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Background: Renal involvement, known as lupus nephritis (LN), is a common and serious complication of systemic lupus erythematosus (SLE), linked to significant morbidity and mortality. Histomorphological indices, such as the activity index (AI) and chronicity index (CI), are critical in predicting treatment responses and outcomes. This study aims to compare these histomorphological indices between adult and pediatric patients with LN and evaluate their impact on post-induction therapy outcomes., Methods: A cross-sectional analysis was conducted at a single nephrology department from 2005 to 2019, including patients with biopsy-confirmed LN. Data on demographic characteristics, histomorphological indices, and clinical outcomes post-induction therapy were collected. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States) to identify significant correlations and differences., Results: Pediatric patients exhibited significantly lower AI (p=0.042) and CI scores compared to adults. Lower frequencies of hyaline thrombi (p=0.005) and tubular atrophy (p=0.028) were observed in the pediatric group. Key predictors of a complete response to induction therapy included interstitial inflammation <0.65 and tubular atrophy <0.63. Significant correlations were found between post-induction renal function tests (RFT) and indices such as AI (p=0.035), CI (p<0.001), cellular and fibrocellular crescents (p<0.001), and tubular atrophy (p<0.001). Proteinuria outcomes were significantly associated with CI (p=0.040), interstitial inflammation (p=0.006), and tubular atrophy (p=0.026)., Conclusion: The conclusion aligns with the established understanding that pediatric patients with LN often have a different disease trajectory compared to adults. Pediatric patients generally presented with less severe histomorphological damage, contributing to better responses to induction therapy. Detailed histopathological assessments are essential for guiding treatment strategies and improving patient prognosis in both adult and pediatric LN populations., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Research Committee of Amrita Institute of Medical Sciences issued approval IRB-AIMS-2020-206. 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, Murugesan et al.)

The synaptic tagging and capture (STC) hypothesis lays the framework on the synapse-specific mechanism of protein synthesis-dependent long-term plasticity upon synaptic induction. Activated synapses will display a transient tag that will capture plasticity-related products (PRPs). These two events, tag setting and PRP synthesis, can be teased apart and have been studied extensively-from their electrophysiological and pharmacological properties to the molecular events involved. Consequently, the hypothesis also permits interactions of synaptic populations that encode different memories within the same neuronal population-hence, it gives rise to the associativity of plasticity. In this review, the recent advances and progress since the experimental debut of the STC hypothesis will be shared. This includes the role of neuromodulation in PRP synthesis and tag integrity, behavioural correlates of the hypothesis and modelling in silico . STC, as a more sensitive assay for synaptic health, can also assess neuronal aberrations. We will also expound how synaptic plasticity and associativity are altered in ageing-related decline and pathological conditions such as juvenile stress, cancer, sleep deprivation and Alzheimer's disease. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Introduction: Overactive bladder (OAB) syndrome is a chronic disease characterized by urinary urgency with or without urge incontinence, frequency, and nocturia and antimuscarinic drugs such as solifenacin have been the mainstay of treatment. Mirabegron a beta 3 adrenoreceptor agonist has recently gained importance in the management of OAB. The rationale of the study is that mirabegron improves the storage function without affecting voiding which increases the therapeutic effectiveness. The objective was to determine the therapeutic effectiveness of mirabegron versus solifenacin., Methods: A prospective observational study was conducted on 298 patients with OAB syndrome attending the urology outpatient department of government medical college after obtaining institutional review board clearance. Patients of both genders, belonging to the 18-65 years of age group, attending the urology outpatient department were selected for the study. Patients were evaluated using the OAB-validated 8-question awareness tool (OAB-V8 score) before and after receiving drugs by direct questionnaire method after receiving informed consent. Patients were prescribed either solifenacin 5 mg or mirabegron 25 mg once daily by the urologist. Follow-up was done after 4 and 12 weeks. Adverse drug reactions of the drugs were assessed using the Central Drug Standard Control Organization suspected adverse reaction (ADR) form, and ADRs were notified to the nearest ADR monitoring center., Results: The mirabegron group showed maximum improvement in the mean OAB-V8 score values from baseline at 4 weeks (12.82 ± 5.86, P < 0.001) and 12 weeks (5.74 ± 3.31, P < 0.001) when compared to solifenacin. OAB-V8 scores of the solifenacin group also showed significant improvement from the baseline at 4 weeks (15.30 ± 5.54, P < 0.001) and 12 weeks (8.05 ± 4.59, P < 0.001). Heart rate, systolic, and diastolic blood pressures did not show significant changes during the follow-up in both the study groups. Thirteen patients developed ADRs such as dry mouth (four patients) and constipation (nine patients) in the solifenacin group. No ADRs were noted in the mirabegron group., Conclusion: Mirabegron showed maximum improvement in the OAB-V8 scores in patients with OAB syndrome, although the solifenacin group also showed improvement. Adverse effects were less in the mirabegron group when compared to the solifenacin group., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Perspectives in Clinical Research.)

Background: Oncogenic osteomalacia is a rare paraneoplastic association of Phosphaturic mesenchymal tumor (PMT) secreting excessive levels of a PTH like substance. They usually remain undiagnosed and patients suffer for years. The rarity of this tumor and its non-specific clinical presentations poses great challenge to the treating surgeons. Its management is poorly described in literature. We report two of such rare cases without much diagnostic delay., Case Report: We had 2 cases; A 53-year-old south east Asian male with 6 months of debilitating pain over multiple sites, and another 44-year-old male patient with complaints of low back ache, and pain over both lower and upper limbs for 1.5 years. Both had low serum phosphorus and elevated FGF-23 values, but all other parameters were normal. A PMT was suspected and confirmed on a Ga 68 - DOTATOC scan in both cases, and on complete excision, their symptoms and the altered blood parameters got normalized. Histology was consistent with PMT., Conclusion: Accurate and timely diagnosis of a PMT with non-specific features are extremely challenging, but not without solutions. Even though a tumor of rarity, with the appropriate imaging modalities like Ga 68 - DOTATOC scan, and estimation of FGF-23 and serum phosphorus levels, they can be diagnosed. Once identified, complete removal is often curative within a few months., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The brain-derived neurotrophic factor (BDNF) plays a crucial role during neuronal development as well as during differentiation and synaptogenesis. They are important proteins present in the brain that support neuronal health and protect the neurons from detrimental signals. The results from the present study suggest BDNF expression can be increase up to ~8-fold by treating the neuroblastoma cells SHSY-5Y with an herbal extract of Oroxylum indicum (50 μg/mL) and ~5.5-fold under lipopolysaccharides (LPS)-induced inflammation conditions. The Oroxylum indicum extract (Sabroxy) was standardized to 10% oroxylin A, 6% chrysin, and 15% baicalein. In addition, Sabroxy has shown to possess antioxidant activity that could decrease the damage caused by the exacerbation of radicals during neurodegeneration. A mode of action of over expression of BDNF with and without inflammation is proposed for the Oroxylum indicum extract, where the three major hydroxyflavones exert their effects through additive or synergistic effects via five possible targets including GABA, Adenoside A2A and estrogen receptor bindings, anti-inflammatory effects, and reduced mitochondrial ROS production.

Fluorescent molecules or materials with high photoluminescence quantum yields and stability towards photobleaching are ideally suited for multiplex imaging. Despite complying with such properties, perovskite nanocrystals (Pv-NCs) are rarely used for bioimaging owing to their toxicity and limited stability in aqueous media and towards human physiology. We aim to address these deficiencies by designing core-shell structures with Pv-NCs as the core and surface-engineered silica as the shell (SiO 2 @Pv-NCs) since silica is recognized as a biologically benign carrier material and is known to be excreted through urine. The post-grafting methodology is adopted for developing [SiO 2 @Pv-NCs]tpm and [SiO 2 @Pv-NCs]tsy (tpm: triphenylphosphonium ion, tsy: tosylsulfonamide) for specific imaging of mitochondria and endoplasmic reticulum (ER) of the live HeLa cell, respectively. A subtle difference in their average fluorescence decay times ([SiO 2 @Pv-NCs]tpm: tpm τ av = 3.1 ns and [SiO 2 @Pv-NCs]tsy: tsy τ av = 2.1 ns) is used for demonstrating a rare example of perovskite nanocrystals in fluorescence lifetime multiplex imaging., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Nevus sebaceous (NS) is a rare congenital skin lesion affecting approximately 0.3% of all newborns. Although benign, NS lesions can harbor malignant secondary tumors. The published rate of development of these malignant tumors varies. This meta-analysis aimed to identify the rate of malignant and benign secondary neoplasms occurring in NS., Methods: A literature search was conducted using PubMed, Embase, and Web of Science from inception to April 2023. Eligible studies reported incidence or risk of secondary neoplasms in patients with NS. Two independent reviewers screened studies, extracted data, and assessed the quality of included studies. The primary outcome was the pooled incidence of secondary neoplasms. Studies with sample sizes greater than 50 patients were eligible for meta-analysis using the random-effects model., Results: Twenty-eight studies were identified, 22 of which were eligible for meta-analysis. The overall rate of secondary neoplasms was 12.8% (95% confidence interval [Cl], 9.2%-17.6%). The rates of development of malignant and benign tumors were 2.4% (95% CI, 1.4%-4.1%) and 10.3% (95% CI, 7.5%-13.9%), respectively. The rate of development of basal cell carcinoma was 1.7% (95% CI, 0.9%-3.2%), whereas the rate of the development of syringocystadenoma papilliferum was 3.6% (95% CI, 2.5%-5.3%) and that if trichoblastoma was 2.6% (95% CI, 1.7%-3.8%)., Conclusions: Although the rate of development of malignant tumors within a primary NS lesion is low, it is not negligible. Prophylactic early excision remains a viable approach to prevent secondary malignant neoplasms, address cosmetic and functional complications, and preempt the need for complex reconstruction in the future. We propose that resection of NS lesions in childhood remains a reasonable first-line option in the appropriate patient keeping in mind that it may leave an undesirable scar., Competing Interests: Conflicts of interest and sources of funding: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is conflicting data on whether clot retrieved from mechanical thrombectomy can predict stroke etiology or the success of recanalization. We aimed to analyse the relation between thrombus histology and stroke aetiology as well as recanalization., Methodology: Histopathological analysis of clots retrieved from patients with acute ischemic stroke and large vessel occlusion was done. Quantification of the amount of fibrin, red blood cells(RBC), platelets and white blood cells (WBC) in the clots were done. The clinical, imaging data and recanalization parameters were collected. The correlation between clot composition and stroke etiology as well as recanalization were analysed., Results: Of the 77 patients, the mean age was 58. 67 ± 12.96 years. The stroke etiology were cardioembolism 44(57.1 %), large artery atherosclerosis 13(16.8 %), other determined aetiology 4(5.1 %) and undetermined in 16(20.7 %) patients. There was no significant correlation between the proportions of RBC-rich, platelet-rich and fibrin-rich thrombi and the stroke etiology. The susceptibility vessel sign was associated with RBC-rich clot(92.3 % vs 7.7 %, p = .03). All RBC-rich clots(100 %) had good recanalization(p = .05). Platelet-rich clots needed less number of passes(64.7 % vs 35.3 %, p = .006) and reduced groin puncture to recanalization time(87.9 % vs 12.1 %, p = .033). WBC-rich clots required lesser number of passes(57.5 % vs 42.5 %, P = .044). In multivariate analysis, WBC-rich clots (OR 0.230, CI 0.07-0.78, p = .018) showed an independent association with reduced recanalization attempts, while platelet-rich clots showed reduced recanalization time(OR 0.09, CI 0.01-0.63, p = .016)., Conclusion: There was no correlation between thrombus histology and the etiological stroke subtype. However, clot composition predicted the degree of recanalization and number of passes., 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 Ltd. All rights reserved.)

Introduction and Objectives: OSAKA regimen is a novel bladder preservation therapy involving balloon-occluded selective arterial infusion of radio-sensitizing chemotherapeutic agent with concurrent hemodialysis (HD), followed by radiation therapy. Objectives are to study the feasibility of this novel regimen in patients with advanced cancer bladder (Ca Bladder)., Methods: Two patients having advanced Ca Bladder with cisplatin ineligibility and poor performance status were managed with OSAKA regimen. Patients undergo super selective catheterisation of the anterior division of the internal iliac artery, followed by concurrent instillation of cisplatin (100 mg) via microcatheters and hemodialysis. Within 72 h, definitive radiation therapy is given. Image-guided radiation therapy (IGRT) with Helical Tomo using an Accuracy Radixact Tomography machine was used. 60 Gray/30 fractions is given to the bladder and nodes (50 Gray to bladder and nodes plus margin, with a boost of 10 Gray to bladder plus margin). Response is monitored by 3 monthly fluorodeoxyglucose positron emission tomography (FDG PET) imaging., Results: Our first patient tolerated the procedure well and showed a complete response at 3 months of FDG PET imaging, but unfortunately, 1 year of FDG PET showed bony metastases, and the patient was managed accordingly. Our second patient also tolerated the regimen well, showed a complete response at 3 and 12 months of FDG PET imaging, and is under follow-up., Conclusions: The OSAKA regimen, as a bladder preservation strategy, is feasible and safe in selective advanced Ca Bladder patients., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning., Methodology: Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) days and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer., Results: A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group., Conclusion: Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This case report presents an uncommon long-term complication of external fixator application to distal radius fracture. Despite an initial uneventful fracture healing, the patient presented with Brodie's abscess with Staphylococcus aureus osteomyelitis at the previous pin site 17 years later. A diagnosis of late-onset osteomyelitis, as a manifestation of quiescence chronic osteomyelitis, was made., (© 2024 Society for Indian Hand Surgery and Micro Surgeons. Published by Elsevier B.V. All rights reserved.)

Since the COVID-19 pandemic, masks have become far more widely used by doctors and are now commonplace in the hospital, with many professionals still wearing them for extended amounts of time. Emerging literature describing numerous mask-related difficulties prompted the authors to conduct a study aimed at assessing the self-perceived impact on voices of teaching doctors due to facial protective gear. In this study carried out from October 2021 to March 2022, data was gathered from 170 pre-, para-, and clinical professionals who were involved in offline teaching. Over half of teaching medical professionals were found to be vocally fatigued. Pre and para-clinical professionals have greater vocal tiredness and avoidance than clinical doctors ( p  = 0.016). The type of mask used does not make a significant difference in degree of vocal fatigue. Individuals with lingering respiratory difficulties following COVID-19 were significantly more vocally fatigued than their recovered peers (p value for tiredness and avoidance = 0.010). Thus, teaching doctors are at risk of impaired quality of life due to vocal fatigue. Further research on vocal habits and rest practices in the study population may help identify the most effective interventions., Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04350-8., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background  The COVID-19 pandemic has been difficult for all healthcare providers. Nurses in Indian hospitals are at risk for mental health consequences of COVID-19-related stress. The study aimed to evaluate the mental health responses of Indian nurses working during the COVID-19 pandemic.  Method The study was carried out during the COVID-19 pandemic from November 2020 to February 2021. Frontline nurses (n=387) working in both government and private sectors were recruited from four hospital centers across Mangalore, India. Nurses were selected based on specific inclusion criteria, including active duty within wards and intensive care units designated for COVID-19 care or suspected cases of SARS-CoV-2 infection. Recruitment and data collection were facilitated by medical residents using a mix of physical and electronic survey methods. Results Nurses within the private sector with low personal protective equipment (PPE) security experienced heightened anxiety. Somatic symptoms were incrementally related to mental health depending on the workplace setting; private sector staff reported greater depression symptoms compared to those in government-run hospitals. Self-efficacy buffered against depression outcomes only in nurses within the private sector working within non-COVID units. Conclusions This study's findings showed differential responses to the stress of COVID-19 based on the setting. Future studies should further explore the factors associated with such differences. Somatic symptoms can be indicators of mental health adversity. Early detection and supportive interventions need to be taken into account., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sreedharan et al.)

Introduction: The goal in open tibial fracture management is to achieve a united tibia in an extremity that allows pain free mobilization. The objective of this study was to assess factors that lead to this functional outcome in lower limb reconstruction, from a plastic surgical perspective., Materials and Methods: The Plastic and Reconstructive Surgery lower limb database at a tertiary trauma hospital was searched for open tibial injuries from February 2015 to March 2020. The nature and severity of injury, timing and details of all operations including reconstructions were collected prospectively. Mobility including gait aids, pain, and complications were retrospectively collected. Union was assessed in two ways, depending on fracture location. Metaphyseal and diaphyseal tibial fractures were provided mRUST scores (union defined as RUST > 13) and epiphyseal tibial fractures were categorically classified as "united" or "non-union" by two independent radiologists., Results: During the five-year study period there were 148 open leg injuries in the database. Twenty-one patients underwent a primary amputation due to severity of their initial injury. One hundred patients underwent primary limb salvage. Sixty-one patients in the limb salvage group achieved primary tibial union with a mean follow-up time of 19.4 months post injury. Twenty-three additional patients were confirmed to subsequently unite. Patient who achieved union were more likely to mobilise without gait aids., Discussion: In this study definitive external fixation and soft tissue infection were both associated with higher rates of non-union. Longer times to soft tissue reconstruction was not associated with an increase in acute soft tissue complications. More importantly bone union, pain and mobility did not decline. After undertaking a primary limb salvage pathway for 100 patients, the ultimate tibial fracture union rate was 84% and the confirmed ambulation rate was 96%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Sreedharan, Bruscino-Raiola, Lew, Ling and Ferris.)

Introduction: The use of diagnostic imaging services is increasing worldwide. This has important impacts on healthcare resource allocation and potential risks to the population. This study aimed to quantify trends in medical imaging in Australia over the past two decades., Methods: Data were extracted from the Australian Medicare Benefits Schedule (MBS) between 2000 and 2021. Simple linear regression analyses were performed to assess changes in absolute utilisation and utilisation rate per 100,000 population of total imaging services as well as by each imaging modality. Logistic regression analysis was performed to assess changes in total imaging services as a proportion of total Medicare services over time. Chi-squared test was used to assess for change in modality composition of imaging services., Results: There were 436,255,500 imaging studies performed between 2000 and 2021. The absolute utilisation of total imaging services increased annually by an average of 864,404 (95% CI: 808,235-920,573, p < 0.001). For each consecutive year, the proportion of total Medicare services attributed to total imaging services increased by 0.01% (95% CI: 0.01-0.01, p < 0.01). There was also a statistically significant increase in the utilisation rates of imaging services per 100,000 population for each imaging modality. The number of imaging services per radiologist increased on average by 74 (95% CI: 26-122, p < 0.05) annually., Conclusion: The utilisation of diagnostic imaging services has increased in Australia between 2000 and 2021, outpacing the population growth, total healthcare services, and the radiologist workforce., (© 2023 Royal Australian and New Zealand College of Radiologists.)

MicroRNAs (miRNAs) are small noncoding epigenetic regulators that exert critical significance by influencing target mRNAs and governing gene expression patterns and cellular signaling pathways. miRNAs play a pivotal role in a wide array of biological processes, including cell differentiation, proliferation, and survival. Numerous miRNAs contribute to tumorigenesis and cancer progression by promoting tumor growth, angiogenesis, invasion, and immune evasion, while others exert tumor suppressive effects. From a clinical perspective, it has been demonstrated that numerous miRNAs are related to the prognosis in acute myeloid leukemia (AML) patients. They hold the potential to be utilized as biomarkers, aiding in improved treatment decision-making. Moreover, a number of preclinical investigations have offered compelling evidence to create novel treatment approaches that target miRNAs in AML. This review highlights the clinical significance of miRNAs in the diagnosis, prognosis, and treatment response of adult patients with AML., (© 2023 John Wiley & Sons Ltd.)

Aim: The objective of this study was to identify the clinical epidemiology and medical cost of stings and bites at a tertiary care hospital in South India., Subjects and Methods: The medical records of hospitalized patients in the tertiary care unit between 2016 and 2020 with the history of either being stung or bitten by insects were reviewed retrospectively. The patient's demographic details, clinical symptoms, treatment chart, expenditure details, and outcomes were collected in pre-structured case report forms. The data were analyzed using SPSS Version 20.0., Results: A total of 66 patients were enrolled, with a mean age of 45.86 ± 23.37 years. The majority of the incidence was due to bee stings (61%). Anaphylaxis was reported in 38% of the cases, followed by acute kidney injury (10.6%). The cost of hospitalization was found to be higher for spider bites at 896.73 ± 1414.95 USD, followed by wasp stings at 989.81 ± 1185.57 USD. In patients with complications, the average cost of stings and bites was 438.81 ± 685.81 USD. Most of the patients received antibiotics (75.8%), followed by steroids (62.1%)., Conclusion: Stings and bite injuries may appear harmless initially, but they can cause severe complications in unidentified cases and for those who do not seek urgent medical attention. Antibiotics and corticosteroids can help in the management of envenomation., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Impairment of synaptic plasticity along with the formation of amyloid-β (Aβ) plaques and tau-protein neurofibrillary tangles have been associated with Alzheimer's disease (AD). Earlier studies with rat and mouse hippocampal slices have revealed the association of AD with the absence of synthesis of memory related proteins leading to impairment in cognitive functions. The role of hydrogen sulfide (H2S), a gaseous neurotransmitter, has been gaining attention as a neuroprotective agent. However, its role in AD-like conditions has not been studied so far., Objective: To study the neuroprotective role of H2S in AD conditions using rat hippocampal slices and the organic molecule GYY4137, a slow releasing H2S donor., Methods: Electrophysiological recordings were carried out in rat hippocampal slices to look into the impairment of LTP, a cellular correlate of memory. The Aβ42 peptide was bath-applied to mimic AD-like conditions and checked for both late-LTP and synaptic tagging and capture (STC) mechanisms of the synapses. GYY4137 was applied to look into its neuroprotective role at different stages during the recording of fEPSP., Results: There has been a steady decline in the plasticity properties of the synapses, in the form of late-LTP and STC, after the application of Aβ42 peptide in the hippocampal slices. However, application of GYY4137 rescued these conditions in vitro., Conclusions: GYY4137, with its slow release of H2S, could possibly act as a therapeutic agent in cognitive dysfunctions of the brain, mainly AD.

Iron-sulfur (Fe-S) biogenesis requires multiprotein assembly systems, SUF and ISC, in most prokaryotes. M. tuberculosis ( Mtb ) encodes a complete SUF system, the depletion of which was bactericidal. The ISC operon is truncated to a single gene iscS (cysteine desulfurase), whose function remains uncertain. Here, we show that Mtb Δ iscS is bioenergetically deficient and hypersensitive to oxidative stress, antibiotics, and hypoxia. Mtb Δ iscS resisted killing by nitric oxide (NO). RNA sequencing indicates that IscS is important for expressing regulons of DosR and Fe-S-containing transcription factors, WhiB3 and SufR. Unlike wild-type Mtb , Mtb Δ iscS could not enter a stable persistent state, continued replicating in mice, and showed hypervirulence. The suf operon was overexpressed in Mtb Δ iscS during infection in a NO-dependent manner. Suppressing suf expression in Mtb Δ iscS either by CRISPR interference or upon infection in inducible NO-deficient mice arrests hypervirulence. Together, Mtb redesigned the ISC system to "fine-tune" the expression of SUF machinery for establishing persistence without causing detrimental disease in the host.

Upon water loss, some organisms pause their life cycles and escape death. While widespread in microbes, this is less common in animals. Aedes mosquitoes are vectors for viral diseases. Aedes eggs can survive dry environments, but molecular and cellular principles enabling egg survival through desiccation remain unknown. In this report, we find that Aedes aegypti eggs, in contrast to Anopheles stephensi, survive desiccation by acquiring desiccation tolerance at a late developmental stage. We uncover unique proteome and metabolic state changes in Aedes embryos during desiccation that reflect reduced central carbon metabolism, rewiring towards polyamine production, and enhanced lipid utilisation for energy and polyamine synthesis. Using inhibitors targeting these processes in blood-fed mosquitoes that lay eggs, we infer a two-step process of desiccation tolerance in Aedes eggs. The metabolic rewiring towards lipid breakdown and dependent polyamine accumulation confers resistance to desiccation. Furthermore, rapid lipid breakdown is required to fuel energetic requirements upon water reentry to enable larval hatching and survival upon rehydration. This study is fundamental to understanding Aedes embryo survival and in controlling the spread of these mosquitoes., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2023 Prasad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To determine whether preeclampsia and gestational diabetes mellitus is a risk factor for cochlear damage and sensorineural hearing impairment in infants., Materials and Methods: Longitudinal study was conducted in 2 tertiary referral centers. 1068 neonates were included, who were born to preeclampsia, gestational diabetes mellitus, and healthy mothers. The hearing evaluation was done using DPOAE on day 2 and for those who failed the initial DPOAE on day 2, underwent repeat DPOAE on day 15, ABR was done on day 30 if repeat DPOAE was Refer. The results were compared between the groups and analyzed., Results: On initial DPOAE, bilateral ear absent DPOAE rates were 19.5%, 15.8%, and 3.5% among preeclampsia, Gestational Diabetes Mellitus (GDM), control groups respectively. The difference was statistically significant ( P  < .001). Also it was noted that absent DPOAE was significantly high at low and mid frequencies (1000, 2000, 3000, and 4000 Hz) in bilateral ear. However the difference in repeat DPOAE among the groups were not significant (Right ear P  = .17, Left ear P  = .31). Infants who failed repeat DPOAE test underwent ABR test in which 3 of GDM group, 2 infants of preeclampsia group and 1 infant of control group had absent ABR test., Conclusion: This study reveals that GDM and preeclampsia showed remarkable association of hearing loss at lower and mid frequencies which was transient. The prevalence of absent DPOAE was corresponding to the severity of the maternal conditions under the study.

Introduction: Drug-resistant fungal infections in chronic wounds represent a major clinical challenge to clinicians. Fungal infections delay wound healing by prolonging inflammation and encouraging biofilm formation, which protects microbes against host defenses and anti-infective medications. As such, interventions that prevent and control nosocomial fungal infections without interfering with the wound healing process are increasingly required. Although conventional antiseptics can effectively exert fungicidal effects, they also have adverse effects on human cells. SOS is a well-known bactericidal agent that enhances the wound healing process, especially for chronic wounds. However, few studies have evaluated the antimicrobial activity of SOS on fungi., Objective: The objective of this study was to evaluate whether SOS exerts fungicidal activities against common fungal species., Materials and Methods: The efficacy of SOS was tested against 6 fungal species (Candida albicans, Candida auris, Candida tropicalis, Candida parapsilosis, Sporothrix schenckii, Trichophyton mentagrophytes) using an in vitro time-kill assay., Results: SOS achieved 99.9999% reduction of all tested fungi within 1 minute of exposure., Conclusions: This study shows that SOS may be an effective tool for the prevention and control of fungal infections.

Age-induced impairments in learning and memory are in part caused by changes to hippocampal synaptic plasticity during aging. The p75 neurotrophin receptor (p75 NTR ) and mechanistic target of rapamycin (mTOR) are implicated in synaptic plasticity processes. mTOR is also well known for its involvement in aging. Recently, p75 NTR and mTOR were shown to be mechanistically linked, and that p75 NTR mediates age-induced impairment of hippocampal synaptic plasticity. Yet the consequences of p75 NTR -mTOR interaction on hippocampal synaptic plasticity, and the role of mTOR in age-induced cognitive decline, are unclear. In this study, we utilize field electrophysiology to study the effects of mTOR inhibition and activation on long-term potentiation (LTP) in male young and aged wild-type (WT) mice. We then repeated the experiments on p75 NTR knockout mice. The results demonstrate that mTOR inhibition blocks late-LTP in young WT mice but rescues age-related late-LTP impairment in aged WT mice. mTOR activation suppresses late-LTP in aged WT mice while lacking observable effects on young WT mice. These effects were not observed in p75 NTR knockout mice. These results demonstrate that the role of mTOR in hippocampal synaptic plasticity is distinct between young and aged mice. Such effects could be explained by differing sensitivity of young and aged hippocampal neurons to changes in protein synthesis or autophagic activity levels. Additionally, elevated mTOR in the aged hippocampus could cause excessive mTOR signaling, which is worsened by activation and alleviated by inhibition. Further research on mTOR and p75 NTR may prove useful for advancing understanding and, ultimately, mitigation of age-induced cognitive decline., (© 2023 Federation of American Societies for Experimental Biology.)

The chemical profiling of phenolic and terpenoid compounds in whole cardamom, skin, and seeds ( Elettaria cardamomum (L.) Maton) showed 11 phenolics and 16 terpenoids, many of which are reported for the first time. Herein, we report the anti-inflammatory properties of a methanolic extract of whole cardamom in colon and macrophage cells stimulated with an inflammatory bacteria lipopolysaccharide (LPS). The results show that cardamom extracts lowered the expression of pro-inflammatory genes NFkβ , TNFα , IL-6 , and COX2 in colon cells by reducing reactive oxygen species (ROS) while not affecting LXRα . In macrophages, cardamom extracts lowered the expression of pro-inflammatory genes NFkβ , TNFα , IL-6 , and COX2 and decreased NO levels through a reduction in ROS and enhanced gene expression of nuclear receptors LXRα and PPARγ. The cardamom extracts in a range of 200-800 μg/mL did not show toxicity effects in colon or macrophage cells. The whole-cardamom methanolic extracts contained high levels of phenolics compounds (e.g., protocatechuic acid, caffeic acid, syringic acid, and 5-O-caffeoylquinic acid, among others) and are likely responsible for the anti-inflammatory and multifunctional effects observed in this study. The generated information suggests that cardamom may play a protective role against low-grade inflammation that can be the basis of future in vivo studies using mice models of inflammation and associated chronic diseases.

Multi-modular enzyme complexes known as non-ribosomal peptide synthetases (NRPSs) and polyketide synthetases (PKSs) have been widely reported in bacteria that produce secondary bioactive metabolites such as non-ribosomal peptides (NRPs) and polyketides (PKs), respectively. These NRPS/PKS pathways contribute to synthesizing several antibiotics, such as vancomycin, rifamycin, and bleomycin, which are vital in human medicine. The present study aimed to isolate gut-associated bacteria from mud crab Scylla serrata , and detect NRPS and PKS gene clusters associated with it. This study included 36 bacterial isolates from five mud crab gut samples. Biosynthetic gene clusters (NRPS and PKS), were detected by PCR using degenerative primers specific to these genes. Three isolates (FKP2-4, FKP4-1, and FKP2-16) were positive for NRPS and two for PKS (FKP2-4 and FKP4-1) genes. The isolates were subjected to 16S rRNA gene amplification and sequenced. In silico analysis of the sequences using the Basic Local Alignment Search Tool (BLAST) identified the isolates FKP2-4, FKP4-1, and FKP2-16 as Acinetobacter variabilis, Vagococcus fluvialis, and Staphylococcus arlettae , respectively, after comparing with the existing sequences available in the National Center for Biotechnology Information (NCBI) database. Compared to the control, it was observed that these isolates exhibited intriguing antagonistic activities against Escherichia coli and Staphylococcus aureus . However, these isolates failed to show significant activity against Candida albicans . Exopolysaccharide production by the isolated organisms was tested using Zobell marine agar (ZMA) with 5% sucrose, but none of the colonies were mucoid or slimy., Competing Interests: 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. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (© 2023 The Author(s).)

The synthesis of a new heterodinuclear Re I Ru II metallointercalator containing Ru II (dppz) and Re I (dppn) moieties is reported. Cell-free studies reveal that the complex has similar photophysical properties to its homoleptic M(dppz) analogue and it also binds to DNA with a similar affinity. However, the newly reported complex has very different in-cell properties to its parent. In complete contrast to the homoleptic system, the Ru II (dppz)/Re I (dppn) complex is not intrinsically cytotoxic but displays appreciable phototoxic, despite both complexes displaying very similar quantum yields for singlet oxygen sensitization. Optical microscopy suggests that the reason for these contrasting biological effects is that whereas the homoleptic complex localises in the nuclei of cells, the Ru II (dppz)/Re I (dppn) complex preferentially accumulates in mitochondria. These observations illustrate how even small structural changes in metal based therapeutic leads can modulate their mechanism of action., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The hippocampal CA2 region has received greater attention in recent years due to its fundamental role in social memory and hippocampus-dependent memory processing. Unlike entorhinal cortical inputs, the Schaffer collateral inputs to CA2 do not support activity-dependent long-term potentiation (LTP), which serves as the basis for long-term memories. This LTP-resistant zone also expresses genes that restrict plasticity. With the aim of exploring social interaction and sociability in rats that were subjected to juvenile stress, we addressed questions about how the neural circuitry is altered and its effects on social behavior. Although there was induction of LTP in both Schaffer collateral and entorhinal cortical pathways in juvenile-stressed rats, LTP declined in both pathways after 2-3 h. Moreover, exogenous bath application of substance P, a neuropeptide that resulted in slow onset long-lasting potentiation in control animals while it failed to induce LTP in juvenile-stressed rats. Our study reveals that juvenile-stressed rats show behavioral and cellular abnormalities with a long-lasting impact in adulthood., (© 2023 The Authors. Hippocampus published by Wiley Periodicals LLC.)

Purpose: E-cigarettes have become increasingly popular devices used to consume nicotine in recent years. There is a growing body of evidence regarding the risk of spontaneous explosion of these devices causing burn and projectile injuries. The primary purpose of this review was to summarize all injuries to the oral and maxillofacial region secondary to explosion of e-cigarettes. The secondary purpose was to propose an initial management algorithm for such injuries based on the findings in the literature. This review also aims to test the hypothesis that e-cigarette explosive injuries to the oral region were associated with an increased risk of intubation and surgery and examine whether any other injury pattern was associated with an increased risk of intubation or surgery., Methods: A cohort study based on identifying cases in the literature was conducted to summarize injuries to the oral and maxillofacial region and examine the associations between injury types and location and management. A literature search of the major biomedical databases was conducted in September 2022 using terms such as e-cigarette, explosion, blast, trauma, and burn, among others, which yielded 922 studies. Nonclinical studies, review articles, and studies without injuries to the facial region were excluded. Study subjects were recorded for demographics, device characteristics, injury mechanism, injury location, management, and complications. Chi-squared analysis was used to determine if the predictor variables of type of injury (burn or projectile) and its associated location (ocular, facial, or intraoral for burns and facial thirds for projectile) were associated with the outcomes of intubation and surgical management. The collected data were then used as a guide to propose an initial management algorithm for these injuries., Results: Twenty eight studies, including 20 case reports and 8 case series met the inclusion criteria. A total of 32 explosions of e-cigarettes to 32 patients caused 105 recorded injuries to the facial region. Projectile injuries made up 73.3% (n = 77) of all facial injuries, while burn injuries made up of 26.7% (n = 28). There were 14 (43.8%) patients who suffered both projectile and burn injuries. Burn injuries mostly involved the face (64.3%, n = 18), oral cavity (25%, n = 7), and eye (10.7%, n = 7). The majority (81.8%, n = 63) of projectile injuries occurred in the lower facial third. There were 20 (62.5%) patients who suffered a bone or tooth fracture. Management of injuries involved surgery in 62.5% (n = 20) of patients, which included open reduction and internal fixation of fractures, dental extraction, bone and skin grafts, and ocular surgery. A complication rate of 44.4% (n = 8) was observed across studies that reported on follow-up. There was no statistically significant association between explosive injury to the oral region and intubation or surgical management. There was also no other statistically significant association between any other injury type and location with intubation or surgical management., Conclusions: E-cigarettes are at risk for spontaneous combustion that can cause serious oral and maxillofacial injuries, particularly to the lower facial third and commonly requiring surgical management. Safety of these devices should be improved through increased user education and regulation., (Copyright © 2023 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss and cognitive decline. Synaptic impairment is one of the first events to occur in the progression of this disease. Synaptic plasticity and cellular association of various plastic events have been shown to be affected in AD models. Nogo-A, a well-known axonal growth inhibitor with a recently discovered role as a plasticity suppressor, and its main receptor Nogo-66 receptor 1 (NGR1) have been found to be overexpressed in the hippocampus of Alzheimer's patients. However, the role of Nogo-A and its receptor in the pathology of AD is still widely unknown. In this work we set out to investigate whether Nogo-A is working as a plasticity suppressor in AD. Our results show that inhibition of the Nogo-A pathway via the Nogo-R antibody in an Alzheimer's mouse model, APP/PS1, leads to the restoration of both synaptic plasticity and associativity in a protein synthesis and NMDR-dependent manner. We also show that inhibition of the p75 NTR pathway, which is strongly associated with NGR1, restores synaptic plasticity as well. Mechanistically, we propose that the restoration of synaptic plasticity in APP/PS1 via inhibition of the Nogo-A pathway is due to the modulation of the RhoA-ROCK2 pathway and increase in plasticity related proteins. Our study identifies Nogo-A as a plasticity suppressor in AD models hence targeting Nogo-A could be a promising strategy to understanding AD pathology., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We recently nominated cytokine signaling through the Janus-kinase-signal transducer and activator of transcription (JAK/STAT) pathway as a potential AD drug target. As hydroxychloroquine (HCQ) has recently been shown to inactivate STAT3, we hypothesized that it may impact AD pathogenesis and risk. Among 109,124 rheumatoid arthritis patients from routine clinical care, HCQ initiation was associated with a lower risk of incident AD compared to methotrexate initiation across 4 alternative analyses schemes addressing specific types of biases including informative censoring, reverse causality, and outcome misclassification (hazard ratio [95% confidence interval] of 0.92 [0.83-1.00], 0.87 [0.81-0.93], 0.84 [0.76-0.93], and 0.87 [0.75-1.01]). We additionally show that HCQ exerts dose-dependent effects on late long-term potentiation (LTP) and rescues impaired hippocampal synaptic plasticity prior to significant accumulation of amyloid plaques and neurodegeneration in APP/PS1 mice. Additionally, HCQ treatment enhances microglial clearance of Aβ 1-42, lowers neuroinflammation, and reduces tau phosphorylation in cell culture-based phenotypic assays. Finally, we show that HCQ inactivates STAT3 in microglia, neurons, and astrocytes suggesting a plausible mechanism associated with its observed effects on AD pathogenesis. HCQ, a relatively safe and inexpensive drug in current use may be a promising disease-modifying AD treatment. This hypothesis merits testing through adequately powered clinical trials in at-risk individuals during preclinical stages of disease progression., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Problem Considered: Coronavirus disease(COVID-19) outbroke towards the end of December 2019 in China, soon it started spreading rapidly to various countries leading to an outburst of pandemic. Due to the restrictions imposed to control the spread of the infection, globally the manufacturing, import and export of medicine and the healthcare services to patients with chronic illness had been affected. This study aimed to explore the perspectives of the pharmacists on the medicine supply chain for patients with chronic diseases during COVID-19 pandemic in India., Methods: This study is a prospective, qualitative research involving telephonic, semi-structured in-depth interviews. An interview guide for pharmacists was prepared and validated using "Interview Protocol Refinement" method. Purposive sampling method was used to recruit the pharmacists; a telephonic oral consent was obtained. The interview session was audio recorded and the recordings were transcribed verbatim. Further, transcripts were validated and later analysed using NVivo software., Results: A total of 8 participants were interviewed during our study. Thematic analysis of the transcripts resulted in seven main themes. The study showed that there was deficiency in medicine supply during the COVID-19 pandemic and the pharmacists faced several challenges in procuring and storing the medication, arranging for unavailable medicines, medication dispensing and provision of the services such as medicine delivery, patient counselling. There was also scarcity of manpower leading to extra workload and working overtime., Conclusion: Uninterrupted supply of essential medicine is the backbone of health care system. An effective plan and appropriate strategies are vital to combat such future emergencies., Competing Interests: The authors declare no conflicts of interest to disclose., (© 2023 Published by Elsevier B.V. on behalf of INDIACLEN.)

Objective: Most Deep Learning (DL) methods for the classification of functional Near-Infrared Spectroscopy (fNIRS) signals do so without explaining which features contribute to the classification of a task or imagery. An explainable artificial intelligence (xAI) system that can decompose the Deep Learning mode's output onto the input variables for fNIRS signals is described here. Approach: We propose an xAI-fNIRS system that consists of a classification module and an explanation module. The classification module consists of two separately trained sliding window-based classifiers, namely, (i) 1-D Convolutional Neural Network (CNN); and (ii) Long Short-Term Memory (LSTM). The explanation module uses SHAP (SHapley Additive exPlanations) to explain the CNN model's output in terms of the model's input. Main results: We observed that the classification module was able to classify two types of datasets: (a) Motor task (MT), acquired from three subjects; and (b) Motor imagery (MI), acquired from 29 subjects, with an accuracy of over 96% for both CNN and LSTM models. The explanation module was able to identify the channels contributing the most to the classification of MI or MT and therefore identify the channel locations and whether they correspond to oxy- or deoxy-hemoglobin levels in those locations. Significance: The xAI-fNIRS system can distinguish between the brain states related to overt and covert motor imagery from fNIRS signals with high classification accuracy and is able to explain the signal features that discriminate between the brain states of interest., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shibu, Sreedharan, Arun, Kesavadas and Sitaram.)

Background: Malignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site., Methods: Here we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next-generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies., Results: A large fraction of common integration sites contained genes that have been dysregulated or misexpressed in glioma. Others overlapped with loci identified in previous glioma-related forward genetic screens, but several novel putative cancer-causing genes were also found. Integrating retroviral tagging and clinical data, Ppfibp1 was highlighted as a frequently tagged novel glioma-causing gene. Retroviral integrations into the locus resulted in Ppfibp1 upregulation, and Ppfibp1-tagged cells generated tumors with shorter latency on orthotopic transplantation. In human gliomas, increased PPFIBP1 expression was significantly linked to poor prognosis and PDGF treatment resistance., Conclusions: Altogether, the current study has demonstrated a novel approach to tagging glioma genes via forward genetics, validating previous results, and identifying PPFIBP1 as a putative oncogene in gliomagenesis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

The amygdala is known to modulate hippocampal synaptic plasticity. One role could be an immediate effect of basolateral amygdala (BLA) in priming synaptic plasticity in the hippocampus. Another role could be through associative synaptic co-operation and competition that triggers events involved in the maintenance of synaptic potentiation. We present evidence that the timing and activity level of BLA stimulation are important factors for the induction and maintenance of long-term potentiation (LTP) in ventral hippocampal area CA1. A 100 Hz BLA co-stimulation facilitated the induction of LTP, whereas 200 Hz co-stimulation attenuated induction. A 100 Hz BLA co-stimulation also caused enhanced persistence, sufficient to prevent synaptic competition. This maintenance effect is likely through translational mechanisms, as mRNA expression of primary response genes was unaffected, whereas protein level of plasticity-related products was increased. Further understanding of the neural mechanisms of amygdala modulation on hippocampus could provide insights into the mechanisms of emotional disorders., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The integration of nanomaterials (NMs) into an ever-expanding number of daily used products has proven to be highly desirable in numerous industries and applications. Unfortunately, the same "nano" specific physicochemical properties, which make these materials attractive, may also contribute to hazards for individuals exposed to these materials. In 2021, it was estimated that 7 out of 10 deaths globally were accredited to chronic diseases, such as chronic liver disease, asthma, and cardiovascular-related illnesses. Crucially, it is also understood that a significant proportion of global populace numbering in the billions are currently living with a range of chronic undiagnosed health conditions. Due to the significant number of individuals affected, it is important that people suffering from chronic disease also be considered and incorporated in NM hazard assessment strategies. This review examined and analyzed the literature that focused on NM-induced adverse health effects in models which are representative of individuals exhibiting pre-existing medical conditions with focus on the pulmonary, cardiovascular, hepatic, gastrointestinal, and central nervous systems. The overall objective of this review was to outline available data, highlighting the important role of pre-existing disease in NM-induced toxicity with the aim of establishing a weight of evidence approach to inform the public on the potential hazards posed by NMs in both healthy and compromised persons in general population.

Objectives: Insulin degludec (IDeg)/insulin aspart (IAsp; IDegAsp) is a co-formulation of 70% IDeg and 30% IAsp. According to several randomized controlled trials, IDegAsp is effective and safe for patients with type 2 diabetes mellitus (T2DM). A subgroup analysis of the ARISE study was conducted to explore the safety and efficacy of IDegAsp among Malaysian patients with T2DM in real-world settings., Methodology: ARISE, an open-label, multicenter, non-interventional, prospective study was conducted between August 2019 and December 2020. Adult Malaysian patients with T2DM who were enrolled from 14 sites received IDegAsp as per the local label for 26 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) levels from baseline to end of study (EOS)., Results: Of the 182 patients included in the full analysis set, 159 (87.4%) completed the study. From baseline to EOS, HbA1c (estimated difference [ED]: -1.3% [95% CI: -1.61 to -0.90]) and fasting plasma glucose levels (ED: -1.8 mmol/L [95% CI: -2.49 to -1.13]) were significantly reduced ( p <0.0001). The patient-reported reduced hypoglycemic episodes (overall and nocturnal) during treatment. Overall, 37 adverse events were observed in 23 (12.6%) patients., Conclusion: Switching or initiating IDegAsp treatment resulted in significant improvements in glycemic control and a reduction in hypoglycemic episodes., Competing Interests: All the authors have received honoraria from Novo Nordisk, unrelated to the current manuscript. The primary author is a member of the local advisory board for Novo Nordisk who received research contracts from Novo Nordisk., (© 2023 Journal of the ASEAN Federation of Endocrine Societies.)

Background: COVID-19 has become extremely dangerous manifesting itself in a variety of forms ranging from a simple flu-like illness to death. COVID-19 associated mucormycosis (CAM) is a global threat with diabetes being a major contributor., Objective: This review aims to give a clear picture of the impact of hyperglycemia in CAM along with its management., Methods: Google and Google Scholar were searched and studies that addressed the impact of diabetes in CAM were considered for this review. We also performed a bibliographic search of the specific article to find additional studies., Results: A series of events such as unregulated activation of innate immune system modification, pro-inflammatory M1 macrophages activation, and the depletion of natural killer cell activity is very common in patients with COVID-19. In addition, the exacerbated cytokine syndrome and hyperinflammatory response may elevate the severity of this condition, which further leads to higher mortality. The impaired immune phase which follows provide the niche for increased infection among diabetic patients making them more prone towards developing mucormycosis and associated infections. Early detection, surgical debridement, and appropriate medical treatment with antifungals and hypoglycaemic agents may help control the infection and associated morbidity and mortality. COVID-19 drugs, hypoglycaemic agents, antifungals, and comorbidities have all been associated with adverse side effects and drug interactions., Conclusion: Clinicians should be well aware of this deadly disease and manage COVID-19, diabetes, and mucormycosis through individualized treatment regimens to improve patient outcomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Following an overview of the approaches and techniques used to acheive super-resolution microscopy, this review presents the advantages supplied by nanoparticle based probes for these applications. The various clases of nanoparticles that have been developed toward these goals are then critically described and these discussions are illustrated with a variety of examples from the recent literature.

Objectives: Carotid atherosclerosis accounts for around 20 % of ischemic strokes. Literature on CT angiography [CTA] to study plaque morphology is limited. We studied plaque characteristics of extracranial carotid arteries using CTA to ascertain the high risk features beyond luminal stenosis., Materials and Methods: Retrospective study design, where patients with carotid territory ischemia who underwent CTA from January 2011 till December 2015 were recruited from medical records. CT images were reviewed for plaque characteristics like attenuation, ulceration, plaque thickness and presence of intraluminal thrombus [ILT] along with percentage stenosis., Results: 114 patients with 201 carotids [102 symptomatic and 99 asymptomatic] were reviewed. Mixed density plaques [p = 0.05], ulceration [p = 0.001], ILT [p = 0.004] and higher soft plaque thickness [p < 0.001] were significantly associated with symptomatic carotids whereas calcified plaques were seen in asymptomatic carotids [p = 0.005]. Plaque characteristics were comparable in symptomatic patients with moderate[50-69 %] and severe[70-99 %] stenosis. Multivariate analysis showed that increased soft plaque thickness remained significantly associated with symptomatic carotid. A cut-off value for soft plaque thickness of 2.75 mm could predict symptomatic carotid disease with a sensitivity of 85.2 % and specificity of 68.0 % [Youden's index]. An increase in soft plaque thickness of 4.0 mm significantly predicts change from asymptomatic to symptomatic carotid [p < 0.05]., Conclusions: Of the studied CTA plaque characteristics, soft plaque thickness is an independent predictor of symptomatic disease irrespective of the percentage stenosis. Soft plaque thickness over 2.75 mm and smallest detectable change[4 mm] are new measures to help ascertain the risk of ischemic events in carotid atherosclerotic disease., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest to report., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Schwannomas are tumous that arise from Schwann cells. Schwannoma is one of the differential diagnosis for lateral neck swelling., Objective: In this study, we aim to describe the incidence, presenting clinical features and management of extracranial, non-vestibular schwannomas of head and neck region, along with the review of the literature., Methods: Patients treated at our tertiary care hospital for head and neck schwannomas for the past 15 years were included in the study. A review of literature on the extracranial head and neck schwannoma was also done., Results: Twenty-five cases were assessed in this study. Nineteen cases presented as a neck swelling during the initial evaluation. Vagus nerve was the most common nerve of origin, followed by the cervical sympathetic plexus. A rare presentation arising from brachial plexus C5 nerve root was also encountered. A few rare cases of schwannomas arose from the nasal cavity, paranasal sinuses, and oral cavity. Surgical excision was done in all the cases with histopathology suggestive of schwannoma. The nerve of origin of the tumor was identified in nineteen patients. Among them, 11 (58%) were from the vagus nerve, 7 (37%) from the cervical sympathetic chain, and 1 (4%) from the brachial plexus C5 nerve root., Conclusion: A long-standing unilateral neck mass is the most common presenting complaint in head and neck schwannoma. The diagnosis is mainly based on clinical features and investigations such as imaging. The mainstay of treatment is complete surgical excision. The diagnosis is confirmed on the histopathological study after excision of the lesion. Due to the proximity of the tumor with the involved nerve, palsy may occur. Hence, an accurate preoperative diagnosis of schwannoma is essential., (Copyright © 2021 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Purpose: Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong association with AED-induced severe cutaneous adverse drug reactions., Objective: We aimed to perform a systematic review and meta-analysis to identify, critically evaluate, and synthesize the best possible evidence on HLA-associated AED-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)., Methods: MEDLINE/PubMed, Scopus, and the Cochrane Library were searched for literature from inception up to July 2022. We included case control studies analyzing association between HLA and AED-induced SJS/TEN. We assessed the studies' risk of bias in using Quality of genetic studies (Q-genie) tool. Outcomes focused on association (risk) between HLA and AED-induced SJS/TEN. The estimated risk was presented in the form of odds ratio (OR)., Results: We included 37 studies (51,422 participants; 7027 cases and 44,395 controls). There was a significantly higher risk of Carbamazepine-induced SJS/TEN with HLA-A (OR: 1.50; 95% CI: 1.03 to 2.17), HLA-B (OR: 1.94; 95% CI: 1.45 to 2.58), HLA-C (OR: 7.83; 95% CI: 4.72 to 12.98), and HLA-DRB1 (OR: 2.82; 95% CI: 1.94 to 4.12). Lamotrigine-induced SJS/TEN posed a higher risk with HLA-A (OR: 2.38; 95% CI: 1.26 to 4.46) and HLA-B (OR: 2.79; 95% CI: 1.75 to 4.46). Phenytoin-induced SJS/TEN showed a higher risk with HLA-A (OR: 3.47; 95% CI: 2.17 to 5.56), HLA-B (OR: 1.72; 95% CI: 1.38 to 2.15), and HLA-C (OR: 2.92; 95% CI: 1.77 to 4.83). Phenobarbital-induced SJS/TEN had a higher risk with HLA-A (OR: 6.98; 95% CI: 1.81 to 26.84), HLA-B (OR: 2.40; 95% CI: 1.39 to 4.17), and HLA-C (OR: 3.37; 95% CI: 1.03 to 11.01). Zonisamide-induced SJS/TEN was significantly associated with HLA-A*02:07 (OR: 9.77; 95% CI: 3.07 to 31.1), HLA-B*46:01 (OR: 6.73; 95% CI: 2.12 to 21.36), and HLA-DRB1×08:03 (OR: 3.78; 95% CI: 1.20 to 11.97). All other alleles of HLA were observed to have a non-significant association with AED-induced SJS/TEN. All included studies were of good quality, with a score of >50 and a mean score of 54.96 out of 77., Conclusion: Our study showed a significant association between few variants of HLA alleles and AED-induced SJS/TEN. Evidences from our study could help in population-based studies and in implementation of individualized treatment regimens. These findings could be part of translational research helping in precision therapy., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest to declare. The listed authors are solely responsible for the originality and content of the manuscript. The authors have no relevant affiliations or financial involvements with any organizations or entities with a financial interest in or financial conflict with the subject matter discussed in the manuscript., (Copyright © 2022. Published by Elsevier Ltd.)

A laryngoscopically benign lesion with minimal hoarseness may turn out to be mimickers of malignancy or malignancy itself. Histopathological study is mandatory in such cases to rule out malignancy. A descriptive study of histopathological and laryngoscopic findings of benign laryngeal lesions were studies over a period of 4.5 years. Among the thirty-six patients studied, the mean age of the patients was 42 years. The most common presenting complaint was hoarseness of voice seen in 87.5% of cases. Twelve cases of vocal cord polyps were diagnosed based on clinical, laryngoscopical and histopathological features. Seven cases of vocal cord nodules, presenting with hoarseness of voice and laryngoscopic finding of a small nodular growth over the cord. Nine cases of laryngeal papillomas and papillomatosis showed branching papillae, lined by squamous epithelium with fibrovascular cores. A single case of amyloidosis and four cases of granulomatous lesions suggestive of tuberculosis were studied. One case each of rhabdomyoma and granular cell tumour was reported and confirmed by immunohistochemistry. Rare benign tumours and tumour-like lesions mimicking malignancy on laryngoscopy need histopathological evaluation. It is mandatory to study excised biopsies of the larynx as grossly similar lesions can vary from non-neoplastic to frankly malignant., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2020.)

Objectives: To quantify tumour size and margin shrinkage due to formalin fixation in head and neck cancer specimens and determine its effect on tumour staging and margin clearance., Methods: Tumour specimens were measured immediate post-resection and at 24 hours after fixation. Tumour was measured in 2 dimensions and one margin was measured. Shrinkage was categorised as < 10%, 10-20%, and > 20%. Effect of shrinkage on tumour stage and margin clearance were evaluated., Results: A total of 50 specimens were analysed. The tumour AP (Anterior Posterior) and SI (Superior Inferior) measurements showed significant shrinkage with a mean difference of 22.93% and 21.69% respectively. > 20% shrinkage was noted in 78% of AP and 58% of SI measurements. Margins showed a mean difference of 25.61%. 84% of margins demonstrated > 20% shrinkage. In all, 46.7% of T3 and 23% of T2 tumours pre-fixation were downstaged to T2 and T1, respectively, post-fixation., Conclusions: Formalin fixation alone can be responsible for significant shrinkage of tumour and margin dimensions in head and neck specimens. It is suggested that decisions regarding the treatment plan should be made on clinical staging of primary tumour rather than pathological staging. In addition, post-excision pre-fixation margins should be considered for treatment planning., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background and Objective: Proton Pump Inhibitors (PPIs) reduce gastric acid production and they are indicated for myriad gastrointestinal conditions. Prolonged use of PPI has been linked to the risk of inflammatory bowel disease (IBD) though this fact is not well established. We aimed to conduct a systematic review and meta-analysis to estimate the risk of IBD occurrence with PPI use., Methodology: The databases such as PubMed, Scopus, and Cochrane Library were accessed from inception to December 2020. Additionally, the bibliographic search and a random search in Google, Google Scholar, and ResearchGate were performed to find additional sources. The observational studies estimating the risk of IBD following the use of PPI, published in the English language were considered for this review. The methodological quality of included studies was assessed using the Modified Downs and Black checklist., Results: Eight out of 2038 studies with 157,758 participants were included in this meta-analysis. A significantly higher risk of IBD (adjusted odds ratio [aOR] 2.43; 95% Confidence Interval [CI] 1.18-5.02; P=0.02; n=6) was observed in participants taking PPIs for any indication. Moreover, a significant association was observed between PPI exposure on the different types of IBD such as ulcerative colitis and Crohn's disease together (aOR: 3.60; 95% CI: 1.10-11.74), collagenous colitis (OR: 4.73; 95% CI: 1.99-11.22) and lymphocytic Colitis (OR: 3.77; 95% CI: 2.91-4.87), but not with ulcerative colitis (P=0.47) and microscopic colitis (P=0.07) alone. Similarly, a significant association was observed among Europeans (aOR: 3.98; 95% CI: 2.36-6.71), but not with North American (aOR: 0.48; 95% CI: 0.01-26.71) studies. Overall the study quality was good., Conclusion: The current evidence indicates that exposure to PPI is significantly associated with increased risk of IBD. Further, adequately powered studies from various parts of the world are needed for better quantification and generalizability of our findings., Prospero Protocol Registration Number: CRD42020209674.

Chronic rhinosinusitis has an incidence of 15% in India. Functional endoscopic sinus surgery (FESS), in case of failed medical management, is the current treatment protocol in Chronic rhinosinusitis. This study aims to assess the outcome of FESS as measured by subjective quality of life indices; Rhinosinusitis Disability Index (RSDI) and Sinonasal Outcome Test (SNOT-22. It also assesses the predictive factors which influence the outcome after FESS. The study was conducted among 100 patients with Chronic Rhinosinusitis who underwent FESS, after failure of medical management. Immunocompromised or pregnant patients and patients with history of previous sinus surgery or malignancy were excluded from the study. The evaluation was done using Lund Kennedy endoscopy scores, Lund Mackay CT scan scores and RSDI and SNOT-22 questionnaires (baseline and 3 months post-op). Statistical analysis was done using Wilcoxon signed-rank test, Kruskall Wallis test, Mann Whitney test and Chi-square test. p < 0.05 was considered significant. RSDI and SNOTT 22 scores showed a mean change 34.78 and 33.04 respectively after FESS, with a p value of < 0.001, which was highly significant. The pre-operative factors which predicted a poor quality of life after FESS were smoking, Allergy and Asthma. Higher pre-operative Endoscopic and CT scores resulted in an improved quality of life after FESS. Gender, concurrent septoplasty and sinonasal polyposis did not influence the quality of life outcomes after FESS. The study determines the quality of life after FESS and also analyses the factors responsible for poor prognosis after functional endoscopic sinus surgery. This study will enable the ENT surgeons to adequately counsel the patients before surgery., Competing Interests: Conflict of interestDr Suja S, Dr Jayakrishna A, Dr Devi P, Dr Vijendra S, Dr Panduranga M, Dr Sabah M declare that we have no conflict of interest., (© Association of Otolaryngologists of India 2020.)

Background and Objective: Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary disease with a high clinical and cost burden across the globe. Artificial intelligence (AI), an emerging area, has been used for various purposes in ARDS. We aim to summarize the currently available literature on various applications of AI in ARDS through a systematic review., Methodology: PubMed was searched from inception to February 2021 to collate all the studies. Additionally, a bibliographic search of included studies and a random search on Google, Google Scholar, and Research Gate were performed to identify relevant articles. Studies published in English language that employed data about developing and/or assessing the role of AI in the various aspects of ARDS were considered for this review. Three independent reviewers performed study selection and data extraction; any disagreements were settled through consensus or discussion with another member of the research team., Results: A total of 19 studies published between the year 2002 and 2020 were included. In these included studies, AI was used for various purposes in ARDS such as diagnosis (n = 10; 53 %), risk stratification (n = 1; 5 %), prediction of severity (n = 3; 17 %), management (n = 2; 10 %), prediction of mortality (n = 2; 10 %), and decision making (n = 1; 5 %). The area under the curve among the developed models in the included studies ranged between 0.8 and 1, which is considered to be very good to excellent., Conclusion: AI is revolutionizing healthcare and has a wide range of applications in ARDS, such as minimizing cost and enhancing outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The master epigenetic regulator lysine acetyltransferase (KAT) p300/CBP plays a pivotal role in neuroplasticity and cognitive functions. Recent evidence has shown that in several neurodegenerative diseases, including Alzheimer's disease (AD), the expression level and function of p300/CBP are severely compromised, leading to altered gene expression causing pathological conditions. Here, we show that p300/CBP activation by a small-molecule TTK21, conjugated to carbon nanosphere (CSP) ameliorates Aβ-impaired long-term potentiation (LTP) induced by high-frequency stimulation, theta burst stimulation, and synaptic tagging/capture (STC). This functional rescue was correlated with CSP-TTK21-induced changes in transcription and translation. Mechanistically, we observed that the expression of a large number of synaptic plasticity- and memory-related genes was rescued, presumably by the restoration of p300/CBP mediated acetylation. Collectively, these results suggest that small-molecule activators of p300/CBP could be a potential therapeutic molecule for neurodegenerative diseases like AD., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Toxicity induced by inorganic arsenic as AsO 3 3- ( iAs III ) is of global concern. Reliable detection of the maximum allowed contaminant level for arsenic in drinking water and in the cellular system remains a challenge for the water quality management and assessment of toxicity in the cellular milieu, respectively. A new Ir(III)-based phosphorescent molecule ( AS-1 ; λ Ext = 415 nm and λ Ems = 600 nm, Φ = 0.3) is synthesized for the selective detection of iAs III in an aqueous solution with a ratiometric luminescence response even in the presence of iAs V and all other common inorganic cations and anions. The relatively higher affinity of the thioimidazole ligand (HPBT) toward iAs III led to the formation of a fluorescent molecule iAs V -HPBT (λ Ext = 415 nm and λ Ems = 466 nm, Φ = 0.28) for the reaction of iAs III and AS-1 . An improved limit of quantitation (LOQ) down to 0.2 ppb is achieved when AS-1 is used in the CTAB micellar system. Presumably, the cationic surfactants favor the localization of AS-1 @CTAB Micelle in mitochondria of MCF7 cells, and this is confirmed from the images of the confocal laser fluorescence scanning microscopic studies. Importantly, cell viability assay studies confirm that AS-1 @CTAB Micelle induces dose-dependent detoxification of iAs III in live cells. Further, luminescence responses at 466 nm could be utilized for developing a hand-held device for the in-field application. Such a reagent that allows for ratiometric detection of iAs III with LOQ of 2.6 nM (0.5 ppb) in water, as well as helps in visualizing its distribution in mitochondria with a detoxifying effect, is rather unique in contemporary literature.

L-type Ca V 1.3 calcium channels are expressed on the dendrites and soma of neurons, and there is a paucity of information about its role in hippocampal plasticity. Here, by genetic targeting to ablate Ca V 1.3 RNA editing, we demonstrate that unedited Ca V 1.3 ΔECS mice exhibited improved learning and enhanced long-term memory, supporting a functional role of RNA editing in behavior. Significantly, the editing paradox that functional recoding of Ca V 1.3 RNA editing sites slows Ca 2+ -dependent inactivation to increase Ca 2+ influx but reduces channel open probability to decrease Ca 2+ influx was resolved. Mechanistically, using hippocampal slice recordings, we provide evidence that unedited Ca V 1.3 channels permitted larger Ca 2+ influx into the hippocampal pyramidal neurons to bolster neuronal excitability, synaptic transmission, late long-term potentiation, and increased dendritic arborization. Of note, RNA editing of the Ca V 1.3 IQ-domain was found to be evolutionarily conserved in mammals, which lends support to the importance of the functional recoding of the Ca V 1.3 channel in brain function.