaesthesia for surgical interventions of the lower limb are well established. The competency of anaesthetic trainees in a high-volume level 1 trauma centre in administering dual ultrasound and nerve stimulator-guided lumbar plexus-sciatic nerve block (DUNLuPS) vs. epidural anaesthesia (EA) was compared by reporting the adequacy of anaesthesia with the two techniques, time taken for the performance of block, time of onset of sensory block (TOSB), and time of onset of motor block (TOMB)., Materials and Methods: This prospective, randomized, study enrolled 92 patients aged 18-80 years with lower limb fractures admitted in trauma triage and scheduled for surgery. The patients were randomly allocated equally into the EA group and the DUNLuPS group. A total of 20 anaesthesia trainees in the third year of residency with clinical experience of more than 15 independent lumbar plexus-sciatic nerve blocks were included in the study. A volume of 20 ml of 0.5% ropivacaine was administered in the lumbar plexus (Shamrock technique) but the volume used for sciatic nerve (subgluteal approach) was varied so that the cumulative dose did not exceed 3 mg/kg. For each block, the onset of nerve blockade was assessed every five minutes, and the assessments continued for an additional 30 minutes after the nerve blocks were finished., Results: Clinical characteristics and adequacy of anaesthesia were comparable, i.e., 95.65% and 93.47% success in the EA (n = 46) and DUNLuPS (n = 46) groups, respectively. Performance time was significantly more in the DUNLuPS group but followed by significantly less TOSB and TOMB. The time for the first analgesic request was 351.63 ± 148.70 minutes in the DUNLuPS group and 147.60 ± 52.65 minutes in the EA group (p < 0.0001)., Conclusion: Both EA and DUNLuPS provide effective and comparable intra-operative anaesthesia for orthopaedic lower limb surgeries (OLLS) when administered by residents with more than two years of experience (third year of residency) in ultrasound-guided regional nerve blocks in a high-volume level 1 trauma centre. Statistically significant differences in the block performance characteristics had no clinical advantage as it was compensated by the faster onset time in the DUNLuPS group. Post-operative pain management was better in the DUNLuPS group, so the practice and conduct of anaesthesia for trauma patients should focus on the establishment of "block rooms" and timely training of residents in the former so that the advantages can be extended to the patient population., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee, Postgraduate Institute of Medical Education and Research issued approval NK/4654/MD/563. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Samra et al.)

The subgenus Corynopus Lepeletier de Saint Fargeau and Brullé, 1835 of the genus Rhopalum Stephens, 1829 is recorded for the first time from India. A new species, viz., Rhopalum (Corynopus) chettalicum, (India: Karnataka) is described. A key and the checklist of all Asian species of the subgenus Corynopus are provided.

Background: The optimal anesthetic strategy for endovascular therapy (EVT) in acute ischemic stroke is still under debate. The aim of this study was to compare the clinical outcomes of patients with isolated posterior cerebral artery (PCA) occlusion stroke undergoing EVT by anesthesia modality with conscious sedation (non-GA) versus general anesthesia (GA)., Methods: Patients from the Posterior CerebraL Artery Occlusion (PLATO) study were analyzed with regard to anesthetic strategy. GA was compared with non-GA using multivariable logistic regression and inverse probability of weighting treatment (IPTW) methods. The primary endpoint was the 90-day distribution of the modified Rankin Scale (mRS) score. Secondary outcomes included functional independence or return to Rankin at day 90, and successful reperfusion, defined as expanded Thrombolysis in Cerebral Infarction (eTICI) 2b to 3. Safety endpoints were symptomatic intracranial hemorrhage and mortality., Results: Among 376 patients with isolated PCA occlusion stroke treated with EVT, 183 (49%) had GA. The treatment groups were comparable, although the GA group contained more patients with severe stroke and lower posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS). On IPTW analysis, there was no difference between groups with regard to ordinal mRS shift analysis (common OR 0.89, 95% CI 0.53 to 1.51, P=0.67) or functional independence (OR 0.84, 95% CI 0.50 to 1.39, P=0.49). There were greater odds for successful reperfusion with GA (OR 1.70, 95% CI 1.17 to 2.47, P=0.01). Safety outcomes were comparable between groups., Conclusion: In patients with isolated PCA occlusion undergoing EVT, patients treated with GA had higher reperfusion rates compared with non-GA. Both GA and non-GA strategies were safe and functional outcomes were similar., Competing Interests: Competing interests: NA reported employment by the American Heart Association. GD reported consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker and stock holdings in RIST and InNeuroCo. JTF reported consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; and stock holdings in Imperative Care and Sim&Cure. UF reported research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; and is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. UF reports patent US11166738B2. DCH reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB from Jacobs Institute; and stock options in Viz AI. CH reported consultancy for Brainomix and Speaker with Stryker. APJ reports consulting with Basking Biosciences; stock options in Gravity Medical Technology; and a patent for a novel stent retriever device licensed to Basking Biosciences. JK reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. DPOK reported grants from the Joachim Herz Foundation. JBK reports grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. JPM reported consulting from Amicus Therapeutics and Boehringer Ingelheim and Speaker with Boehringer Ingelheim. PM reported grants from the University of Lausanne and Swiss National Science Foundation (SNF). MAM reported grants from Medtronic, Stryker, and MicroVention. MaM reported stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology and consulting from MicroVention, Medtronic, and Johnson & Johnson. SN reported consultancy for Brainomix and is a speaker with Boehringer Ingelheim and Pfizer. TNN reported research support from the Society of Vascular and Interventional Neurology (SVIN) and Medtronic and is on the advisory board with Idorsia. RGN reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; and grants from Cerenovus and Stryker. CHN reported compensation (other services) from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen and consultancy for Daiichi Sankyo, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. MP reported grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; and consultancy for Siemens Healthineers. VP reported being a lecturer for Daiichi Sankyo. MR reported consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips and stock holdings in Methinks, Nora, and Anaconda Biomed. PAR reported travel support from Bayer and Bristol Myers Squibb and consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. SAS reported consultancy for Imperative Care, Viz AI, and Penumbra; compensation from Motif Neurosciences (other services); and grants from the National Institutes of Health. AHS reported an ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and Viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in Viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAID, Cerevatech Medical, InspireMD, and PerFlow Medical; and security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. The other authors report no conflicts., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Circulating tumor cells (CTCs) have potential as diagnostic, prognostic, and predictive biomarkers in solid tumors. Despite Food and Drug Administration (FDA) approval of CTC devices in various cancers, the rarity and heterogeneity of CTCs in lung cancer make them technically challenging to isolate and analyze, hindering their clinical integration. Establishing a consensus through comparative analysis of different CTC systems is warranted. This study aimed to evaluate seven different CTC enrichment methods across five technologies using a standardized spike-in protocol: the CellMag™ (EpCAM-dependent enrichment), EasySep™ and RosetteSep™ (blood cell depletion), and the Parsortix® PR1 and the new design Parsortix® Prototype (PP) (size- and deformability-based enrichment). The Parsortix® systems were also evaluated for any differences in recovery rates between cell harvest versus in-cassette staining. Healthy donor blood (5 mL) was spiked with 100 fluorescently labeled EpCAM high H1975 cells, processed through each system, and the isolation efficiency was calculated. The CellMag™ had the highest recovery rate (70 ± 14%), followed by Parsortix® PR1 in-cassette staining, while the EasySep™ had the lowest recovery (18 ± 8%). Additional spike-in experiments were performed with EpCAM moderate A549 and EpCAM low H1299 cells using the CellMag™ and Parsortix® PR1 in-cassette staining. The recovery rate of CellMag™ significantly reduced to 35 ± 14% with A549 cells and 1 ± 1% with H1299 cells. However, the Parsortix® PR1 in-cassette staining showed cell phenotype-independent and consistent recovery rates among all lung cancer cell lines: H1975 (49 ± 2%), A549 (47 ± 10%), and H1299 (52 ± 10%). Furthermore, we demonstrated that the Parsortix® PR1 in-cassette staining method is capable of isolating heterogeneous single CTCs and cell clusters from patient samples. The Parsortix® PR1 in-cassette staining, capable of isolating different phenotypes of CTCs as either single cells or cell clusters with consistent recovery rates, is considered optimal for CTC enrichment for lung cancer, albeit needing further optimization and validation., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background A newborn's admission into the Neonatal Intensive Care Unit (NICU) is one unexpected event capable of causing much stress and anxiety among parents. The current study aims to evaluate and compare parental stress and anxiety levels between mothers and fathers. Methodology This cross-sectional study was conducted in the NICU of a tertiary care center, in Uttarakhand where a total of 306 mothers and fathers were enrolled. Data was compiled using a questionnaire consisting of demographic details of parents and infants' clinical profiles, Parental Stressor Scale (PSS) NICU, and State-Trait Anxiety Inventory (STAI) scales were used to evaluate stress and anxiety, respectively. Results Mothers mean stress levels were greater and statistically significant. The most affected subscale in both parents was the change in parental role (M: 4.4/F: 3.3; p < 0.001). Parents with high trait anxiety also had high state anxiety (M: 51.3/F: 45.5; p < 0.001). Mothers were found to have higher trait and state anxiety than fathers. Conclusion Parents of newborns admitted in the NICU experience significant stress and anxiety. Mothers had higher levels of stress and anxiety; similar findings have been recorded previously in Indian and western literature., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committee issued approval SGRR/IEC//64/21. Consent was obtained or waived by all participants in this study. The Institutional Ethics Committee issued approval with approval number SGRR/IEC//64/21. This approval has been granted on the assumption that the proposed research work will be carried out in accordance with the ethical guidelines prescribed by the Central Ethics Committee on Human Research. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Joshi et al.)

High mortality has been reported in severe cases of COVID-19. Emerging reports suggested that the severity is not only due to SARS-CoV-2 infection, but also due to coinfections by other pathogens exhibiting symptoms like COVID-19. During the COVID-19 pandemic, simultaneous respiratory coinfections with various viral (Retroviridae, Flaviviridae, Orthomyxoviridae, and Picoviridae) and bacterial (Mycobacteriaceae, Mycoplasmataceae, Enterobacteriaceae and Helicobacteraceae) families have been observed. These pathogens intensify disease severity by potentially augmenting SARSCoV-2 replication, inflammation, and modulation of signaling pathways. Coinfection emerges as a critical determinant of COVID-19 severity, principally instigated by heightened pro-inflammatory cytokine levels, as cytokine storm. Thereby, in co-infection scenario, the severity is also driven by the modulation of inflammatory signaling pathways by both pathogens possibly associated with interleukin, interferon, and cell death exacerbating the severity. In the current review, we attempt to understand the role of co- infections by other pathogens and their involvement in the severity of COVID-19., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Rab5B is a small monomeric G protein that regulates early endocytosis and controls signaling pathways related to cell growth, survival, and apoptosis. Dysregulation of Rab5B protein expression has been linked to the development of several cancers such as leukemia, lymphoma, kidney, prostate, ovarian, breast cancer, etc. Our research shows the first attempt to identify inhibitors that can target Rab5B GTPase. In this study, we performed molecular docking using Autodock Vina 1.5.6 and identified eight molecules with docking scores ranging from -9.8 to -10.6 kcal/mol. Thereafter, we examined the pharmacological characteristics of these compounds, and selected compounds were further analyzed for their conformational dynamics and thermodynamic stability using molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA)-based free energy calculations. Notably, our findings revealed that strychnine had the highest binding affinity to Rab5B followed by anonaine, helioxanthin, and taiwanin E, with a ΔG bind value of -21.43, -17.11, -15.11, and -14.09 kcal/mol respectively. The binding free energy calculations showed that Van der Waals interactions are the primary contributor to the binding between Rab5B and the inhibitor. The interaction between the inhibitor and Rab5B was shown to be controlled by certain hot spot residues, including Phe45, Tyr48, Ala64, and Ala30. Overall, we believe that these findings could facilitate the exploration and development of potential hits against Rab5B, subject to optimization and further research., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Coal ash containing significant amount of SiO 2 and Al 2 O 3 is utilized as a catalyst substrate for carbon nanotubes (CNTs) synthesis. Three different types of catalysts were made by impregnating coal ash with cobalt, iron, and nickel. These catalysts were used to produce CNTs through pyrolysis of waste polypropylene followed by chemical vapor deposition. The influence of catalyst type and reaction temperature (700, 800 and 900 °C) on CNTs yield and its quality was studied in detail. The produced CNTs were characterized by thermogravimetric analysis (TGA), Raman scattering and electron microscopes (FESEM and HRTEM). The TGA results revealed that the Ni catalyst produced CNTs with highest yield (266 %) compared to those synthesized over and Fe (96 %) and Co (95 %). However, the yield of the CNTs from all three metal impregnated coal ash based catalysts was found to have decreased with increase in reaction temperature. The thermal stability of CNTs obtained over different catalysts followed the order of Fe (570 °C) > Ni (550 °C) > Co (530 °C). Further, the Raman analysis demonstrated that the produced CNTs over different catalysts showed increasing degree of graphitization with the rise in reaction temperature. Additionally, the I D /I G ratios indicated that CNTs produced from Fe catalyst showed highest degree of graphitization followed by Co and Ni. FESEM and HRTEM analysis showed that the coal ash based catalysts produced multiwalled CNTs and the diameter of the CNTs was increasing with the rise in catalysis temperature. Therefore, co-utilization of coal ash and waste plastic for production of high value CNTs can be a sustainable approach to waste management while actively contributing in circular economy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the current work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Importance: One of the most feared and devastating complications of carotid revascularization procedures is hyperperfusion hemorrhage. The acute onset of an ipsilateral mydriatic pupil following carotid endarterectomy (CEA) or carotid artery stenting (CAS) should prompt immediate neurosurgical evaluation to rule out hyperperfusion injury., Clinical Presentation: We describe a case of benign, transient ipsilateral mydriasis following CAS. After undergoing right common and internal carotid artery (ICA) angioplasty and stenting with distal embolic protection, the patient developed anisocoria with a right-sided 5 mm minimally reactive pupil. Imaging demonstrated no acute pathology, and the mydriasis resolved spontaneously within 48 hours. We hypothesise that the pathophysiologic mechanism is secondary to transient ischemia of parasympathetic structures within the petrous/cavernous ICA from arterial ostium occlusion that occurred during device placement. Alternatively, sympathetic stimulation during angioplasty is also plausible., Conclusions: Although an ipsilateral mydriatic pupil following carotid revascularization necessitates evaluation, it may represent a self-limiting process especially in the absence of other focal neurologic deficits.

Metastasis is a key determinant in cancer mortality which is often associated with decreased levels of Nm23-H1, a well-established metastasis suppressor. Despite lacking a secretion signal peptide, Nm23-H1 has been reported to be present in the extracellular space and enclosed within extracellular vesicles (EVs). While the presence of Nm23-H1 proteins in EVs released by cancer cells has been observed through proteomics profiling, the role of vesicular Nm23-H1 remains unclear. Here, we investigated the function of vesicular Nm23-H1 using MDA-MB-231 (highly metastatic, low Nm23-H1) and MCF-7 (low/non-metastatic, high Nm23-H1) breast cancer cell models. Our findings confirm that Nm23-H1 is indeed encapsulated within EVs, and its levels can be manipulated through overexpression and knockdown approaches. Functional assays revealed that EVs derived from MDA-MB-231 cells that contained high levels of Nm23-H1 exhibit impaired pro-migratory properties, suggesting that vesicular Nm23-H1 may act as a metastasis suppressor. Furthermore, EVs with increased levels of Nm23-H1 altered the transcript levels of multiple cancer-related genes in recipient cells and stimulated type I interferon signaling through STAT1 phosphorylation. These results suggest the existence of an unconventional signaling pathway mediated by the uptake of EVs enriched with Nm23-H1, which may contribute to the anti-metastatic effect of Nm23-H1 in the tumor microenvironment. Additionally, our study demonstrates that elevated Nm23-H1 levels can impact the abundance of various other proteins encapsulated within breast cancer cell-derived EVs, such as SUSD2 (Sushi Domain Containing 2) which can also modulate metastasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Scrub typhus is caused by Orientia tsutsugamushi , a Gram-negative coccobacillus. It comprises three strains: Karp, Gilliam, and Kato. Cases of scrub typhus are usually found in the Asia-Pacific region, and their presentation may range from minimal symptoms to multi-organ involvement, with or without the presence of an eschar mark. Varying manifestations of scrub typhus, such as gangrene, meningoencephalitis, anemia with jaundice, and hematuria, have been observed. In the Kumaun region of northern India, there has been a surge in the number of scrub typhus cases. Typically, this disease is accompanied by an eschar mark, but occasionally it can manifest without one. We report a series of four cases presenting with various unusual symptoms such as gangrene of the limbs, meningoencephalitis, jaundice, and hematuria. Serology for scrub typhus should be considered in all patients with acute febrile illness not responding to treatment, especially in mountainous regions, to prevent the associated mortality., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Saini et al.)

The paper "Using Absorption Models for Insulin and Carbohydrates and Deep Leaning to Improve Glucose Level Predictions" ( Sensors 2021 , 21 , 5273) proposes a novel approach to predicting blood glucose levels for people with type 1 diabetes mellitus (T1DM). By building exponential models from raw carbohydrate and insulin data to simulate the absorption in the body, the authors reported a reduction in their model's root-mean-square error (RMSE) from 15.5 mg/dL (raw) to 9.2 mg/dL (exponential) when predicting blood glucose levels one hour into the future. In this comment, we demonstrate that the experimental techniques used in that paper are flawed, which invalidates its results and conclusions. Specifically, after reviewing the authors' code, we found that the model validation scheme was malformed, namely, the training and test data from the same time intervals were mixed. This means that the reported RMSE numbers in the referenced paper did not accurately measure the predictive capabilities of the approaches that were presented. We repaired the measurement technique by appropriately isolating the training and test data, and we discovered that their models actually performed dramatically worse than was reported in the paper. In fact, the models presented in the that paper do not appear to perform any better than a naive model that predicts future glucose levels to be the same as the current ones.

Goldenhar syndrome, also known as oculo-auriculo-vertebral syndrome, is a rare congenital disorder characterized by craniofacial anomalies, ear malformations, and ocular abnormalities. It is also associated with multiple system involvement, including the central nervous system, renal, cardiovascular, and gastrointestinal systems. This case report presents a detailed description of a preterm female neonate diagnosed with Goldenhar syndrome. Many of the classical features, along with ventricular septal defect (VSD), were present in our patient. She was complicated by prematurity and a urinary tract infection and was later diagnosed with a VSD at the age of three months. The multidisciplinary examination and management involving pediatricians, pediatric surgeons, ophthalmologists, and otorhinolaryngologists led to comprehensive care for the patient. This case emphasizes the importance of early diagnosis and management for optimal patient outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Saini et al.)

Background: Acute ischemic stroke with isolated posterior cerebral artery occlusion (iPCAO) lacks management evidence from randomized trials. We aimed to evaluate whether the association between endovascular treatment (EVT) and outcomes in iPCAO acute ischemic stroke is modified by initial stroke severity (baseline National Institutes of Health Stroke Scale [NIHSS]) and arterial occlusion site., Methods: Based on the multicenter, retrospective, case-control study of consecutive iPCAO acute ischemic stroke patients (PLATO study [Posterior Cerebral Artery Occlusion Stroke]), we assessed the heterogeneity of EVT outcomes compared with medical management (MM) for iPCAO, according to baseline NIHSS score (≤6 versus >6) and occlusion site (P1 versus P2), using multivariable regression modeling with interaction terms. The primary outcome was the favorable shift of 3-month modified Rankin Scale (mRS). Secondary outcomes included excellent outcome (mRS score 0-1), functional independence (mRS score 0-2), symptomatic intracranial hemorrhage, and mortality., Results: From 1344 patients assessed for eligibility, 1059 were included (median age, 74 years; 43.7% women; 41.3% had intravenous thrombolysis): 364 receiving EVT and 695 receiving MM. Baseline stroke severity did not modify the association of EVT with 3-month mRS distribution ( P interaction =0.312) but did with functional independence ( P interaction =0.010), with a similar trend on excellent outcome ( P interaction =0.069). EVT was associated with more favorable outcomes than MM in patients with baseline NIHSS score >6 (mRS score 0-1, 30.6% versus 17.7%; adjusted odds ratio [aOR], 2.01 [95% CI, 1.22-3.31]; mRS score 0 to 2, 46.1% versus 31.9%; aOR, 1.64 [95% CI, 1.08-2.51]) but not in those with NIHSS score ≤6 (mRS score 0-1, 43.8% versus 46.3%; aOR, 0.90 [95% CI, 0.49-1.64]; mRS score 0-2, 65.3% versus 74.3%; aOR, 0.55 [95% CI, 0.30-1.0]). EVT was associated with more symptomatic intracranial hemorrhage regardless of baseline NIHSS score ( P interaction =0.467), while the mortality increase was more pronounced in patients with NIHSS score ≤6 ( P interaction =0.044; NIHSS score ≤6: aOR, 7.95 [95% CI, 3.11-20.28]; NIHSS score >6: aOR, 1.98 [95% CI, 1.08-3.65]). Arterial occlusion site did not modify the association of EVT with outcomes compared with MM., Conclusions: Baseline clinical stroke severity, rather than the occlusion site, may be an important modifier of the association between EVT and outcomes in iPCAO. Only severely affected patients with iPCAO (NIHSS score >6) had more favorable disability outcomes with EVT than MM, despite increased mortality and symptomatic intracranial hemorrhage., Competing Interests: Disclosures Dr Dabus: consultancy for Cerenovus, Penumbra, Route 92, Medtronic, MicroVention, and Stryker; stock holdings in RIST and InNeuroCo. Dr Fifi: consultancy for Cerenovus, MicroVention, and Stryker; Data Safety Monitoring Board (DSMB) for MIVI; stock holdings in Imperative Care and Sim&Cure. Dr Fischer: research support from the Swiss National Science Foundation (SNF), Medtronic, Stryker, Rapid Medical, Penumbra, and Phenox; consultancies for Stryker and CSL Behring; is on the advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera. Dr Haussen: consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; DSMB for Jacobs Institute; stock options in viz AI. Dr Herweh: consultancy for Brainomix; speaker with Stryker. Dr Jadhav: consulting with Basking Biosciences; stock options in Gravity Medical Technology; a patent for a novel stent retriever device licensed to Basking Biosciences; and Editor-in-Chief for the Stroke: Vascular and Interventional Neurology journal. Dr Kaesmacher: grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Kaiser: grants from the Joachim Herz Foundation. Dr Kuramatsu: grants from Alexion Pharmaceuticals, Bayer Healthcare, Sanofi Pasteur, and Biogen Idec. Dr Marto: consulting and speaker fees from Amicus Therapeutics and Boehringer Ingelheim. Dr Michel: grants from the University of Lausanne and SNF. Dr Möhlenbruch: grants from Medtronic, Stryker, and MicroVention. Dr Mokin: stock holdings in BrainQ, Serenity Medical, Synchron, and Bendit Technology; consulting at MicroVention, Medtronic, and Johnson & Johnson. Dr Nagel: consultancy for Brainomix; speaker at Boehringer Ingelheim and Pfizer. Dr Nguyen: Associate Editor of Stroke, advisory board at Aruna Bio and Brainomix. Dr Nogueira: consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, and RapidPulse; stock options in viz AI, Vesalio, Perfuze, Corindus, Brainomix, and Ceretrieve; grants from Cerenovus and Stryker. Dr Nolte: research support and compensation from Novartis, AstraZeneca, Deutsches Zentrum für Herz-Kreislaufforschung, and Deutsches Zentrum für Neurodegenerative Erkrankungen; consultancy for Alexion, Daiichi Sankyo, Novartis, AstraZeneca, Bayer Healthcare, Pfizer, Alexion, and Bristol Myers Squibb. S. Poli: research grants from BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, German Federal Joint Committee Innovation Fund, and German Federal Ministry of Education and Research, Helena Laboratories and Werfen as well as speakers’ honoraria/consulting fees from Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Werfen (all outside of the submitted work). Dr Psychogios: grants from Penumbra, Rapid Medical, Medtronic, Phenox, Bangerter-Rhyner Stiftung, SNF, Siemens Healthineers, and Stryker Neurovascular; travel support from Medtronic, Siemens Healthineers, Phenox, Penumbra, and Stryker; consultancy for Siemens Healthineers. Dr Puetz: lecturer for Daiichi Sankyo. Dr Ribo: consultancy for Medtronic MiniMed, Cerenovus, AptaTargets, Stryker, and Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Ringleb: travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Romoli: research grants from the Italian Stroke Association; consultancy for CSL Behring. Dr Sheth: consultancy for Imperative Care, viz AI, and Penumbra; compensation from Motif Neurosciences (other services); grants from the National Institutes of Health. Dr Siddiqui: ownership stake in Integra Lifesciences and Medtronic; consultancy for Cordis, Rapid Medical, MicroVention, Medtronic Vascular, Vassol, IRRAS USA, Boston Scientific, Amnis Therapeutics, Minnetronix Neuro, Canon Medical Systems USA, Cardinal Health 200, Johnson & Johnson–Latin America, Corindus, Penumbra, Apellis Pharmaceuticals, W.L. Gore & Associates, Stryker Corporation, and viz AI; stock holdings in E8, Spinnaker Medical, Endostream Medical, Cerebrotech Medical Systems, Adona Medical, Bend IT Technologies, Whisper Medical, Neurotechnology Investors, Collavidence, Instylla, Q’Appel Medical, Serenity Medical, Borvo Medical, NeuroRadial Technologies, Sense Diagnostics, Tulavi Therapeutics, Synchron, Neurolutions, Viseon, BlinkTBI, Radical Catheter Technologies, and Truvic Medical; stock options in viz AI, StimMed, Three Rivers Medical, Silk Road Medical, Imperative Care, CVAid Ltd, Cerevatech Medical, InspireMD, PerFlow Medical; security holdings in Vastrax, Launch NY, QAS.ai, VICIS, Inc, Neurovascular Diagnostics, Cognition Medical, and SongBird Therapy. Dr Strbian: Assistant Editor of Stroke, Editorial Board of European Stroke Journal, advisory board at Boehringer Ingelheim, Alexion/AstraZeneca, and Bristol Myers Squibb/Janssen; research support from Boehringer Ingelheim; consultancies for Orion, Herantis Pharma, and CSL Behring. The other authors report no conflicts.

Background: Defensins are key effector molecules of innate immunity that can contribute towards the diagnosis and monitoring of chronic obstructive pulmonary disease (COPD). The present study was conducted to investigate the role of alpha-defensins in patients with COPD by quantifying serum and sputum samples., Methods: A total of 180 patients were enrolled and divided into four groups, and sputum and serum values of alpha-defensins were assessed. The sensitivity, specificity, and accuracy of sputum alpha-defensin as a diagnostic biomarker were evaluated to assess its utility in diagnosing COPD., Results: The mean value of sputum alpha-defensins was found to be statistically significant amongst the four groups (P < 0.001). The highest levels were found in subjects with AECOPD (385.76 ± 116.62 ng/mL). Sputum alpha-defensins were found to be negatively correlated with FEV 1 values (rho = -0.31, P < 0.001)., Conclusion: Sputum alpha-defensins can be used as a potential marker for predicting acute exacerbation of COPD. In addition, they could serve as an indicator of disease severity in COPD patients., (Copyright © 2024 Copyright: © 2024 Indian Chest Society.)

Large ventral hernias require complex surgical techniques, such as component separation. We are presenting a case of an incisional hernia measuring 15×8 cm. The hernia was covered with an overlying thin layer of skin and hernia sac. The skin of this layer was densely adherent to the underlying hernial sac. Because of the thin hernial sac and adherent nature of the skin, approximately 3 cm of the hernial sac was preserved. We used this hernial sac as the anterior sheath 'extension' for a tension-free closure. Posterior component separation with transverse abdominis muscle release was done to close the posterior layer without tension and to place a 23×16 cm mesh in the retrorectus plane. By using the hernial sac in repair, we avoided anterior component separation and achieved tension-free closure of the anterior layer., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Ascariasis infection is prevalent in tropical and subtropical locations worldwide. The occurrence of ascariasis is associated with poverty, inadequate hygiene, and inadequate fecal sanitation. This helminth often resides innocuously in the small intestine, but it may sometimes lead to intestinal blockage or perforation, resulting in peritonitis, a condition frequently seen in children. Ascariasis may also migrate via the ampulla of Vater, leading to the development of cholangitis, pancreatitis, cholecystitis, and, in rare cases, hepatic abscesses. Occasionally, an Ascaris-induced hepatic abscess may manifest as an acute abdomen, resembling an acute pyogenic abscess. We report the case of a four-and-a-half-year-old male child from Khedi Sikarpur, Haridwar, India, who was admitted to the pediatric department. The patient presented with acute colicky abdominal pain localized to the abdomen, accompanied by vomiting and constipation for three days. Additionally, the patient experienced abdominal distension for one day. There was no history of bleeding manifestations or decreased urine output., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Saini et al.)

Background: Maternal depression and anxiety can have a detrimental impact on birth outcomes and healthy child development; there is limited knowledge on its influence on immunization schedule adherence. Therefore, the objectives of this study were to determine the impact of maternal depression and anxiety in the perinatal period on prolonged vaccine delay of childhood vaccines., Methods: In this prospective cohort study, we analyzed linked survey and administrative data of 2,762 pregnant women in Calgary, Alberta, Canada. Data were collected at two time-points: prenatal (< 25 weeks of gestation) and postpartum (4 months postpartum). We used multivariable logistic regression to examine the association between depression and anxiety with prolonged immunization delay, adjusting for covariates., Results: In multivariable analysis, maternal depression at either time point was not associated with prolonged delay for DTaP-IPV-Hib (OR 1.16, 95% CI 0.74-1.82), MMR/MMRV (OR 1.03, 95% CI 0.72-1.48), or all routine childhood vaccines combined (OR 1.32, 95% CI 0.86-2.04). Maternal anxiety at either time point was also not associated with prolonged delayed for DTaP-IPV-Hib (OR 1.08, 95% CI 0.77-1.53), MMR/MMRV (OR 1.07, 95% CI 0.82-1.40), or all vaccines combined (OR 1.00, 95% CI 0.80-1.26). In both the depression and anxiety models, children of Canadian-born mothers had higher odds of prolonged delay, as did those with low-income mothers., Conclusion: Health care providers can be reassured that maternal depression and anxiety do not appear to influence maternal commitment to routine immunization. Findings suggested that low income and household moves may influence adherence to vaccine schedules and health care providers may want to provide anticipatory guidance to these families., (© 2024. The Author(s).)

Pretomanid (PTM), an oral antibiotic used in the treatment of adults with pulmonary extensively drug-resistant, nonresponsive multidrug-resistant tuberculosis (MDR-TB). It is a poor glass former, that shows high recrystallization tendency from the amorphous and supersaturated state, resulting in low aqueous solubility and suboptimal absorption through the gastrointestinal tract. The present investigation aimed to develop high drug loaded ternary amorphous solid dispersions (ASDs) of PTM with improved stability and enhanced biopharmaceutical performance by utilizing a combination of polymers. The polymers were comprehensively screened based on drug-polymer miscibility and saturation solubility analysis. A combination of Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS-HF) and Polyvinylpyrrolidone K-30 (PVP K-30) showed synergism in drug-polymer miscibility as evidenced through pronounced depression in the melting endotherm of PTM. The Powder X-ray Diffraction (P-XRD) diffractograms of 30% w/w PTM loaded ternary ASDs displayed the halo pattern, contrary to the binary ASDs. Drug-polymer interactions (hydrophobic forces) involved between PTM and polymers were detected through Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance Spectroscopy ( 13 C-NMR) which contributed to the synergistic enhancement in solubility and dissolution of ternary ASDs with sustained release over 12 h. Ternary ASDs demonstrated better in-vivo performance compared to the binary ASDs, showing a 4.63-fold increase in maximum plasma concentration. All ASDs remained stable and resisted phase separation during short-term stability studies for 3 months at ambient conditions. It was concluded that the hydrophobic and hydrophilic polymeric combination (HPMCAS-HF and PVP K-30, respectively) effectively prevented the crystallization and ensured sustained drug release with improved in-vivo absorption of PTM., (© 2024. Controlled Release Society.)

The leaves of Araucaria cunninghamii are known to be nonedible and toxic. Previous studies have identified biflavones in various Araucaria species. This study aimed to investigate the in vitro cytotoxicity of the isolated compounds from Araucaria cunninghamii after metabolomics and network pharmacological analysis. Methanol extract of Araucaria cunninghamii leaves was subjected to bioassay-guided fractionation. The active fraction was analyzed using LC-HRMS, through strategic database mining, by comparing the data to the Dictionary of Natural Products to identify 12 biflavones, along with abietic acid, beta-sitosterol, and phthalate. Eight compounds were screened for network pharmacology study, where in silico ADME analysis, prediction of gene targets, compound-gene-pathway network and hierarchical network analysis, protein-protein interaction, KEGG pathway, and Gene Ontology analyses were done, that showed PI3KR1, EGFR, GSK3B, and ABCB1 as the common targets for all the compounds that may act in the gastric cancer pathway. Simultaneously, four biflavones were isolated via chromatography and identified through NMR as dimeric apigenin with varying methoxy substitutions. Cytotoxicity study against the AGS cell line for gastric cancer showed that AC1 biflavone (IC 50 90.58 μM) exhibits the highest cytotoxicity and monomeric apigenin (IC 50 174.5 μM) the lowest. Besides, the biflavones were docked to the previously identified targets to analyze their binding affinities, and all the ligands were found to bind with energy ≤-7 Kcal/mol., (© 2024 John Wiley & Sons Ltd.)

Introduction: The purpose of this study was to report our initial experience of using a large-bore (0.096″ inner diameter) access catheter in neurovascular interventions., Methods: Data were retrospectively collected from 5 sites in the US for neurovascular procedures performed using a large-bore access catheter. The effectiveness outcome was technical success, defined as the access catheter's successfully reaching its target vessel without conversion to direct carotid puncture or to a smaller-bore access catheter and successfully completing the intended neurointervention., Results: One hundred and thirteen procedures performed in 112 patients were included in this study. The mean age of the patients was 67.5 years (SD 16.2), and about half (49.1%) were female. The most common primary access sites were the femoral (64.6%) or radial (32.7%) artery. Challenging anatomic variations included severe vessel tortuosity (26/81, 32.1%), type II aortic arch (17/88, 19.3%), type III aortic arch (14/88, 15.9%), bovine arch (16/104, 15.4%), severe angle (<30°) between the subclavian and target vessel (11/74, 14.9%), and subclavian loop (7/79, 8.9%). The median access time to branch view was 18 min (IQR 11-28, N = 75). The technical success rate was 94.7%. Two dissections (1.8%) were related to the large-bore access catheter. Access site complications occurred in 2 patients (1.8%). Four additional symptomatic periprocedural complications not related to the large-bore access catheter occurred (7.1%)., Conclusion: For neurovascular interventions, a 0.096″ inner diameter access catheter could be used with both femoral and radial arterial approaches, had a high technical success rate, and had a low rate of periprocedural complications., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Robert M Starke: Research supported by the NREF, Joe Niekro Foundation, Brain Aneurysm Foundation, Bee Foundation, and by National Institute of Health (R01NS111119-01A1) and (UL1TR002736, KL2TR002737) through the Miami Clinical and Translational Science Institute, from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Unrestricted research grant from Medtronic. Consulting and teaching agreements with Penumbra, Abbott, Medtronic, Balt, InNeuroCo, Cerenovus, Naglreiter, and Optimize Vascular. Isaac Josh Abecassis: Consulting agreements with IschemaView (Rapid) and Remedy Robotics. Equity with Remedy Robotics. Vasu Saini: Nothing to disclose. Charles C Matouk: Consultant for Penumbra, Stryker, Microvention-Terumo, and Silk Road Medical. Paid speaker for Penumbra and Silk Road Medical. Ameer E Hassan: Consultant/Speaker for Medtronic, Microvention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera Therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, Rapid Medical, Imperative Care and Galaxy Therapeutics. Principal Investigator for COMPLETE study (Penumbra) and LVO SYNCHRONISE (Viz.ai). Steering Committee/Publication committee member for SELECT, DAWN, SELECT 2, EXPEDITE II, EMBOLISE, CLEAR, ENVI, and DELPHI. Data and Safety Monitoring Board for COMAND trial Adnan H Siddiqui: Current Research Grants: Co-investigator for NIH - 1R01EB030092-01, Project Title: High Speed Angiography at 1000 frames per second; Mentor for Brain Aneurysm Foundation Carol W. Harvey Chair of Research, Sharon Epperson Chair of Research, Project Title: A Whole Blood RNA Diagnostic for Unruptured Brain Aneurysm: Risk Assessment Prototype Development and Testing. Financial Interest/Investor/Stock Options/Ownership: Adona Medical, Inc., Amnis Therapeutics, Bend IT Technologies, Ltd., BlinkTBI, Inc, Cerebrotech Medical Systems, Inc., Cerevatech Medical, Inc., Cognition Medical, CVAID Ltd., E8, Inc., Endostream Medical, Ltd, Galaxy Therapeutics, Inc., Imperative Care, Inc., InspireMD, Ltd., Instylla, Inc., International Medical Distribution Partners, Launch NY, Inc., Neurolutions, Inc., NeuroRadial Technologies, Inc., NeuroTechnology Investors, Neurovascular Diagnostics, Inc., Peijia Medical, PerFlow Medical, Ltd., Q'Apel Medical, Inc., QAS.ai, Inc., Radical Catheter Technologies, Inc., Rebound Therapeutics Corp. (Purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc. (Purchased 2020 by Medtronic), Sense Diagnostics, Inc., Serenity Medical, Inc., Silk Road Medical, Sim & Cure, SongBird Therapy, Spinnaker Medical, Inc., StimMed, LLC, Synchron, Inc., Three Rivers Medical, Inc., Truvic Medical, Inc., Tulavi Therapeutics, Inc., Vastrax, LLC, VICIS, Inc., Viseon, Inc. Consultant/Advisory Board: Amnis Therapeutics, Apellis Pharmaceuticals, Inc., Boston Scientific, Canon Medical Systems USA, Inc., Cardinal Health 200, LLC, Cerebrotech Medical Systems, Inc., Cerenovus, Cerevatech Medical, Inc., Cordis, Corindus, Inc., Endostream Medical, Ltd, Imperative Care, InspireMD, Ltd., Integra, IRRAS AB, Medtronic, MicroVention, Minnetronix Neuro, Inc., Peijia Medical, Penumbra, Q'Apel Medical, Inc., Rapid Medical, Serenity Medical, Inc., Silk Road Medical, StimMed, LLC, Stryker Neurovascular, Three Rivers Medical, Inc., VasSol, Viz.ai, Inc. National PI/Steering Committees: Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial & CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial, MIVI neuroscience EVAQ Trial; Rapid Medical SUCCESS Trial; InspireMD C-GUARDIANS IDE Pivotal Trial. Donald F Frei: Consultant and speakers bureau for Penumbra.

Intervention: Alberta Health Services (AHS) Community Helpers Program (CHP) to enhance mental health among youth., Research Question: Identifying the impact of CHP on mental illness-related acute care use among adolescents aged 12-18 years in Edmonton and determining cost avoidance., Methods: Using administrative data from AHS, public school catchment area data from the Edmonton Public School Board, and area-level socioeconomic deprivation status indicators from the Pampalon deprivation index, we applied geographical regression discontinuity design to estimate the effect of CHP implementation on depression-, anxiety-, and suicide-related acute care use (emergency department visits and inpatient admissions). Cost data were derived from Interactive Health Data Application of Alberta Health. The study period (2002-2022) included pre (2002-2011) and post (2012-2020) CHP implementation periods., Results: CHP had statistically significant impact when distance from the boundary (catchment area identifier to divide the sample into treated and control groups) was between 600 and 800 m. About 90 and 80 fewer anxiety- and depression-related visits (per 1000 visits) were observed among individuals aged 12-15 and 16-18 years, respectively, in catchment areas of the public schools where CHP was implemented. Impact of CHP on suicide-related visits was only statistically significant among individuals aged 12-15 years. Annual cost reduction ranged from $161,117 to $269,255 for anxiety- and depression-related visits., Conclusion: Findings show contextual effect of CHP; i.e., being potentially exposed to the program reduced the likelihood of anxiety- and depression-related visits. Costs of CHP implementation could be compared with the avoided costs to assess economic benefits of implementing CHP., (© 2024. The Author(s) under exclusive license to The Canadian Public Health Association.)

Cold stratification is known to affect the speed of seed germination; however, its regulation at the molecular level in Ferula assa-foetida remains ambiguous. Here, we used cold stratification (4 °C in the dark) to induce germination in F. assa-foetida and adopted a proteomic and metabolomic approach to understand the molecular mechanism of germination. Compared to the control, we identified 209 non-redundant proteins and 96 metabolites in germinated F. assa-foetida seed. Results highlight the common and unique regulatory mechanisms like signaling cascade, reactivation of energy metabolism, activation of ROS scavenging system, DNA repair, gene expression cascade, cytoskeleton, and cell wall modulation in F. assa-foetida germination. A protein-protein interaction network identifies 18 hub protein species central to the interactome and could be a key player in F. assa-foetida germination. Further, the predominant metabolic pathways like glucosinolate biosynthesis, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, and carotenoid biosynthesis in germinating seed may indicate the regulation of carbon and nitrogen metabolism is prime essential to maintain the physiology of germinating seedlings. The findings of this study provide a better understanding of cold stratification-induced seed germination, which might be utilized for genetic modification and traditional breeding of Ferula assa-foetida. SIGNIFICANCE: Seed germination is the fundamental checkpoint for plant growth and development, which has ecological significance. Ferula assa-foetida L., commonly known as "asafoetida," is a medicinal and food crop with huge therapeutic potential. To date, our understanding of F. assa-foetida seed germination is rudimentary. Therefore, studying the molecular mechanism that governs dormancy decay and the onset of germination in F. assa-foetida is essential for understanding the basic principle of seed germination, which could offer to improve genetic modification and traditional breeding., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Mycobacterium tuberculosis (MTB) is the causative organism of tuberculosis. Cholesterol is a crucial carbon source required for the survival of MTB in host cells. Transcription factor NR1H3 along with its important target genes ABCA1 and ApoE play important role in removal of extra cholesterol from cells. Changes in the gene expression of NR1H3, ABCA1 and ApoE can affect cholesterol homeostasis and thus the survival of MTB in host cells.Therefore, the present study was designed to analyze the mRNA expression of NR1H3, ABCA1 and ApoE in pulmonary TB (PTB) patients from the population of Punjab, India., Methods and Results: In this study, mRNA expression of the transcription factor NR1H3 and its target genes ABCA1 and ApoE was analyzed in 89 subjects, including 41 PTB patients and 48 healthy controls (HCs) by real-time quantitative PCR. It was found that the mRNA expression of both NR1H3 and ABCA1 genes was significantly lower in TB patients than in HCs (p < 0.001). Even after sex-wise stratification of the subjects, mRNA expression of NR1H3 and ABCA1 was found to be down-regulated in both male and female TB patients. No significant difference was observed in expression of ApoE (p = 0.98)., Conclusions: The present study found that the mRNA expression of NR1H3 and ABCA1 is down-regulated in TB patients from Punjab state of India., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Purpose: Posterior cerebral artery occlusion (PCAo) can cause long-term disability, yet randomized controlled trials to guide optimal reperfusion strategy are lacking. We compared the outcomes of PCAo patients treated with endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) to patients treated with IVT alone., Methods: From the multicenter retrospective Posterior cerebraL ArTery Occlusion (PLATO) registry, we included patients with isolated PCAo treated with reperfusion therapy within 24 hours of onset between January 2015 and August 2022. The primary outcome was the distribution of the modified Rankin Scale (mRS) at 3 months. Other outcomes comprised 3-month excellent (mRS 0-1) and independent outcome (mRS 0-2), early neurological improvement (ENI), mortality, and symptomatic intracranial hemorrhage (sICH). The treatments were compared using inverse probability weighted regression adjustment., Results: Among 724 patients, 400 received EVT+/-IVT and 324 IVT alone (median age 74 years, 57.7% men). The median National Institutes of Health Stroke Scale score on admission was 7, and the occluded segment was P1 (43.9%), P2 (48.3%), P3-P4 (6.1%), bilateral (1.0%), or fetal posterior cerebral artery (0.7%). Compared to IVT alone, EVT+/-IVT was not associated with improved functional outcome (adjusted common odds ratio [OR] 1.07, 95% confidence interval [CI] 0.79-1.43). EVT increased the odds for ENI (adjusted OR [aOR] 1.49, 95% CI 1.05-2.12), sICH (aOR 2.87, 95% CI 1.23-6.72), and mortality (aOR 1.77, 95% CI 1.07-2.95)., Conclusion: Despite higher odds for early improvement, EVT+/-IVT did not affect functional outcome compared to IVT alone after PCAo. This may be driven by the increased risk of sICH and mortality after EVT.

Background: Postoperative delirium is a common complication in patients undergoing elective surgery under general anesthesia. We aimed to minimize the incidence with an oral dose of 3 mg of melatonin administered the night before surgery., Methods: Hundred and sixty-two patients aged 40-80 years posted for various urological and gastrointestinal surgeries under general anesthesia with no preoperative cognitive deficits were randomly distributed equally to melatonin or control groups. In the control group, routine premedication was done with tablet alprazolam (0.25 mg) and ranitidine (150 mg), but in the melatonin group, the patients were given 3 mg melatonin orally the night before surgery along with routine premedication. The CAM scale was used for diagnosis of postoperative delirium., Results: Incidence of delirium was significantly lower in the melatonin group, 23.5%, 8.6%, and 2.5% at 6, 24, and 48 hours, respectively, and the corresponding mean (SD) values of CAM scores were 1.37 (1.30), 1.07 (1.03), and 0.69 (0.80). In contrast, the incidence of delirium was 46.9%, 30.9%, and 16% at 6, 24, and 48 hours, respectively, in the control group. There was a significant reduction in anxiety, a lower incidence of cognitive dysfunction (i.e., MoCA score <26), and improvement in sleep quality in the melatonin group at 6, 24, 48, and 72 hours after the surgical intervention. The generalized estimating equations model (GEE) model was used to study change in MoCA and CAM scores over time between the two groups, and it showed a significant interaction between time and treatment groups ( P < 0.001)., Conclusions: Melatonin premedication reduced incidence of postoperative delirium and cognitive dysfunction and was associated with better sleep quality and anxiolysis., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Psychiatry.)

Background and Aim: Sevoflurane, a preferred anaesthetic for children, exhibits a dose-dependent reduction in intraocular pressure (IOP). However, consensus is lacking regarding optimal end-tidal sevoflurane concentration for safe IOP measurement. This study aimed to identify the concentration at which IOP measurement could be attempted without inducing movements in paediatric patients after inhalational induction., Methods: Two paediatric groups (1-12 months and 12-36 months) with glaucoma undergoing examination under anaesthesia were recruited. After induction with 8% sevoflurane and 100% oxygen, the first child had an end-tidal sevoflurane concentration maintained at 2% for 4 min, followed by IOP measurement. Success was defined as 'no movement', and subsequent concentrations (adjusted in 0.2% steps) were determined using the Dixon and Massey method based on the previous patient's responses., Results: The study included 75 children. The effective concentration of sevoflurane causing 'no movement' during IOP measurement in 50% of the study population for successful IOP measurement was 1.98% (95% confidence interval [CI] 1.63, 2.17, P = 0.017) for 1-12 months group and 0.55% (95% CI 0.39, 0.66, P = 0.002) for 12-36 months group. Probit regression analysis yielded effective concentration of sevoflurane causing 'no movement' during IOP measurement in 95% of the study population values of 2.47% (95% CI 2.24, 4.58, P = 0.017) for 1-12 months group and 0.94% (95% CI 0.78, 1.57, P = 0.002) for 12-36 months group., Conclusion: In paediatric patients, a higher end-tidal sevoflurane concentration of 2% is needed for IOP measurement in 1-12 months age group compared to 0.5% required in 12-36 months age group, achieving success in 50% of the study population., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Anaesthesia.)

Objective: To determine whether enteral melatonin decreases the incidence of delirium in critically ill adults., Methods: In this randomized controlled trial, adults were admitted to the intensive care unit and received either usual standard care alone (Control Group) or in combination with 3mg of enteral melatonin once a day at 9 PM (Melatonin Group). Concealment of allocation was done by serially numbered opaque sealed envelopes. The intensivist assessing delirium and the investigator performing the data analysis were blinded to the group allocation. The primary outcome was the incidence of delirium within 24 hours of the intensive care unit stay. The secondary outcomes were the incidence of delirium on Days 3 and 7, intensive care unit mortality, length of intensive care unit stay, duration of mechanical ventilation and Glasgow outcome score (at discharge)., Results: We included 108 patients in the final analysis, with 54 patients in each group. At 24 hours of intensive care unit stay, there was no difference in the incidence of delirium between Melatonin and Control Groups (29.6 versus 46.2%; RR = 0.6; 95%CI 0.38 - 1.05; p = 0.11). No secondary outcome showed a statistically significant difference., Conclusion: Enteral melatonin 3mg is not more effective at decreasing the incidence of delirium than standard care is in critically ill adults.

Corona mortis (CM) is an anastomotic vessel between the inferior epigastric or external iliac vessels and the obturator or internal iliac vessels. The Latin meaning of it is 'crown of death' which corresponds to massive haemorrhage caused by injury to this vessel during surgery. The incidence of this vessel is around 50% in the hemipelvis. We are presenting an intraoperative video of a right laparoscopic totally extraperitoneal mesh hernioplasty demonstrating a CM artery in the right hemipelvis. Care was taken to prevent injury to this vessel. CO 2 insufflation pressure was reduced to less than 10 mm Hg to see any venous variant of this vessel. Carefully, polypropylene mesh was placed without a fixation device. Anatomical knowledge of the CM vessel is therefore essential in preventing injury for surgeons who approach the inguinal and retropubic regions., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Epileptic seizures are directly linked with an anomalous influx of extracellular calcium or sodium anions through voltage-gated channels disturb the chemical and electrical gradients, resulting in seizures or jerking moments. Voltage-gated calcium channel (VGCC) subunit α2δ-1 is the binding site for gabapentinoids used to treat epilepsy and neuropathic pain. However, this class of drugs showed severe side effects associated with CNS and respiratory depression. Hence, we screened a total of 2583 phytochemicals from the Comprehensive Marine Natural Products Database for their drug likeliness and pharmacokinetics (ADME/T) properties. The selected phytochemicals were docked with the VGCC α2δ-1 protein target and the marketed AED Pregabalin is used as standard. The docking results helped to select 45 docked compounds with better binding affinity, among which Acanthiline A showed the maximum binding affinity with the binding energy of -11.9 kcal/mol, thus reflecting its potential anti-epileptic activity., Competing Interests: The authors declare no conflict of interest., (© 2024 Biomedical Informatics.)

α-Synuclein aggregation into toxic oligomeric species is central to Parkinson's disease pathogenesis. Anle138b is a recently identified inhibitor of α-synuclein oligomerization showing promise in preclinical studies. This study employed computational approaches to elucidate Anle138b's mechanism of oligomer-specific action. The inhibitory potential of Anle138b against α-synuclein oligomers was evaluated by performing molecular docking studies using AutoDock Tools, followed by their binding pocket analysis. Further, protein-protein docking studies were performed using Hex8.0 to validate the aggregation inhibitory potential of Anle138b. Molecular docking revealed increasing binding affinity of Anle138b against higher order α-synuclein oligomers (dimer to decamer). Anle138b occupied oligomeric cavity and interacted with residues Thr54, Gly73, Val74 and Thr75 across several oligomers. Protein-protein docking showed that Anle138b interferes with α-synuclein decamer formation. These results highlight the oligomer-directed inhibitory mechanism of Anle138b, without hindering the monomeric forms and provide molecular insights to advance its therapeutic development for Parkinson's and related synucleinopathies., Competing Interests: The authors declare no conflict of interest., (© 2024 Biomedical Informatics.)

Multi-walled Carbon Nanotubes (MWCNTs) are inert structures with high aspect ratios that are widely used as vehicles for targeted drug delivery in cancer and many other diseases. They are largely non-toxic in nature however, when cells are exposed to these nanotubes for prolonged durations or at high concentrations, they show certain adverse effects. These include cytotoxicity, inflammation, generation of oxidative stress, and genotoxicity among others. To combat such adverse effects, various moieties can be attached to the surface of these nanotubes. Curcumin is a known anti-inflammatory, antioxidant and cytoprotective compound derived from a medicinal plant called Curcuma longa. In this study, we have synthesized and characterized Curcumin coated-lysine functionalized MWCNTs and further evaluated the cytoprotective, anti-inflammatory, antioxidant and antiapoptotic effect of Curcumin coating on the surface of MWCNTs. The results show a significant decrease in the level of inflammatory molecules like IL-6, IL-8, IL-1β, TNFα and NFκB in cells exposed to Curcumin-coated MWCNTs as compared to the uncoated ones at both transcript and protein levels. Further, compared to the uncoated samples, there is a reduction in ROS production and upregulation of antioxidant enzyme-Catalase in the cells treated with Curcumin-coated MWCNTs. Curcumin coating also helped in recovery of mitochondrial membrane potential in the cells exposed to MWCNTs. Lastly, cells exposed to Curcumin-coated MWCNTs showed reduced cell death as compared to the ones exposed to uncoated MWCNTs. Our findings suggest that coating of Curcumin on the surface of MWCNTs reduces its ability to cause inflammation, oxidative stress, and cell death., (© 2024. The Author(s).)

Alzheimer's disease (AD) is the leading cause of dementia worldwide with therapeutic lacunae till date. The beta-amyloid (Aβ) accumulation triggers AD pathogenesis, though clinical trials lowering Aβ have not altered disease outcomes suggesting other interacting factors to be identified for drug design of AD. Therefore, it is of interest to identify potential hub proteins interlinked with disease-driving pathways using a network-based approach for AD therapeutic designing. Literature mining was done to identify proteins implicated in AD etiology. Protein-protein interactions (PPIs) were retrieved from the STRING database and merged into a single network using Cytoscape 3.10.1. The hub proteins involved in AD etiology were predicted based on the topological algorithms of CytoHubba. Six major proteins, with STRING database identifiers - APP, BACE1, PSEN1, MAPT, APOE4 and TREM2, were identified to be involved in AD pathogenesis. The merged network of PPIs of these proteins contained 51 nodes and 211 edges, as predicted by Analyzer module of Cytoscape. The Amyloid precursor protein (APP) emerged as the highest-scoring hub protein across multiple centrality measures and topological algorithms. Thus, current data provides evidence to support the ongoing investigation of APP's multifaceted functions and therapeutic potential for AD., Competing Interests: The authors declare no conflict of interest., (© 2024 Biomedical Informatics.)

Alzheimer's disease (AD), a debilitating neurodegenerative condition, is characterized by progressive cognitive decline brought about by the deposition of amyloid beta (Aβ) plaques in the brain initiates downstream neuronal dysfunction and death in AD pathogenesis. The β-secretase (BACE-1) enzyme plays a crucial role in generating Aβ from amyloid precursor protein (APP). Hence, we report the virtual screening of marine phytochemicals as BACE-1 inhibitors. 2583 compounds, retrieved from Comprehensive Marine Natural Product Database (CMNPD), were primarily screened for drug-likeliness and blood-brain barrier permeability using admetSAR 2.0 and in-house BBBper tool and resulted in a total of 635 phytochemicals, selected for further docking studies using BACE-1 as target receptor and Atabecestat as standard BACE-1 inhibitor. Seven of 635 compounds docked against BACE-1, showed better binding affinities than Atabecestat, with the red algal metabolite lactodehydrothyrsiferol showing lowest binding energy of -10.83 kcal/mol. These compounds are worth investigating further to assess their neuroprotective efficacy and pharmacokinetic properties. The study also provides a rational framework to uncover novel pharmacophores from marine sources for AD therapy acting through BACE-1 inhibition., Competing Interests: The authors declare no conflict of interest., (© 2024 Biomedical Informatics.)

Psychological co-morbidities are common in chronic obstructive pulmonary disease (COPD) but remain overlooked. Psychosocial interventions are deemed to promote mental health and optimize management. This study aimed to determine the role of detailed psychological evaluation and treatment in the comprehensive management of COPD. COPD patients after screening with the general health questionnaire-12 (GHQ-12) for psychological co-morbidity were divided into three groups (26 patients each): i) group A [GHQ-12 score<3, received pulmonary rehabilitation (PR) and standard medical management]; ii and iii) group B and C (GHQ-12 score>3, in addition, received management by a psychiatrist and counseling by a pulmonologist, respectively). At baseline and 8 weeks of follow-up, all participants were evaluated for respiratory [forced expiratory volume in the first second (FEV1), six-minute walk distance (6-MWD), St. George's respiratory questionnaire (SGRQ), modified medical research council (mMRC) dyspnea scale], and psychological [GHQ-12, patient distress thermometer (PDT), coping strategy checklist (CSCL), World Health Organization-quality of life-brief (WHOQOL-Bref-26), and depression anxiety stress scales (DASS)] parameters. Psychological distress (GHQ-12>3) decreased significantly at follow-up, with 11.5% and 53.8% of patients having psychological distress in groups B and C, respectively, versus baseline (p<0.001). mMRC score, SGRQ score, FEV1 and 6-MWD significantly improved in all three groups. Improvement in mMRC and SGRQ was maximal in group B when compared with the other groups. PDT, CSCL, and WHO-QOL-Bref-26 scores improved significantly at follow-up in all three groups, with maximum improvement in group B, followed by group C, and then group A. The DASS score also improved maximally in group B. Patients should be screened for psychological co-morbidities using simple screening tools. PR plays an important role in improving the psychology of COPD patients. However, results are better with directed psycho-educative sessions by non-experts and best with definitive treatment by psychiatrists.