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Yong Chen,1 Yan-Juan Chen,1 Jian-Feng Luo,2 Mang He,1 Si-Jin Zhao,3 Shi-Dan Tian,1 Yong-Qiao Zhang,3 Xiao-Long Chen,3 Chuan-Jie Yang,3 Yu-Zhuo Luo,3 Kutty Selva Nandakumar,4 Mei Tian1 1Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 2Department of Biostatistics, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3The First School of Clinical Medicine, Zunyi Medical University, Zunyi, People’s Republic of China; 4Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, SwedenCorrespondence: Mei Tian, Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi City, Guizhou Province, 563000, People’s Republic of China, Email 348820517@qq.com Kutty Selva Nandakumar, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden, Email ksnandakumar@outlook.comPurpose: The quality of life (QoL) of elderly patients with rheumatoid arthritis (RA) in Zunyi China based on health parameters has not been previously analyzed. This study compares the 36-Item Short Form Health Survey (SF-36) scores and prevailing health complications between < 60y and ≥ 60y patients with RA. Data from 1166 patients with RA who visited the rheumatology department of Zunyi Medical University Hospital were followed up and retrospectively analyzed.Patients and Methods: Data from 1166 patients with RA who visited the rheumatology department of Zunyi Medical University Hospital (2021.1– 2022.8) were followed up and retrospectively analyzed.Results: Twenty cases passed away at 61.55 ± 8.11y, which was 6.75 years less than the local average age of death. Elderly patients with RA reported lower recovery levels, and their levels of inflammatory markers such as Immunoglobulin M-rheumatoid factor (IgM-RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were significantly higher than those of younger patients during their past one-year observation period. The SF-36 results indicated that eight items of QoL in the elderly patients were all significantly inferior to < 60y patients, while the complications of interstitial lung disease (ILD), latent tuberculosis infection (LTBI) and, lung and herpes zoster infections were significantly higher.Conclusion: Elderly patients had a higher disease activity along with poor QoL, more health-related complications, and susceptibility to infections. Our study emphasizes the imperative need for optimization of RA treatment modalities in the elderly to alleviate their sufferings.Keywords: elderly rheumatoid arthritis, SF-36 scores, clinical characteristics, treatment outcomes

Abstract Diabetic Peripheral Neuropathy (DPN) is a nerve damage that is treated with painkillers and steroids which have the drawback of interference with other medications and the dangers of side effects. Novelty of the proposed work is to develop a Near Infrared Region (NIR) based non-invasive therapy device called ‘DPNrelief-1.0V’developed with a 890 nm wavelength diodes. DPNrelief-1.0V delivers a total dosage of 6.174 J/cm2 with heat absorption by tissue of 61.74 Joules at 30 minutes. The device was tested by carrying out a pilot study with 8 patients where 4 were treatment group and control group. The DPNrelief-1.0V is validated by Nerve Conduction Study (NCS) test. The degenerated nerves pre-therapy showed less amplitude, Conduction Velocity (CV) and latency which was improved post-therapy by 100% in amplitude of nerve signal, 100% in CV and a decrease of 36.2% in latency. Independent t-test was conducted to find the difference between control and treatment, wherein a p value

Abstract In Huntington’s Disease (HD) and related disorders, expansion of CAG trinucleotide repeats produces a toxic gain of function in affected neurons. Expanded huntingtin (expHTT) mRNA forms aggregates that sequester essential RNA binding proteins, dysregulating mRNA processing and translation. The physical basis of RNA aggregation has been difficult to disentangle owing to the heterogeneous structure of the CAG repeats. Here, we probe the folding and unfolding pathways of expHTT mRNA using single-molecule force spectroscopy. Whereas normal HTT mRNAs unfold reversibly and cooperatively, expHTT mRNAs with 20 or 40 CAG repeats slip and unravel non-cooperatively at low tension. Slippage of CAG base pairs is punctuated by concerted rearrangement of adjacent CCG trinucleotides, trapping partially folded structures that readily base pair with another RNA strand. We suggest that the conformational entropy of the CAG repeats, combined with stable CCG base pairs, creates a stick-slip behavior that explains the aggregation propensity of expHTT mRNA.

Yong Chen,1 Mang He,1 Si-Jin Zhao,2 Yan-Juan Chen,1 Yong-Qiao Zhang,2 Xiao-Long Chen,2 Chuan-Jie Yang,2 Yu-Zhuo Luo,2 Kutty Selva Nandakumar,3 Zhou-Xiong Xing,4 Mei Tian1 1Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 2Undergraduate Students of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 3Docent, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; 4Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaCorrespondence: Mei Tian; Zhou-Xiong Xing, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi City, Guizhou Province, People’s Republic of China, Email 348820517@qq.com; xingzhouxiong111@126.comPurpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS).Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect.Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL.Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.Keywords: real-world study, rheumatoid arthritis, traditional Chinese medicine, disease activity, hydroxychloroquine

Background: Wound healing is a complex, multifactorial process in which poor healing in chronic wounds has emerged as the most significant complication in recent years. Jojoba oil (JO) has been traditionally used for its medicinal properties, especially for skin disorders. Studies suggested its potential wound-healing activity in-vitro. However, the underlying mechanism by which JO promotes the rejuvenating process is unclear in-vivo. The present study was aimed at evaluating the wound-healing activity of JO in both normal and delayed healing. Methods: Excision wounds were inflicted by surgical method on the anesthetized rats. Animal wounds were explored for their healing activity by photography in-vivo. Expression of ERK, collagen, VEGF and PDGF was investigated using western blot. Results: Topical administration of JO (0.5 ml/wound, twice a day) showed significant wound healing activity. All groups demonstrated a significant increase (p

Background: Obstructive sleep apnea (OSA) and insomnia are both associated with suicidal ideation (SI), but it is not known if co-morbid insomnia and obstructive sleep apnea (COMISA) has a synergistic effect. We aim to study the association of symptoms of insomnia, OSA, and COMISA with self-reported risk of SI and/or self-harm. Methods: Using cross-sectional data from the National Health and Nutrition Examination Survey (2005–2008) (n = 5,834), we examined the odds of self-reported risk of SI and/or self-harm (past 12-months) with insomnia symptoms, high-risk for OSA, and probable COMISA groups. Insomnia symptoms were identified as having trouble attaining sleep, awakening in between sleep, early awakening on more than 15 nights/month, or diagnosed by physician. High-risk for OSA was assessed by commonly used STOP-Bang questionnaire. Probable COMISA was identified if respondents had both insomnia symptoms and high-risk for OSA. Multiple logistic regression analyses examined the associations, both unadjusted and adjusted for demographics, health behaviors, and depressive symptoms. Results: Self-reported risk of SI and/or self-harm was likely to be more common among respondents with probable COMISA (AOR 3.24, 95 % CI 1.78–5.87) relative to respondents with no sleep disorder symptoms. The increase in odds for self-reported risk of SI and/or self-harm with probable COMISA compared to insomnia symptoms or high-risk for OSA alone suggests an underlying synergistic effect (Synergy Factor = 2.38). Conclusion: COMISA is associated with increased risk of SI and/or self-harm. Suicide prevention efforts should focus on multimorbidity (two or more physical/mental medical conditions) to identify high-risk groups.

Background: Sesamol (3,4-methylenedioxyphenol) is one of the plant compounds tested in vivo for diabetic wound healing, normal wound healing, and dexamethasone-induced delayed wound healing. Elucidation of mechanisms underlying the wound healing effect of sesamol through modulation of various molecular and cellular pathways is the crux of this paper. Objectives: The objective of the current work was to uncover the mechanism of sesamol underlying the treatment of diabetic wounds using gene expression analysis. Methods: The cytotoxicity assay was performed using an SRB colorimetric assay, from which two doses were selected for further studies. The expression of various molecular markers was performed using RT-PCR. Results: An SRB assay was carried out to identify the safe concentration of molecules in HDDF cell lines. Two doses that showed more than 80 % viability were selected and used for gene expression analysis. It was observed that sesamol enhanced the expression of VEGF, TGFβ, AKT, JNK, ERK, and TIMP3 significantly (P≤0.001, P≤0.05, P≤0.001, P≤0.0001) when compared to control and significantly (P≤0.0001) downregulated the expression of MMP2, MMP-9 when compared to control, which promote wound healing in diabetes. The migration studies also showed a significant increase when compared to the control. Conclusion: Sesamol (SM) is a promising molecule that can accelerate wound healing in diabetes by modulating different markers involved in the process.

Key Clinical Message This case demonstrated the rare “shark fin” ECG pattern, an ST‐segment elevation typically seen in acute myocardial infarction. We reported a case of takotsubo cardiomyopathy secondary to influenza A infection with multiple organ failure, showing the shark fin sign and resulting in in‐patient mortality and various complication.

Background Task-sharing of spinal anaesthesia care by non-specialist graduate physicians, termed medical officers (MOs), is commonly practised in rural Indian healthcare facilities to mitigate workforce constraints. We sought to assess whether spinal anaesthesia failure rates of MOs were non-inferior to those of consultant anaesthesiologists (CA) following a standardised educational curriculum.Methods We performed a randomised, non-inferiority trial in three rural hospitals in Tamil Nadu and Chhattisgarh, India. Patients aged over 18 years with low perioperative risk (ASA I & II) were randomised to receive MO or CA care. Prior to the trial, MOs underwent task-based anaesthesia training, inclusive of remotely accessed lectures, simulation-based training and directly observed anaesthetic procedures and intraoperative care. The primary outcome measure was spinal anaesthesia failure with a non-inferiority margin of 5%. Secondary outcome measures consisted of incidence of perioperative and postoperative complications.Findings Between 12 July 2019 and 8 June 2020, a total of 422 patients undergoing surgical procedures amenable to spinal anaesthesia care were randomised to receive either MO (231, 54.7%) or CA care (191, 45.2%). Spinal anaesthesia failure rate for MOs (7, 3.0%) was non-inferior to those of CA (5, 2.6%); difference in success rate of 0.4% (95% CI=0.36–0.43%; p=0.80). Additionally, there were no statistically significant differences observed between the two groups for intraoperative or postoperative complications, or patients’ experience of pain during the procedure.Interpretation This study demonstrates that failure rates of spinal anaesthesia care provided by trained MOs are non-inferior to care provided by CAs in low-risk surgical patients. This may support policy measures that use task-sharing as a means of expanding anaesthesia care capacity in rural Indian hospitals.Trial registration number NCT04438811.

The Janus MoSSe and alloy MoSxSe(1-x), belonging to the family of two-dimensional (2D) transition metal dichalcogenides (TMDs), have gained significant attention for their potential applications in nanotechnology. The unique asymmetric structure of Janus MoSSe provides intriguing possibilities for tailored applications. The alloy MoSxSe(1-x) offers a tunable composition, allowing for the fine-tuning of the properties to meet specific requirements. These materials exhibit remarkable mechanical, electrical, and optical properties, including a tunable band gap, high absorption coefficient, and photoconductivity. The vibrational and magnetic properties also make it a promising candidate for nanoscale sensing and magnetic storage applications. Properties of these materials can be precisely controlled through different approaches such as size-dependent properties, phase engineering, doping, alloying, defect and vacancy engineering, intercalation, morphology, and heterojunction or hybridisation. Various synthesis methods for 2D Janus MoSSe and alloy MoSxSe(1-x) are discussed, including hydro/solvothermal, chemical vapour transport, chemical vapour deposition, physical vapour depositio, and other approaches. The review also presents the latest advancements in Janus and alloy MoSSe-based applications, such as chemical and gas sensors, surface-enhanced Raman spectroscopy, field emission, and energy storage. Moreover, the review highlights the challenges and future directions in the research of these materials, including the need for improved synthesis methods, understanding of their stability, and exploration of new applications. Despite the early stages of research, both the MoSSe-based materials have shown significant potential in various fields, and this review provides valuable insights for researchers and engineers interested in exploring its potential.

Abstract Cognitive dysfunction is common in Parkinson’s disease (PD). We developed and evaluated an EEG-based biomarker to index cognitive functions in PD from a few minutes of resting-state EEG. We hypothesized that synchronous changes in EEG across the power spectrum can measure cognition. We optimized a data-driven algorithm to efficiently capture these changes and index cognitive function in 100 PD and 49 control participants. We compared our EEG-based cognitive index with the Montreal cognitive assessment (MoCA) and cognitive tests across different domains from National Institutes of Health (NIH) Toolbox using cross-validations, regression models, and randomization tests. Finally, we externally validated our approach on 32 PD participants. We observed cognition-related changes in EEG over multiple spectral rhythms. Utilizing only 8 best-performing electrodes, our proposed index strongly correlated with cognition (MoCA: rho = 0.68, p value

This article proposes a novel zero-voltage switching (ZVS) and zero-current switching (ZCS)-based hybrid dc circuit breaker for a radar power system. Long-range radars demand huge power, in the order of hundreds of kW. Radar's phased array antenna houses a large number of electronic devices and works primarily on a dc power supply. Typically, military systems are required to have the highest operational reliability, as a result, electrical system protection plays a crucial role. A high power 310 V dc electrical power grid in radar carries hundreds of amperes of current under nominal operating conditions, results in significant fault current due to very low impedance, and demands a very fast fault interruption device. This article proposes and demonstrates the complete operation of a hybrid dc circuit breaker topology for radar applications. The proposed dc circuit breaker employs a mechanical switch that carries the entire current during the nominal operating conditions, and a power electronic module (PEM) connected in parallel helps in diverting the fault current from the main path. Fault current transfers to the PEM branch in a fraction of a second (5 $\mu s$), which ensures faster load-side isolation. During the fault interruption process, mechanical switch contact opening experiences both ZVS and ZCS features, resulting in arcless operation, and also helps in faster contact separation. The ZVS and ZCS features greatly improve the reliability of the mechanical switch. The proposed concept does not involve any capacitors or corresponding precharging circuits for the ZVS/ZCS features. The proposed dc circuit breaker is analyzed theoretically, and also by simulations in LTspice. Additionally, an experimental prototype with a dc system rating of 310 V–10 A is developed to experimentally validate the performance of the proposed breaker topology. The article also presents a detailed design and comparative analysis, along with a discussion on the limitations of the proposed dc circuit breaker, and the scope for improvements.

As a chronic illness, tuberculosis is known to negatively affect patients' day-to-day functioning. Therefore, evaluating all aspects of their health is imperative to improve their quality of life. The current study was conducted to assess the quality of life of patients receiving tuberculosis therapy and to identify the associated risk factors. A prospective, cross-sectional study of six months was planned and conducted in 66 Mycobacterium tuberculosis-infected patients who justified the pre-defined inclusion criteria. All pertinent data about the patients were collected in a precisely created data collection form. Further, the brief version of the World Health Organization Quality of Life Questionnaire was used to evaluate the patients’ quality of life. Of the 66 patients who were enrolled, 42 (63.6%) were male, and 14 (21.2%) belonged to the age group of 61-70 years. The domains of physical, psychological, social relationships, and environment had mean scores of 46.76±20.15 standard deviation (SD), 55.02±16.12 SD, 54.83±13.91 SD, and 64.92±14.59 SD, respectively. All four quality-of-life domains were found to have statistically significant associations with a variety of sociodemographic and treatment-related variables. This study gives healthcare practitioners an insight into the need to evaluate patients' health-related quality of life, particularly for individuals with chronic illnesses.

Abstract Asherman’s Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman’s Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman’s Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.

Abstract Calcineurin inhibitors such as cyclosporine and tacrolimus are immunosuppressant drugs that are known to induce tremors. Non-calcineurin inhibitors such as sirolimus and everolimus have also reportedly been accompanied by tremors, albeit less likely. However, the prevalence rates reported in the literature are notably wide, and the risk profiles for these drug-induced tremors are less understood. We searched PubMed to extract data on the risk of tremors with these drugs when prescribed for various transplant and non-transplant indications. We ascertained whether the risk of drug-induced tremor is influenced by the underlying diagnosis, dosing formulations, drug concentrations, and blood monitoring. We extracted data on treatment strategies and outcomes for tremors. Articles were primarily screened based on English language publications, abstracts, and studies with n ≥ 5, which included case series, retrospective studies, case-controlled studies, and prospective studies. We found 81 eligible studies comprising 33 cyclosporine, 43 tacrolimus, 6 sirolimus, and 1 everolimus that discussed tremor as an adverse event. In the pooled analysis of studies with n > 100, the incidence of tremor was 17% with cyclosporine, 21.5% with tacrolimus, and 7.8% with sirolimus and everolimus together. Regarding the underlying diagnosis, tremor was more frequently reported in kidney transplant (cyclosporine 28%, tacrolimus 30.1%) and bone marrow transplant (cyclosporine 40%, tacrolimus 41.9%) patients compared with liver transplant (cyclosporine 9%, tacrolimus 11.5%) and nontransplant indications (cyclosporine 21.5%, tacrolimus 11.3%). Most studies did not report whether the risk of tremors correlated with drug concentrations in the blood. The prevalence of tremors when using the twice-daily formulation of tacrolimus was nearly the same as the once-daily formulation (17% vs 18%). Data on individual-level risk factors for tremors were lacking. Except for three studies that found some benefit to maintaining magnesium levels, there were minimal data on treatments and outcomes. A large body of data supports a substantive and wide prevalence of tremor resulting from tacrolimus use followed by cyclosporine, especially in patients receiving a kidney transplant. However, there is little reporting on the patient-related risk factors for tremor, risk relationship with drug concentrations, treatment strategies, and outcomes.

Abstract Energy storage and mobility industries use polypropylene (PP) nanocomposites. The energy storage applications of newly made microporous SiO2 filled, porous PP nanocomposites combining PP, natural rubber, and SiO2 nanoparticles then subsequently removing natural rubber from the nanocomposite were explored in this paper. SEM pictures showed how the pore morphology was altered by nanofillers. Mechanical tensile tests reveal that the SiO2 nanofiller enhances the mechanical properties of microporous polypropylene. XRD and DSC experiments have shown that SiO2 nanoparticles works as a nucleating agent but has no impact on the crystallinity of PP. The electrolyte absorption, porosity, ionic conductivity, wettability and charge–discharge performance were investigated for PP/SiO2 nanocomposite separator. SiO2 nanoparticles in the matrix have a significant impact on the wettability of PP membrane, since the presence of SiO2 nanoparticle reduces the contact angle from 24° to 15°. SiO2 filled PP membrane outperformed microporous PP and celgard separator in terms of electrolyte uptake (230%) and porosity (62%). In comparison to microporous PP, the PP/SiO2 membrane demonstrated a better ionic conductivity (5.9 × 10−4 S cm−1). Finally, Li/PP‐SiO2/LiFePO4 coin cells (2320 type) were fabricated and delivered a discharge capacity of 138 mAh g−1.

Abstract Black patients are diagnosed with Parkinson’s disease (PD) at half the rate as White patients. The reasons for this large disparity are unknown. Here, we review evidence that practitioner bias may contribute. A key sign of PD is hypomimia or decreased facial expressivity. However, practitioner bias surrounding facial expressivity in Black people versus White people may lead practitioners to appraise Black patients with hypomimia as having higher levels of facial expressivity. Furthermore, practitioner bias may cause them to characterize reduced facial expressivity as being due to negative personality traits, as opposed to a medical sign, in Black patients with hypomimia. This racial bias in the evaluation of hypomimia in Black versus White patients could profoundly impact subsequent referral decisions and rates of diagnosis of PD. Therefore, exploring these differences is expected to facilitate addressing health care disparities through earlier and more accurate detection of PD in Black patients.

Abstract Background Surgical site infections (SSIs) affect around a third of patients undergoing surgeries worldwide, annually. It is heterogeneously distributed with a higher burden in low and middle-income countries. Although rural and semi-urban hospitals cater to 60–70% of the Indian population, scarce data regarding SSI rates are available from such hospitals. The study aimed to determine the prevalent SSI prevention practices and existing SSI rates in the smaller rural and semi-urban hospitals in India. Methods This is a prospective study performed in two phases involving surgeons and their hospitals from Indian rural and semi-urban regions. In the first phase, a questionnaire was administered to surgeons enquiring into the perioperative SSI prevention practices and five interested hospitals were recruited for phase two which documented the rate of SSIs and factors affecting them. Results There was full compliance towards appropriate perioperative sterilisation practices and postoperative mop count practice at the represented hospitals. But prophylactic antimicrobials were continued in the postoperative period in more than 80% of the hospitals. The second phase of our study documented an overall SSI rate of 7.0%. The SSI rates were influenced by the surgical wound class with dirty wounds recording six times higher rate of infection than clean cases. Conclusions SSI prevention practices and protocols were in place in all the less-resourced hospitals surveyed. The SSI rates are comparable or lower than other LMIC settings. However, this is accompanied by poor implementation of the antimicrobial stewardship guidelines.

ABSTRACT Serum titers of SARS-CoV-2-neutralizing antibodies (nAbs) correlate well with protection from symptomatic COVID-19 but decay rapidly in the months following vaccination or infection. In contrast, measles-protective nAb titers are lifelong after measles vaccination, possibly due to persistence of the live-attenuated virus in lymphoid tissues. We, therefore, sought to generate a live recombinant measles vaccine capable of driving high SARS-CoV-2 nAb responses. Since previous clinical testing of a live measles vaccine encoding a SARS-CoV-2 spike glycoprotein resulted in suboptimal anti-spike antibody titers, our new vectors were designed to encode prefusion-stabilized SARS-CoV-2 spike glycoproteins, trimerized via an inserted peptide domain, and displayed on a dodecahedral miniferritin scaffold. Additionally, to circumvent the blunting of vaccine efficacy by preformed anti-measles antibodies, we extensively modified the measles surface glycoproteins. Comprehensive in vivo mouse testing demonstrated the potent induction of high titer nAbs in measles-immune mice and confirmed the significant contributions to overall potency afforded by prefusion stabilization, trimerization, and miniferritin display of the SARS-CoV-2 spike glycoprotein. In animals primed and boosted with a measles virus (MeV) vaccine encoding the ancestral SARS-CoV-2 spike, high-titer nAb responses against ancestral virus strains were only weakly cross-reactive with the Omicron variant. However, in primed animals that were boosted with a MeV vaccine encoding the Omicron BA.1 spike, antibody titers to both ancestral and Omicron strains were robustly elevated, and the passive transfer of serum from these animals protected K18-ACE2 mice from infection and morbidity after exposure to BA.1 and WA1/2020 strains. Our results demonstrate that by engineering the antigen, we can develop potent measles-based vaccine candidates against SARS-CoV-2.IMPORTANCEAlthough the live-attenuated measles virus (MeV) is one of the safest and most efficacious human vaccines, a measles-vectored COVID-19 vaccine candidate expressing the SARS-CoV-2 spike failed to elicit neutralizing antibody (nAb) responses in a phase-1 clinical trial, especially in measles-immune individuals. Here, we constructed a comprehensive panel of MeV-based COVID-19 vaccine candidates using a MeV with extensive modifications on the envelope glycoproteins (MeV-MR). We show that artificial trimerization of the spike is critical for the induction of nAbs and that their magnitude can be significantly augmented when the spike protein is synchronously fused to a dodecahedral scaffold. Furthermore, preexisting measles immunity did not abolish heterologous immunity elicited by our vector. Our results highlight the importance of antigen optimization in the development of spike-based COVID-19 vaccines and therapies.

Sickness behaviour, a set of behavioural changes associated with neuroinflammation, is expressed as decreased mobility and depressed behaviour. Activation of AMP-activated protein kinase (AMPK) is reported to regulate inflammation in conditions such as Alzheimer and traumatic brain injury. Metformin, an antidiabetic agent acting via AMPK activation, possesses anti-inflammatory properties. Similarly, the reported anti-inflammatory activities of berberine could be partially attributed to its ability to activate AMPK. In this study, we investigated the effects of metformin and berberine against lipopolysaccharide (LPS)-induced sickness-like behaviour, associated with neuroinflammation, impaired cognition, and oxidative stress. Swiss albino mice were divided into four groups, normal control, LPS control, metformin treatment, and berberine treatment. The control groups received saline for 7 days. Groups 3 and 4 received metformin (200 mg/kg) and berberine (100 mg/kg), respectively, orally once daily for 7 days. On day 7, 1 h after the treatments, animals received LPS (1.5 mg/kg i.p.) to induce sickness-like behaviour. Open field test (OFT) and forced swim test (FST), were performed within 2 h of LPS administration. Then, proinflammatory cytokines (IL-1β and TNF-α), acetylcholinesterase activity (AChE), and oxidative stress markers were estimated in the brain homogenate. In the LPS control group, immobility state, proinflammatory cytokines, AChE, and lipid peroxidation were significantly increased, whereas the glutathione levels were decreased. Pretreatment with metformin significantly improved immobility in the FST, with reduced IL-1β, oxidative stress markers, and AChE activity. However, no significant changes were observed in OFT. Berberine pretreatment exhibited only an apparent, statistically insignificant, improvement in sickness-like behaviour assessed using FST and OFT, cytokine levels, oxidative markers, and AChE. Several factors affect treatment efficacy, such as treatment duration and administered dose. Considering these, berberine warrants elaborate preclinical evaluation for neuroinflammation. Nevertheless, based on the effects observed, AMPK activators could regulate neuroinflammation, cognition, and oxidative stress linked with sickness-like behaviour.

Parkinson’s disease (PD) is a neurodegenerative disease with cognitive as well as motor impairments. While much is known about the brain networks leading to motor impairments in PD, less is known about the brain networks contributing to cognitive impairments. Here, we leveraged resting-state functional magnetic resonance imaging (rs-fMRI) data from the Parkinson’s Progression Marker Initiative (PPMI) to examine network dysfunction in PD patients with cognitive impairment. We focus on canonical cortical networks linked to cognition, including the salience network (SAL), frontoparietal network (FPN), and default mode network (DMN), as well as a subcortical basal ganglia network (BGN). We used the Montreal Cognitive Assessment (MoCA) as a continuous index of coarse cognitive function in PD. In 82 PD patients, we found that lower MoCA scores were linked with lower intra-network connectivity of the FPN. We also found that lower MoCA scores were linked with lower inter-network connectivity between the SAL and the BGN, the SAL and the DMN, as well as the FPN and the DMN. These data elucidate the relationship of cortical and subcortical functional connectivity with cognitive impairments in PD.

India is known for its rich cultural heritage with different cultures and customs. Indian historical traditions and cultures were molded in a manner that most older adults were cared for at home by their children. However, India is being urbanized and developing swiftly changing its socio-cultural scenarios. With globalization and the increased popularity of social media, the youth is more ambitious than ever and is ready to migrate and explore. Fueled by the rapid aging of the global population, demand is escalating for robust programs, policies, and activities to improve the lives of older adults. However, most of these schemes have not yet been fully implemented nationwide; several state governments have yet to realize their full potential due to the lack of resources and competing priorities. Aligning with the UN’s healthy aging agenda, several programs and policies in India are contributing toward ensuring quality aged care services. This paper explores the challenges and opportunities for effective ground-level translation from precepts to practice.

OBJECTIVES/GOALS: Inexpensive, accurate home monitoring is the standard-of-care in many diseases like hypertension or diabetes; however, it has yet to be widely used in neurodegenerative diseases. We used wearable activity monitors and computer-vision evaluated assessments to estimate Parkinson’s disease (PD)-related disease burden. METHODS/STUDY POPULATION: We recruited 22 people from the University of Iowa Movement Disorders Clinic. Each person completed a standardized set of 3 fine motor tasks using their hands. We recorded a video of this activity, which was evaluated using MediaPipe - an open-source pose classification program from Alphabet - as well as had an nurse-practitioner evaluate the performance on a validated scale (UPDRS). Participants wore a Fitbit Inspire 3 activity tracker at home for the next two weeks. We quantified disease burden using the Parkinson’s Disease Questionnaire 39 - a validated 39-item survey about the intensity of PD-related impairment. Using data from the videos and activity trackers, we estimated 1) the standardized UPDRS assessment of motor impairment and 2) the total PDQ-39 score. RESULTS/ANTICIPATED RESULTS: We found observationally recorded fastest sustained (at least 5 minutes) walking speed was a strong predictor of PDQ-39, explaining over one third of the variability in the measure. Range of motion in the videos was a significant predictor of UPDRS scores; however, was only weakly related to the overall PDQ-39 score. Further processing of the signals from the video, including wavelets and frequency domain analysis, may provide better predictive capabilities. PDQ-39 subscores (e.g., cognition, social support, mobility) will be the subject of further analysis. DISCUSSION/SIGNIFICANCE: Home monitoring has become the standard in other fields because of the better generalizability of home measurements. Improving the detection and evaluation of PD using home monitoring will lead to more timely and accurately changes in medication and less need for clinic visits - especially off levodopa.

Rinse-off cosmetics containing plastic microbeads are banned worldwide owing to its toxic effects on the water bodies. Therefore, novel seaweed polysaccharide-based microbeads are fabricated as an alternative to the plastic microbead, to be used in exfoliating biocosmetic products. A unique combination of sodium alginate from brown algae, ulvan from green algae in a 1:1 ratio exhibited excellent spherical morphology among the biopolymers screened (sodium alginate, carrageenan, and ulvan) and curcumin was loaded to this best combination. The resulting formulation exhibited 99.2% encapsulation efficiency, significant curcumin release (∼50% in 30 min), stability and biodegradation with appropriate swelling index. Spectral and thermal analysis showed the interaction of curcumin and polysaccharides. Microbeads showed good radical scavenging and antimicrobial activity. Cell viability study revealed that 1.2 mg/ml of microbeads was safe dose to be used in skin care products. The microbeads and bio polysaccharides hold an added value by improving the solubility of curcumin. Hence the novel microbeads would be a potential substitute for hazardous plastic microbeads used in exfoliating skincare products, with antioxidant and anti-microbial activity, revitalizing the traditional use of curcumin.

Introduction It is controversial when to pursue carotid artery stenting (CAS) after acute tandem occlusion (TO) strokes treated with endovascular thrombectomy (EVT). We conducted a retrospective observational study to evaluate the clinical and safety outcomes of emergent versus delayed CAS in the first week of EVT. Methods In this retrospective cohort study, using 2016‐19 Nationwide Readmissions Database, we identified patients with acute ischemic stroke who had EVT for anterior circulation large vessel occlusions (LVOs) and CAS up to 7 days of EVT. CAS performed on day ‐1, 0 or 1 day after admission was considered as emergent CAS. CAS performed 2‐7 days after EVT was defined as delayed CAS. The primary clinical outcomes were all‐cause mortality during same admission. Secondary safety outcomes included intracranial hemorrhage (ICH), seizures, gastric tube (G‐tube) insertion, > 24‐hours mechanical ventilation, tracheostomy, length of stay (LOS), and discharge location (home vs. others). Multivariate logistic regression analysis was used to compare outcomes in emergent CAS group in comparison to delayed CAS group. Age, sex, hypertension, diabetes mellitus, hyperlipidemia, and use of thromobolytics were considered as covariates. Results We identified total of 1990 hospitalizations meeting the study inclusion criteria (mean age: 67 years ± standard deviation:12 years, female 612 (31%). Of these, 1745 (87%) had undergone emergent CAS with EVT and 245 (13%) had delayed CAS (2‐7 days) pos‐EVT. Baseline characteristics were similar between the two cohorts. Delayed CAS cohort had significantly less mortality rates [6 vs 13%; OR 0.43, 95% CI 0.24‐0.78], less ICH [20 vs 30%; OR 0.6, 95% CI 0.43‐0.82¬¬], less cerebral edema [16 vs 23%; OR 0.65, 95% CI 0.44‐0.96], and less mechanical ventilation for >24‐hours [11 vs 18%; OR 0.54, 95% CI 0.34‐0.85]. There was no significant difference between the two treatment groups for tracheostomy, G‐tube placements, new‐onset seizure, and mean LOS. Conclusion Delaying CAS for 2‐7 days after EVT might be a safer approach for endovascular revascularization in anterior circulation LVO strokes secondary to tandem lesions.

Introduction Acute large vessel occlusions (LVOs) represent one‐third of acute ischemic strokes (AIS). LVOs are associated with high mortality and severe functional deficits. Several factors have been reported to play a role in improving outcomes after Endovascular Thrombectomy (EVT). Previous animal studies indicated that statins may have a protective effect on vessel wall injury caused by mechanical thrombectomy. We conducted a retrospective study to analyze whether pretreatment with statins influence the clinical and safety outcomes of EVT in AIS. Methods We conducted a retrospective observational study using the TriNetX database, a global health research network that provides access to electronic medical records retrieved from multiple international healthcare organizations but predominantly from the United States. We collected data about patients' diagnoses (using ICD‐10‐CM codes), medical procedures, medications, and demographics. Investigators were blinded to patients’ personal information or identification of participating healthcare organizations. Our study included adult patients with AIS who received EVT treatment (either extirpation or dilation procedure) between January 4, 2018, and December 31, 2022. The study patients were categorized into two groups based on whether or not they were on statins (Rosuvastatin, Simvastatin, Pravastatin, Atorvastatin, Lovastatin or Pitavastatin) during 3 months prior to hospitalization for AIS. Thirty‐day timepoint assessment was chosen to analyze the primary outcome (all‐cause mortality) and secondary outcomes [intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), decompressive hemicraniectomy procedure (DHC), and aspiration pneumonia]. The chi‐square χ2 test was used to analyze baseline characteristics for categorical variables and the independent‐sample t‐test was used for continuous variables. Matching propensity scores (with a tolerance level of 0.01 and the difference between propensity scores ≤ 0.1) were used to control differences in the comparison cohorts. Results We identified 11,972 patients who received EVT for LVO ischemic stroke. A total of 5,839 patients were on statins during 3 months prior to EVT and 6,133 were not on statins. After 1:1 propensity matching, 1,602 patients were included in each group. Kaplan‐Meier survival analysis showed the 30‐day mortality rates were significantly less for patients who were on statins compared to those who were not and with higher survival probability [87.2% vs. 77.5%, hazard ratio 0.54; confidence interval (CI): 0.45,0.64]. In comparison to EVT patients who were not on statins, those who were on statins had significantly lower rates of ICH [9.9 vs 14.1%; odds ratio (OR) 0.67; 95% CI (0.53,0.84)], lower rates of SAH [4.1 vs. 6.3%; OR 0.64; 95% CI (0.46,0.89)] and lower rates of aspiration pneumonia [5.6 vs 8.3%; OR 0.66; 95% CI (0.50,0.88)]. There was no significant difference in rates of DHC in the statins group in comparison to patients who were not on statins [1.8 vs 2.4%; OR 0.74; 95% CI (0.45,1.22)]. Conclusion Pretreatment with statins was associated with significantly better survival, less bleeding risks, and lower complication rates in LVO ischemic strokes post‐EVT. Future studies may help examine the differential effects of statin type and dose intensity on LVO strokes treated with EVT.

IntroductionMetastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint inhibitors (ICIs). Oncolytic viruses (OV) represent a novel approach to immunotherapy for patients with MUM.MethodsWe developed an OV with a Vesicular Stomatitis Virus (VSV) vector modified to express interferon-beta (IFN-β) and Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNβ-TYRP1), and conducted a Phase 1 clinical trial with a 3 + 3 design in patients with MUM. VSV-IFNβ-TYRP1 was injected into a liver metastasis, then administered on the same day as a single intravenous (IV) infusion. The primary objective was safety. Efficacy was a secondary objective.Results12 patients with previously treated MUM were enrolled. Median follow up was 19.1 months. 4 dose levels (DLs) were evaluated. One patient at DL4 experienced dose limiting toxicities (DLTs), including decreased platelet count (grade 3), increased aspartate aminotransferase (AST), and cytokine release syndrome (CRS). 4 patients had stable disease (SD) and 8 patients had progressive disease (PD). Interferon gamma (IFNγ) ELIspot data showed that more patients developed a T cell response to virus encoded TYRP1 at higher DLs, and a subset of patients also had a response to other melanoma antigens, including gp100, suggesting epitope spreading. 3 of the patients who responded to additional melanoma antigens were next treated with ICIs, and 2 of these patients experienced durable responses.DiscussionOur study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM. Although there were no clear objective radiographic responses to VSV-IFNβ-TYRP1, dose-dependent immunogenicity to TYRP1 and other melanoma antigens was seen.

Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated Helicobacter pylori (H. pylori) infection is one of the major reasons for chronic PUD which, if left untreated, may also result in gastric cancer. Treatment of H. pylori is always a challenge to the treating doctor because of the poor bioavailability of the drug at the inner layers of gastric mucosa where the bacteria resides. This results in ineffective therapy and antibiotic resistance. Current treatment regimens available for gastric ulcer and H. pylori infection uses a combination of multiple antimicrobial agents, proton pump inhibitors (PPIs), H2-receptor antagonists, dual therapy, triple therapy, quadruple therapy and sequential therapy. This polypharmacy approach leads to patient noncompliance during long term therapy. Management of H. pylori induced gastric ulcer is a burning issue that necessitates alternative treatment options. Novel formulation strategies such as extended-release gastro retentive drug delivery systems (GRDDS) and nanoformulations have the potential to overcome the current bioavailability challenges. This review discusses the current status of H. pylori treatment, their limitations and the formulation strategies to overcome these shortcomings. Authors propose here an innovative strategy to improve the H. pylori eradication efficiency.

Aims: The present study was conducted to assess the level of medication adherence and factors affecting adherence among Type-2 Diabetes Mellitus (T2DM) patients. Methods: A prospective cross-sectional study was carried out among T2DM patients who were presented to the outpatient department of general medicine. A well-designed data collection form was used to gather information pertaining to various socio-demographic and medical variables. A previously validated and translated 8-item self-reported questionnaire was used to assess the level of medication adherence. Data was analysed using SPSS Version 29.0. Results: Among the total 369 subjects enrolled, a majority were found to be males, and the mean age of the population was observed as 56.84 ± 11.32. A total of 125 (33.8%) subjects were found to be within the category of high adherence, 161 (43.6%) subjects were found to have moderate level of adherence and 83 (22.4%) had low level of adherence. On analysis, various medical variables were found to have a statistically significant association with medication adherence. Conclusion: The findings of the present study would form the basis for all the future implications including education intervention programmes to improve the level of adherence towards anti-diabetic medications, which ultimately results in better health outcomes.

Introduction: The oldest and most popular teaching style in medicine and related fields is the lecture. They are affordable and at least as good at transferring knowledge as other instructional techniques. The present study aimed to assess the effect of lecture-based education, role-playing and learning through peers on learning and satisfaction among MBBS students. Methods: This descriptive study was conducted among the MBBS student studying at MNR Medical College & Hospital. Total of 446 students were approached to fill the predesigned questionnaire for the response. The questionnaire in Google form was shared to students via email, WhatsApp and Telegram (Google form link: https://forms.gle/YfkNojfV5az5Q6AW8). The questionnaire contained two sections, demographic information included age, gender, and year of course and second part included the 10 questions. Students expressed their views on the questionnaire expression based on a five point Likert scale. Results: Total of 340 students with mean age of 19.65±1.22 yrs responded to the questionnaire shared. Among them 61.8% were female students and 38.2% were male students. Most students responded with strongly agree for the role play mode of learning compared to the traditional lecture based learning and also peer learning (p

Abstract Terazosin is an α1-adrenergic receptor antagonist that enhances glycolysis and increases cellular ATP by binding to the enzyme phosphoglycerate kinase 1 (PGK1). Recent work has shown that terazosin is protective against motor dysfunction in rodent models of Parkinson’s disease (PD) and is associated with slowed motor symptom progression in PD patients. However, PD is also characterized by profound cognitive symptoms. We tested the hypothesis that terazosin protects against cognitive symptoms associated with PD. We report two main results. First, in rodents with ventral tegmental area (VTA) dopamine depletion modeling aspects of PD-related cognitive dysfunction, we found that terazosin preserved cognitive function. Second, we found that after matching for demographics, comorbidities, and disease duration, PD patients newly started on terazosin, alfuzosin, or doxazosin had a lower hazard of being diagnosed with dementia compared to tamsulosin, an α1-adrenergic receptor antagonist that does not enhance glycolysis. Together, these findings suggest that in addition to slowing motor symptom progression, glycolysis-enhancing drugs protect against cognitive symptoms of PD.

Abstract Brain rhythms are strongly linked with behavior, and abnormal rhythms can signify pathophysiology. For instance, the basal ganglia exhibit a wide range of low-frequency oscillations during movement, but pathological “beta” rhythms at ~ 20 Hz have been observed in Parkinson’s disease (PD) and in PD animal models. All brain rhythms have a frequency, which describes how often they oscillate, and a phase, which describes the precise time that peaks and troughs of brain rhythms occur. Although frequency has been extensively studied, the relevance of phase is unknown, in part because it is difficult to causally manipulate the instantaneous phase of ongoing brain rhythms. Here, we developed a phase-adaptive, real-time, closed-loop algorithm to deliver optogenetic stimulation at a specific phase with millisecond latency. We combined this Phase-Adaptive Brain STimulation (PABST) approach with cell-type-specific optogenetic methods to stimulate basal ganglia networks in dopamine-depleted mice that model motor aspects of human PD. We focused on striatal medium spiny neurons expressing D1-type dopamine receptors because these neurons can facilitate movement. We report three main results. First, we found that our approach delivered PABST within system latencies of 13 ms. Second, we report that closed-loop stimulation powerfully influenced the spike-field coherence of local brain rhythms within the dorsal striatum. Finally, we found that both 4 Hz PABST and 20 Hz PABST improved movement speed, but we found differences between phase only with 4 Hz PABST. These data provide causal evidence that phase is relevant for brain stimulation, which will allow for more precise, targeted, and individualized brain stimulation. Our findings are applicable to a broad range of preclinical brain stimulation approaches and could also inform circuit-specific neuromodulation treatments for human brain disease.

Industry 4.0 revolutionizes the concept of automation and digitization within the organization leading to immense interest in academia and industry. The digitization of an organization in terms of horizontal, vertical, and end-to-end integration would change the roles an employee discharges in an organization. The main purpose of the paper is to successfully develop an employee adaptability road map for the successful implementation of Industry 4.0. This paper critically analyses the previous studies to develop a roadmap of employee adaptability skills for the successful implementation of Industry 4.0. This study uses deductive methodology using a systematic literature review to group and thematically analyse 52 articles to develop the conceptual model. Besides, this study also ranks these dimensions using an empirical study and finds the most critical employee adaptability dimensions. This is the first systematic literature review and empirical study carried out on employee adaptability skills in Industry 4.0.

The proliferation of electromagnetic (EM) pollution is more rapid now and can be more outrageous in near future due to the exponential growth of the electronics industry. Strategy of using natural fibers for fabricating efficient EMI shielding materials is an environmentally benign solution for this serious peril. With this motivation, we are introducing novel e-textile derived from sustainable jute fabrics that are capable of suppressing and absorbing EM radiations in the frequency range 8.2–12.4 GHz (X-band). In the present work, jute fabrics were in-situ polymerized with pyrrole monomer. These conductive fabrics were then characterized and correlated for their structure, morphology, thermal stability, electrical conductivity, and EMI shielding capabilities. Moreover, this e-textile showcased excellent electrical conductivity of 1.160 S/cm and exhibited a maximum EMI shielding effectiveness value of −30.2 dB (>99.9% blockage) at 1 mm fabric thickness by a predominant absorption behavior with menial reflection or secondary pollution, which is highly beneficial for commercial applications. This is so far the first report of jute fabrics as e-textile with the highest shielding efficacy value reported, which makes them an ideal candidate for next generation of smart and wearable electronic textiles for futuristic applications such as robotics and artificial intelligence (AI).

This paper presents a comprehensive analysis of the consumer-centric business model for rooftop solar PV installations in India. We explore areas where potential policy interventions may be introduced to improve collective stakeholder benefits and incentivize more domestic consumers to adopt rooftop solar power generation in their premises. The proposed policy framework optimizes Feed-in Tariff (FiT) rates, PV capacities and Average Billing Rates (ABRs) towards maximizing stakeholder benefits. The stakeholders considered are the consumers/prosumers and the utility. Case studies with three residential prosumers of different demand and generation profiles are presented. The models for utility profit and prosumer savings are developed, and a multi-objective problem is formulated with FiT, generation capacity (as a function of demand) and ABR as decision variables. The pareto-optimal front is identified for prosumer and utility benefits and suitable points with reasonable tradeoffs are selected based on sensitivity analysis of the impact on collective welfare. The suitability of prevailing tariff and FiT rates of two Indian utilities namely, MSEDCL and TATA POWER, Delhi are studied, and their impact on prosumer savings and utility profits is brought out. The workflow to fix tariff, FiT and local PV capacities in active residential distribution systems is devised, providing the policymakers an effective decision-making tool.

Background: Adequate knowledge, attitude and practices about the use of antibiotics are essential for effective treatment and the cure of diseases. Objective: To assess the knowledge, attitude and practice towards the use of antibiotics among the outpatients of the general medicine department and to find the factors that are significantly associated with it. Materials and methods: A prospective cross-sectional study of eight months duration was carried out among 263 outpatients, in the department of general medicine. The socio-demographic details pertaining to the patients were collected in a well-designed data collection form. The knowledge, attitude and practice of the subjects were assessed by using previously validated KAP questionnaire. Results: The highest number of subjects were found to be females, 135 (51.3%), and most of the subjects belonged to the age category of 18–34 years, 107 (40.7%). The mean score of knowledge, attitude and practice were found to be 62.74 ± 23.28, 76.96 ± 17.73, and 52.55 ± 14.06 respectively. Age, domiciliary status, educational qualification, occupation, and socio-economic class were found to be the factors significantly associated with knowledge. Factors significantly associated with attitude were found to be age, educational qualification and socio-economic class whereas only educational qualification and occupation were found associated with practice. Conclusion: The results of the current study will serve as the foundation for future implications to enhance public knowledge and perceptions regarding antibiotic usage.

We report the effects of magnetic ordering on the temperature evolution of the Raman modes in nanocrystalline Dy3Fe5O12. The Dy3Fe5O12 was synthesized by an aqueous sol–gel method. X-ray diffraction, Raman spectroscopy and transmission electron microscopy studies revealed the phase purity and nanocrystalline nature. We particularly focused on the spin-phonon coupling mechanism in Dy3Fe5O12, as this interaction can greatly affect the magnetoelectric and multiferroic properties of Dy3Fe5O12. Below TC, four phonon modes from the middle- and high-frequency regions displayed anomalous behavior, which was ascribed to the spin-phonon interaction. The application of the mean-field approach enabled us to quantify the spin-phonon coupling strength for each of these phonon modes. Our study has shown that different phonon modes are coupled to ferromagnetic or antiferromagnetic ordering depending on the type of vibrational motion characteristic for a specific mode. These results significantly enhance the understanding of the complex spin-phonon coupling mechanism and its implications on the multifaceted properties of nanocrystalline Dy3Fe5O12, such as multiferroic, magnetoelectric, and magnetocaloric properties. Moreover, these findings have the potential to drive advancements in the optimization and development of spintronic devices.

Background: Globally, alternative medicine is used widely by most patients for several health challenges. To evaluate the effectiveness and safety of PeaNoc XL Tablet in managing pain and inflammation, a randomized clinical trial and systematic study was designed. PeaNoc XL Tablet has been widely utilized for pain and inflammation management, but no previous studies have examined its efficacy and safety. The aim of this study was to determine the clinical effectiveness and safety profile of PeaNoc XL in patients with arthritis experiencing joint pain and inflammation. Methods: A randomized, controlled, and an open-label trial was conducted. A total of 155 patients (18 to 60 years) with arthritis were enrolled for participation. Using computer-generated random sequences, the study population was divided into two groups in a randomized manner. Group A received Standard therapy and Group B received Standard therapy with PeaNoc XL Tablet 400mg (two tablets OD after food). Results: Out of 155 patients, a total of 83 individuals were excluded from the study, leaving 72 patients who were randomly assigned to either Group A (n=36) or Group B (n=36). The administration of PeaNoc XL as an adjunct to standard therapy resulted in a significant reduction in levels of TNF-α (P

Leucine-rich repeat kinase 2 (LRRK2) is a serine–threonine protein kinase belonging to the ROCO protein family. Within the kinase domain of LRRK2, a point mutation known as LRRK2 G2019S has emerged as the most prevalent variant associated with Parkinson’s disease. Recent clinical studies have indicated that G2019S carriers have an elevated risk of cancers, including colon cancer. Despite this observation, the underlying mechanisms linking LRRK2 G2019S to colon cancer remain elusive. In this study, employing a colitis-associated cancer (CAC) model and LRRK2 G2019S knock-in (KI) mouse model, we demonstrate that LRRK2 G2019S promotes the pathogenesis of colon cancer, characterized by increased tumor number and size in KI mice. Furthermore, LRRK2 G2019S enhances intestinal epithelial cell proliferation and inflammation within the tumor microenvironment. Mechanistically, KI mice exhibit heightened susceptibility to DSS-induced colitis, with inhibition of LRRK2 kinase activity ameliorating colitis severity and CAC progression. Our investigation also reveals that LRRK2 G2019S promotes inflammasome activation and exacerbates gut epithelium necrosis in the colitis model. Notably, GSDMD inhibitors attenuate colitis in LRRK2 G2019S KI mice. Taken together, our findings offer experimental evidence indicating that the gain-of-kinase activity in LRRK2 promotes colorectal tumorigenesis, suggesting LRRK2 as a potential therapeutic target in colon cancer patients exhibiting hyper LRRK2 kinase activity.

The announcement of India’s 2070 net-zero target has demonstrated the power of a credible policy signal and changed the course of India’s climate debate. While the Government of India (GoI) has not specified whether this target refers to carbon-dioxide or all greenhouse gases, the announcement has been a watershed moment in India’s climate policy. From questions related to whether and at what pace should India decarbonize its economy, various actors in India are now aligned towards this target. An important contribution to inform India’s net-zero journey has come through various modelling assessments undertaken by India’s institutions and researchers. While a few economy-wide net-zero modelling assessments are available, a comprehensive and integrated picture woven collaboratively by India’s climate experts is conspicuously missing. It is critical to complement quantitative modelling-based assessments with insightful perspectives of experts on India’s climate policy. Together, modelling based quantitative assessments and insightful qualitative perspectives of climate experts would be an instrumental force that will ensure that the country achieves its net-zero target by understanding synergies and trade-offs, harnessing opportunities, and avoiding risks along the way. This collaborative article discusses various aspects of pathways towards India’s net-zero goal to address the gap in literature by looking at broad and inter-related dimensions of ‘national and sub-national perspectives’, ‘sectoral and technological transitions’ , and ‘enablers’ needed for India’s transition. While the larger net-zero debate relates to all greenhouse gases, we focus on carbon dioxide in our current effort. The assessment aims to inform not just India’s policy makers and stakeholders, but various researchers, practitioners and governments around the world for them to be better aware of the various aspects of India’s net-zero debate. It weaves the perspectives of experts from 24 institutions across the three broad dimensions to give a comprehensive view of a roadmap towards India’s net-zero future.

The transition of the Worldwide Large Hadron Collider Computing Grid (WLCG) storage services to dual-stack IPv6/IPv4 is almost complete; all Tier-1 and 94% of Tier-2 storage are IPv6 enabled. While most data transfers now use IPv6, a significant number of IPv4 transfers still occur even when both endpoints support IPv6. This paper presents the ongoing efforts of the HEPiX IPv6 working group to steer WLCG toward IPv6-only services by investigating and fixing the obstacles to the use of IPv6 and identifying cases where IPv4 is used when IPv6 is available. Removing IPv4 use is essential for the long-term agreed goal of IPv6-only access to resources within WLCG, thus eliminating the complexity and security concerns associated with dual-stack services. We present our achievements and ongoing challenges as we navigate the final stages of the transition from IPv4 to IPv6 within WLCG.

Osteogenic sarcoma is a high-grade tumor with greater preponderance for hematogenous metastasis. The most common sites for metastases are the lungs, bones, and lymph nodes. We present in this case report a 24-year-old man with recurrent high-grade osteogenic sarcoma of the right lower limb with serosal small bowel metastases and necrotizing enterocolitis. Sarcomas are high-grade tumors with an increased incidence of hematogenous metastases. Radiologists in oncological referral centers should be aware of the common as well as the uncommon presentation of all common tumors.

Hyperammonemia is a rare cause of adult episodic encephalopathy. Citrin deficiency resulting in citrullinemia type 2 (CTLN2) can lead to recurrent delirium in adults. Here we report a case of adult onset episodic encephalopathy due to citrin deficiency. A 40 years old male presented with one-year history of episodic encephalopathy triggered by high protein and fat diet. He also had chronic pancreatitis and subacute intestinal obstruction which is a novel manifestation of CTLN2. Evaluation showed elevated blood liver enzymes, ammonia, and citrulline. MRI brain showed frontal hyperintensities and bulky basal ganglia which have not been reported. Diagnosis was confirmed by next-generation sequencing which showed a novel variant c. 1591G > A in exon15 of SLC25A13. Hyperammonemic syndromes should be considered in differential diagnosis of episodic encephalopathy in adults. This report shows novel features of subacute intestinal obstruction and MRI findings in CTLN2 expanding spectrum of manifestation.

IntroductionConventional magnetic resonance imaging (MRI) has limitations in differentiating tumor recurrence (TR) from radionecrosis (RN) in high-grade gliomas (HGG), which can present with morphologically similar appearances. Multiparametric advanced MR sequences and Positron Emission Tomography (PET) with amino acid tracers can aid in diagnosing tumor metabolism. The role of both modalities on an individual basis and combined performances were investigated in the current study.Materials and MethodsPatients with HGG with MRI and PET within three weeks were included in the retrospective analysis. The multiparametric MRI included T1-contrast, T2-weighted sequences, perfusion, diffusion, and spectroscopy. MRI was interpreted by a neuroradiologist without using information from PET imaging. 18F-Fluoroethyl-Tyrosine (FET) uptake was calculated from the areas of maximum enhancement/suspicion, which was assessed by a nuclear medicine physician (having access to MRI to determine tumor-to-white matter ratio over a specific region). A definitive diagnosis of TR or RN was made based on the combination of multidisciplinary joint clinic decisions, histopathological examination, and clinic-radiological follow-up as applicable.Results62 patients were included in the study between July 2018 and August 2021. The histology during initial diagnosis was glioblastoma, oligodendroglioma, and astrocytoma in 43, 7, and 6 patients, respectively, while in 6, no definitive histological characterization was available. The median time from radiation (RT) was 23 months. 46 and 16 patients had TR and RN recurrence, respectively. Sensitivity, specificity, and accuracy using MRI were 98, 77, and 94%, respectively. Using PET imaging with T/W cut-off of 2.65, sensitivity, specificity, and accuracy were 79, 84, and 80%, respectively. The best results were obtained using both imaging combined with sensitivity, specificity, and accuracy of 98, 100, and 98%, respectively.ConclusionCombined imaging with MRI and FET-PET offers multiparametric assessment of glioma recurrence that is correlative and complimentary, with higher accuracy and clinical value.

In orthodontics, patients with hyperdivergent facial types or problems in the vertical dimension are often challenging to treat with predictable treatment results. Conventionally along with fixed appliances, a headgear, posterior bite block, extraction, temporary anchorage devices, or orthognathic surgery are preferable approaches to treat such patients. This case report illustrates a non-extraction, non-surgical orthodontic treatment of 5 mm anterior open bite in a non-growing adult patient, utilizing clear aligner therapy.

Abstract Background Maintaining hemodynamic stability requires constant complex interaction between multiple vascular and extravascular factors. There are varieties of parameters that determine the same and few of them are used to predict the hemodynamic instability at earliest. Shock Index (SI), Modified Shock Index (MSI) and Shock Index-Pediatric age-Adjusted (SIPA) have been studied constantly in different clinical settings. They are best non-invasive measures for early prediction in resource poor setting or at community referral centers. We would like to compare the predictive value of each parameter in our tertiary care center. Methods It was a retrospective study carried out in PICU of a tertiary care centre and includes data collected from 15 August 2019 to 14 August 2021 over a period of 2 years. We recorded demographic data, age, gender, final diagnosis, outcome, and length of stay in PICU. We compared Outcome (Survived/Expired) and length of stay with SI ≥ 0.7 or < 0.7, MSI ≥ 1.3 or < 1.3 and SIPA > 1.22 or < 1.22 (age 4–6 years) > 1 or < 1 (7–12 years) and > 0.9 or < 0.9 (13–16 years). Results This study includes 235 children who were admitted to PICU during study period. The median age was 8 years the median length of stay was 5 days and mortality rate being 11.48% (27). Median SI, MSI were 0.78, 1.6 respectively. 61.70% (145) of patients had SI > 0.7. Median value of SI for septic shock patients was 0.92 on admission. The mortality of the patients with SI > 0.7 was 13.10% (19) and those with MSI > 1.3 was 14.89% (21). Mortality in accordance with SIPA for ages 4–6 years, 7–12 years, and 13–16 years were 15.25% (9), 23% (9) and 19.23% (5) respectively. Basically, SIPA was designed to monitor post trauma cases but in our study we got significant correlation with outcome and length of stay in conditions other than trauma. Conclusions The SI, MSI, and SIPA are simple bedside parameters may be used for prioritizing the patients who require strict monitoring on admission to PICU and intervention whenever required. These parameters were best in predicting the severity of sepsis and septic shock in comparison to other diagnosis. SIPA can be generalised for monitoring any high-risk case.

Introduction Coronavirus disease 2019 (COVID‐19) vaccines have demonstrated efficacy in protecting against severe respiratory distress, averting hospitalization and long‐term sequelae of COVID‐19 infection. The study aimed to determine the effect of COVID‐19 vaccination on mortality and complications due to COVID‐19 associated acute ischemic stroke (AIS). Methods Using TriNetX COVID‐19 research database, patients who had received full vaccination from December 1, 2020, to April 30, 2021, and later had AIS within 30 days of COVID‐19 infection during the period from June 1, 2021, to November 30, 2021, were identified. A control group with unvaccinated COVID‐19 patients with AIS was identified in the same study period. The two groups were matched for demographics and comorbidities with 1:1 propensity score matching. All‐cause mortality was the primary outcome while intracranial hemorrhage (ICH) and venous thromboembolism (VTE) were secondary outcomes at 30 days. Results During the study period, 21814 patients were admitted with AIS within 30 days of COVID‐19 diagnosis: 21233 patients were unvaccinated while 581 patients were vaccinated before their AIS. After propensity score matching, 581 patients in both groups were balanced for relevant characteristics. Patients fully vaccinated prior to acquiring COVID‐19‐associated AIS had lower rates of all‐cause mortality [6.9% (40/581) vs 10.7% (62/581), P = 0.02, hazard ratio = 0.62; 95% confidence interval = 0.41, 0.92)], ICH (3.1% vs 6.9%; OR 0.44, p = 0.005) and VTE (2.9% vs 7.9%; p = 0.0007) when compared with unvaccinated patients. Conclusions Within the limitations of retrospective observational study, prior vaccination for COVID‐19 is associated with improved one‐month survival and reduced complications after COVID‐19 associated AIS.