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Parkinson's disease (PD) is an age-related chronic neurological condition characterized by progressive degeneration of dopaminergic neurons and the presence of Lewy bodies, primarily composed of alpha-synuclein and ubiquitin. The pathophysiology of PD encompasses alpha-synuclein aggregation, oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired autophagy and ubiquitin-proteasome systems. Among these, the Keap1-Nrf2 pathway is a key regulator of antioxidant defense mechanisms. Nrf2 has emerged as a crucial factor in managing oxidative stress and inflammation, and it also influences ubiquitination through p62 expression. Keap1 negatively regulates Nrf2 by targeting it for degradation via the ubiquitin-proteasome system. Disruption of the Nrf2-Keap1 pathway in PD affects cellular responses to oxidative stress and inflammation, thereby playing a critical role in disease progression. In addition, the role of neuroinflammation in PD has gained significant attention, highlighting the interplay between immune responses and neurodegeneration. This review discusses the various mechanisms responsible for neuronal degeneration in PD, with a special emphasis on the neuroprotective role of the Nrf2-Keap1 pathway. Furthermore, it explores the implications of inflammopharmacology in modulating these pathways to provide therapeutic insights for PD.

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Glomerulocystic kidney disease (GCKD) is a rare form of cystic renal disease. We report a four-week-old baby girl born to non-consanguineous parents; their antenatal third-trimester ultrasound showed severe oligohydramnios that required amnioinfusion. Post-natal ultrasound examination showed few tiny cysts (2-3mm) involving the cortices in bilateral kidneys. Kidney biopsy showed dilatation of Bowman's space and cystically dilated glomeruli, suggestive of GCKD. Whole exome sequencing revealed no pathogenic or likely pathogenic variant.

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Despite significant strides made in childhood survival during the last 75 years, India bears the largest burden of congenital heart disease (CHD) in the world. The care of a child with CHD requires multidisciplinary collaboration and development of distinct training opportunities in developing countries to ensure outcomes similar to those achieved in high-income countries. We present a commentary on the current state of pediatric cardiac critical care in India and propose pathways to fulfil the unmet needs of Indian children. The aim is to achieve self-reliance in pediatric cardiac services and to move towards optimal outcome and intact survival of children with CHD.

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We present a 49-year-old woman requiring living donor liver transplantation after liver metastasis from a pancreatic solid pseudopapillary tumor. After identifying a pancreatic mass and liver lesions, she underwent extensive surgical resection. Pathology revealed a solid pseudopapillary neoplasm of the head and body of the pancreas, extending into the peripancreatic soft tissues and confirmed to have spread to the liver. Subsequently, she underwent adjuvant chemotherapy and radiofrequency ablations of the new liver lesions. Despite immunotherapy and chemotherapy, there was a progression of the lesions. With interval growth of liver lesions, without evidence of extrahepatic disease, she underwent living donor liver transplantation.

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BACKGROUND: Changing lifestyles, health care, growing age, and life expectancy have contributed to the occurrence of old age in communities. The elderly population are rising who are aged 60 or older in the present scenario. They are more prone to psychosocial problems such as stress, loneliness, low self-esteem, and anxiety. These problems impact their psychological health. MATERIALS AND METHODS: This cross-sectional study was conducted at selected communities of Amritsar, Punjab. A total of 200 older adults were involved using the purposive sampling technique. Data were collected using a predesigned sociodemographic pro forma and a five-point Likert scale to assess psychosocial problems among the elderly. The data collection method employed was interviewed. In the psychosocial problems assessment tool, a total of 35 items were included, which were further categorized as follows: no psychosocial problem (0-35), mild psychosocial problem (36-70), moderate psychosocial problem (71-105), and severe psychosocial problem (106-140). RESULTS: The average age of the older adults was 69.31 ± 6.63 years, 65.5% were males and 34.5% were females. Regarding psychosocial problems, 69% had moderate, 16% had mild, 10.5% severe, and 4.5% had no problems. The median score was 90 (18). The median score was 17.50 (7) for stress, 38 (17.75) for loneliness, 18 (7.75) for anxiety, and 14 (7) for self-esteem. All the four domains, stress, loneliness, anxiety, and self-esteem, had a statistically significant relationship (P < 0.01). A statistically significant association was found between self-esteem, type of family, and anxiety with educational level. CONCLUSION: The study concluded that older adults in communities have significant psychosocial problems such as stress, loneliness, self-esteem, and anxiety. Collaboratively, health professionals, local community leaders, and social workers can formulate and execute a health awareness campaign to avoid these issues that cause the aged much anguish.

RésuméLes modes de vie changeants, les soins de santé, le vieillissement et l'espérance de vie accrue ont contribué à l'occurrence du vieillissement dans les communautés. La population âgée de 60 ans ou plus est en augmentation dans le contexte actuel. Ils sont plus sujets à des problèmes psychosociaux tels que le stress, la solitude, la faible estime de soi et l'anxiété. Ces problèmes ont un impact sur leur santé psychologique.Matériel et Méthodes:Cette étude transversale a été menée dans des communautés sélectionnées d'Amritsar, au Pendjab. Au total, 200 personnes âgées ont été incluses en utilisant la technique d'échantillonnage raisonné. Les données ont été collectées à l'aide d'un formulaire sociodémographique préconçu et d'une échelle de Likert à cinq points pour évaluer les problèmes psychosociaux chez les personnes âgées. La méthode de collecte de données utilisée était l'entrevue. Dans l'outil d'évaluation des problèmes psychosociaux, un total de 35 items ont été inclus, qui ont été ensuite catégorisés comme suit: aucun problème psychosocial (0­35), problème psychosocial léger (36­70), problème psychosocial modéré (71­105) et problème psychosocial sévère (106­140).Résultats:L'âge moyen des personnes âgées était de 69,31 ± 6,63 ans, 65,5 % étaient des hommes et 34,5 % étaient des femmes. En ce qui concerne les problèmes psychosociaux, 69 % avaient un problème modéré, 16 % un problème léger, 10,5 % un problème sévère et 4,5 % n'avaient aucun problème. Le score médian était de 90 (18). Le score médian était de 17,50 (7) pour le stress, 38 (17,75) pour la solitude, 18 (7,75) pour l'anxiété et 14 (7) pour l'estime de soi. Les quatre domaines, le stress, la solitude, l'anxiété et l'estime de soi, avaient une relation statistiquement significative (P < 0,01). Une association statistiquement significative a été trouvée entre l'estime de soi, le type de famille et l'anxiété avec le niveau d'éducation.Conclusion:L'étude a conclu que les personnes âgées dans les communautés ont des problèmes psychosociaux significatifs tels que le stress, la solitude, l'estime de soi et l'anxiété. En collaboration, les professionnels de la santé, les leaders communautaires locaux et les travailleurs sociaux peuvent formuler et exécuter une campagne de sensibilisation à la santé pour éviter ces problèmes qui causent beaucoup de souffrance aux personnes âgées.

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The abnormal accumulation of fibrillar α-synuclein in the substantia nigra contributes to Parkinson's disease (PD). Chemical chaperones like 4-phenyl butyric acid (4PBA) show neuroprotective potential, but high doses are required. A derivative, 5-phenyl valeric acid (5PVA), has reported therapeutic potential for PD by reducing Pael-R expression. This study assessed 5PVA's efficacy in PD animals and its molecular mechanism. In vitro studies revealed 5PVA's anti-aggregation ability against alpha-synuclein and neuroprotective effects on SHSY5Y neuroblastoma cells exposed to rotenone. PD-like symptoms were induced in SD rats with rotenone, followed by 5PVA treatment at 100 mg/kg and 130 mg/kg. Behavioral analysis showed significant improvement in memory and motor activity with 5PVA administration. Histopathological studies demonstrated normal neuronal histoarchitecture in mid-brain tissue sections of 5PVA-treated animals compared to the PD group. mRNA studies revealed significant suppression in the expression of various protein folding and heat-shock protein markers in the 5PVA-treated group. In conclusion, 5PVA, with its anti-aggregation ability against alpha-synuclein, acts as a chemical chaperone, showing potential as a therapeutic candidate for PD treatment.

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Linalool is a neuroprotective monoterpene found in essential oils from aromatic plants. Linalool's effectiveness in AD animal models has been established previously, but its mechanisms of action remain unclear. Therefore, this study aims to investigate whether linalool binds directly to the amyloid beta (Aß) fibrils to understand it's role in preventing neurodegeneration. The anti-aggregation ability of Linalool was determined using Dithiothreitol (DTT), and thermal aggregation assays followed by Thioflavin T (ThT) binding assay. AD animals were treated with Linalool, and Thioflavin T staining was used to check the binding of linalool to Aß fibrils in rat brain tissue sections. Preliminary studies revealed the anti-aggregation potential of linalool under the thermal and chemical stimulus. Further, in ThT binding assay Linalool inhibited Aß aggregation, binding directly to Aß fibrils. The reduced fluorescence intensity of ThT in AD brain tissues following linalool administration, highlights its neuroprotective potential as a therapeutic agent for AD.

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The present study evaluates the adsorption efficiency of low-cost carbonaceous adsorbents as fly ash (FA), saw dust biochar (SDB) (untreated and alkali - treated), live/dead pulverized white rot fungus Hypocrea lixii biomass encapsulated in sodium alginate (SA) against the commercially available activated carbon (AC) and graphene oxide (GO) SA beads for removal of benzene phenol derivatives - Bisphenol A (BPA)/triclosan (TCS). Amongst bi - and tri - composites SA beads, tri-composite beads comprising of untreated flyash - dead fungal biomass - sodium alginate (UFA - DB - SA) showed at par results with commercial composite beads. The tri - composite beads with point zero charge (Ppzc) of 6.2 was characterized using FTIR, XRD, surface area BET and SEM-EDX. The batch adsorption using tri - composite beads revealed removal of 93% BPA with adsorption capacity of 16.6 mg/g (pH 6) and 83.72% TCS with adsorption capacity of 14.23 mg/g (pH 5), respectively at 50 ppm initial concentration with 6 % adsorbent dose in 5 h. Freundlich isotherm favoring multilayered adsorption provided a better fit with r2 of 0.9674 for BPA and 0.9605 for TCS respectively. Intraparticle diffusion model showed adsorption of BPA/TCS molecules to follow pseudo - second order kinetics with boundary layer diffusion governed by first step of fast adsorption and intraparticle diffusion within pores by second slow adsorption step. Thermodynamic parameters (ΔH°, ΔS°, ΔG°) revealed adsorption process as exothermic, orderly and spontaneous. Methanol showed better desorbing efficiency leading to five cycles reusability. The phytotoxicity assay revealed increased germination rate of mung bean (Vigna radiata) seeds, sprinkled with post adsorbed treated water (0 h, 5 h and 7 h) initially spiked with 50 ppm BPA/TCS. Overall, UFA - DB - SA tri - composite beads provides a cost effective and eco - friendly matrix for effective removal of hydrophobic recalcitrant compounds.

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Abernethy malformation or congenital extrahepatic portosystemic shunt is an extremely rare condition whereby the portomesenteric blood drains into a systemic vein and bypasses the liver through a complete or partial shunt. Severe complications include hyperammonemia and encephalopathy, benign and malignant liver tumors, and hepatopulmonary syndrome. We describe a case where a female adult diagnosed with congenital extrahepatic portosystemic shunt subsequently developed focal nodular hyperplasia and then hepatocellular carcinoma.

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Introduction: Depression can affect oral health as a result of neglecting oral hygiene procedures which leads to an increased risk of dental caries and periodontal disease. Aim: To determine relationship between oral health and depression among elder people residing in old age homes of Mathura city. Materials and Methods: The study was conducted among 500 subjects aged ≥60 years where dental condition, number of missing teeth, removable denture wearing, teeth mobility, periodontal condition, pocket depth, loss of attachment, and depression according to the Patient Health Questionnaire-9 scale were assessed. Results: Regression analysis showed a positive relationship of the PHQ-9 value with DMFT and MT. Conclusion: Among people aged 60 years and over, severity of depression increased with higher number of MT and DT.

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A commonly encountered challenge with freeze-dried drug products is glass vial fogging. Fogging is characterized by a thin layer of product deposited upon the inner surface of the vial above the lyophilized cake. While considered to be a routine cosmetic defect in many instances, fogging around the shoulder and neck of the vial may potentially impact container closure integrity and reject rates during inspection. In this work, the influence of processing conditions i.e. vial pre-treatment, lyophilization cycle modifications and filling conditions on fogging was evaluated. A battery of analytical techniques was employed to investigate factors affecting glass vial fogging. A fogging score was used to quantify its severity in freeze-dried products. Additionally, a dye-based method was used to study solution upcreep (Marangoni flow) following product filling. Our lab-scale results indicate measurable improvement in fogging following the addition of an annealing step in the lyophilization cycle. Pre-freeze isothermal holding of the vials (at 5°C on the lyophilizer shelf) for an extended duration indicated a reduction in fogging whereas an increase in the freezing time exhibited no effect on fogging. Vial pre-treatment conditions were critical determinants of fogging for Type 1 vials whereas they had no impact on fogging in TopLyo® vials. The headspace relative humidity (RH) investigation also indicated sufficient increase in the water vapor pressure inside the vial to be conducive to the formulation of a hydration film - the precursor to Marangoni flow.

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Aim: To examine the characteristics of acid attack survivors who were aged ≤16 years at the time of the assault. Methods: Case files from the Chhanv and the Laxmi Foundations in India were accessioned for cases of acid attacks involving children and adolescents (≤16 years). Details of the age, sex, reason for the attack, injuries sustained and possible outcomes were recorded. Results: Ten cases were identified that involved eight girls (aged 3-16 years) and two boys (12 and 14 years). The head and neck were the primary targets in all cases. The primary reasons for the attacks involving adolescent girls were punishment for refusing sexual advances from older males and family violence/child abuse. The two male victims were assaulted as part of property dispute and gang violence. Penalties varied greatly with prison sentences (when handed down) ranging from <1 year to 10 years. Conclusion: The number of cases of paediatric acid attacks appear small, with motivations for the attacks including responses to spurned sexual advances, domestic violence/child abuse, criminal gang activities and ostensibly at random. Nongovernment organisations are vital in the rehabilitation of victims. It is of concern that dissemination on social networks and publicity through the media may lead to an increase in number of cases.

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BACKGROUND: As part of the Patient Protection and Affordable Care Act, some states expanded Medicaid eligibility to adults with incomes below 138% of the federal poverty line. While this resulted in an increased proportion of insured residents, its impact on the diagnosis and treatment of hepatopancreaticobiliary (HPB) cancers has not been studied. STUDY DESIGN: The National Cancer Database (NCDB) from 2010 to 2017 was used. Patients diagnosed with HPB malignancies in states which expanded in 2014 were compared to patients in non-expansion states. Subset analyses of patients who underwent surgery and those in high-risk socioeconomic groups were performed. Outcomes studied included initiation of treatment within 30 days of diagnosis, stage at diagnosis, care at high volume or academic center, perioperative outcomes, and overall survival. Adjusted difference-in-differences analysis was performed. RESULTS: A total of 345,684 patients were included, of whom 55% resided in non-expansion states and 54% were diagnosed with pancreatic cancer. Overall survival was higher in states with Medicaid expansion (HR .90, 95% CI [.88-.92], P < .01). There were also better postoperative outcomes including 30-day mortality (.67 [.57-.80], P < .01) and 30-day readmissions (.87 [.78-.97], P = .02) as well as increased likelihood of having surgery in a high-volume center (1.42 [1.32-1.53], P < .01). However, there were lower odds of initiating care within 30 days of diagnosis (.77 [.75-.80], P < .01) and higher likelihood of diagnosis with stage IV disease (1.09 [1.06-1.12], P < .01) in expansion states. CONCLUSION: While operative outcomes and overall survival from HPB cancers were better in states with Medicaid expansion, there was no improvement in timeliness of initiating care or stage at diagnosis.

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The Endoplasmic reticulum (ER), a critical cellular organelle, maintains cellular homeostasis by regulating calcium levels and orchestrating essential functions such as protein synthesis, folding, and lipid production. A pivotal aspect of ER function is its role in protein quality control. When misfolded proteins accumulate within the ER due to factors like protein folding chaperone dysfunction, toxicity, oxidative stress, or inflammation, it triggers the Unfolded protein response (UPR). The UPR involves the activation of chaperones like calnexin, calreticulin, glucose-regulating protein 78 (GRP78), and Glucose-regulating protein 94 (GRP94), along with oxidoreductases like protein disulphide isomerases (PDIs). Cells employ the Endoplasmic reticulum-associated degradation (ERAD) mechanism to counteract protein misfolding. ERAD disruption causes the detachment of GRP78 from transmembrane proteins, initiating a cascade involving Inositol-requiring kinase/endoribonuclease 1 (IRE1), Activating transcription factor 6 (ATF6), and Protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathways. The accumulation and deposition of misfolded proteins within the cell are hallmarks of numerous neurodegenerative diseases. These aberrant proteins disrupt normal neuronal signalling and contribute to impaired cellular homeostasis, including oxidative stress and compromised protein degradation pathways. In essence, ER stress is defined as the cellular response to the accumulation of misfolded proteins in the endoplasmic reticulum, encompassing a series of signalling pathways and molecular events that aim to restore cellular homeostasis. This comprehensive review explores ER stress and its profound implications for the pathogenesis and progression of neurodegenerative diseases.

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Accurate hydrogen leakage detection is a major requirement for the safe and widespread integration of this fuel in modern energy production devices, such as fuel cells. Quasi-1D nanowires of seven different metal oxides (CuO, WO3, Nb-added WO3, SnO2, ZnO, α-Bi2O3, NiO) were integrated into a conductometric sensor array to evaluate the hydrogen-sensing performances in the presence of interfering gaseous compounds, namely carbon monoxide, nitrogen dioxide, methane, acetone, and ethanol, at different operating temperatures (200-400 °C). Principal component analysis (PCA) was applied to data extracted from the array, demonstrating the ability to discriminate hydrogen over other interferent compounds. Moreover, a reduced array formed by only five sensors is proposed. This compact array may be easily implementable into artificial olfaction systems used in real hydrogen detection applications.

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STATEMENT OF PROBLEM: Platform switching using narrower abutments than the implant platform has been used to reduce marginal bone loss (MBL) surrounding dental implants. While platform switching has been reported to prevent initial peri-implant bone loss, available data regarding the use of the platform-switching implant abutment configuration with long-term follow-up has been sparse; thus, the systematic review was planned to evaluate the best available evidence for the use of the platform switching technique. PURPOSE: The purpose of this systematic review was to answer the specific question, "Is there a difference between platform-matching implant abutment configurations and platform-switching implant abutment configurations in terms of MBL changes around endosseous implants"? MATERIAL AND METHODS: The PubMed/Medline, Scopus, Google Scholar, and Lilac databases were searched by 2 independent reviewers for articles published between January 2000 and July 2022. Platform-switched versus platform-matched implants were examined for changes in MBL in human randomized clinical trials (RCTs) and potential clinically controlled cohort studies (PCCS). RESULTS: Overall, 4 eligible studies were included and critically evaluated to summarize their findings. The follow-up period of the included studies was between 5 and 10 years. Two of the included studies showed a mean ±standard deviation of 0.6 ±0.20 mm MBL at 5 years and 1.20 ±0.21 mm at 10 years for the platform switched (PS) technique and 1.1 ±0.3 mm and 1.24 ±0.39 mm MBL for the platform matched (PM) technique. Another study showed marginal bone level changes for the platform-switched technique to be 0.18 ±0.14 mm as compared with the platform matched technique (0.80 ±0.40 mm). In one of the studies published in 2019, the mean estimated difference in the marginal bone levels of PS- and PM-restored implants after 5 years was reported to be 0.29 mm. The descriptive analysis of 4 RCTs indicated that platform-switched implant-to-abutment connections reduced average marginal bone loss surrounding implants compared with platform-matched implant-to-abutment connections, favoring the platform-switched approach. CONCLUSIONS: Platform switching appears to be a beneficial approach for retaining the crestal bone around dental implants.

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The present research was designed to determine the nutritive value of the liver and intestine of fish, Sperata seenghala, the impact of effluence load on limnological parameters of water and proximate composition of fish organs, especially on fatty acids, liver enzymatic activities, seasonal variations in the nutritional profile of fish, and to check and compare the pollution status of Ramsar sites in Punjab by calculating the water quality index, heavy metal pollution index, and metal index from June 2018 to August 2020. WQI of Harike wetland was found to be 53.95, which depicts that water quality in this region is "poor". At Nangal wetland, water quality index was reported to be "excellent" quality water and fit for the whole ecological unit. Overall heavy metal pollution index for Harike wetland was reported 174.569, whereas for Nangal wetland it was 5.994, depicting massive contaminant loads in a polluted region. MI value was also recorded as being higher (6.9336) in polluted habitat than in control habitat (0.8175). In fish liver, significant (p < 0.05) higher mean total lipids (6.73%), total proteins (3.98%), moisture (77.69%), ash (3.56%), and carbohydrates (3.79%) were observed in the samples from Nangal wetland than Harike wetland. A similar trend was reported in all biochemical contents of the fish intestine. Enzyme activities such as aspartate-aminotransferase and alanine-aminotransferase were significantly elevated (p < 0.05) in the specimens collected from the polluted region. The mean total n-3 (except in spring), n-6 polyunsaturated fatty acids (except in winter), and average monounsaturated and saturated fatty acids diminished significantly (p < 0.05) in the liver of fish from contaminated habitat than control site. In the intestine of fish collected from the polluted region, significant reductions in the mean total n-3 (except in autumn as well as summer), total n-6 PUFAs (in autumn and winter), and total SFAs were reported than control site.

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Aggregated α-synuclein (α-syn) present inside small cytoplasmic inclusions in the substantia nigra region marks the major pathological hallmark of Parkinson's disease (PD) and makes it an attractive target for the drug development process. Certain small-molecule chaperones (such as DCA, UDCA, TUDCA) presented the ability to prevent misfolding and aggregation of α-syn as well as to disentangle mature α-syn amyloid fibrils. However, due to toxicity constraints, these small molecules could not be translated into clinical settings. Computational biology methods and bioinformatics approaches allow virtual screening of a large number of molecules, with reduced side effects and better efficacy. In the present study, a library of 10,928 derivatives was generated using DCA, UDCA, and TUDCA bile acid scaffolds and analysed for their binding affinity, pharmacokinetic properties, and drug likeliness profile, to come up with promising compounds with reduced toxicity and better chaperone ability. Molecular docking revealed that with respect to their free binding energy, C1-C25 have the lowest binding energy and bind significantly to recombinantly assembled E46K α-syn fibrils (PDB ID-6UFR). In silico ADME predictions revealed that all these compounds had minimal toxic effects and had good absorption as well as solubility characteristics. Simulation studies further showed that the imidazole ring-based TUDCA derivatives interacted better with the protein in comparison to the others. The proposed study has identified potent chemical chaperones (C2 and C3) as effective therapeutic agents for Parkinson's disease, and further in vitro and in vivo testing will be undertaken to substantiate their potential as novel drugs.