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Management of chronic obesity-associated metabolic disorders is a key challenge for biomedical researchers. During chronic obesity, visceral adipose tissue (VAT) undergoes substantial transformation characterized by a unique lipid-rich hypoxic AT microenvironment which plays a crucial role in VAT dysfunction, leading to insulin resistance (IR) and type 2 diabetes. Here, we demonstrate that obese AT microenvironment triggers the release of miR-210-3p microRNA-loaded extracellular vesicles from adipose tissue macrophages, which disseminate miR-210-3p to neighboring adipocytes, skeletal muscle cells, and hepatocytes through paracrine and endocrine actions, thereby influencing insulin sensitivity. Moreover, EVs collected from Dicer-silenced miR-210-3p-overexpressed bone marrow-derived macrophages induce glucose intolerance and IR in lean mice. Mechanistically, miR-210-3p interacts with the 3'-UTR of GLUT4 mRNA and silences its expression, compromising cellular glucose uptake and insulin sensitivity. Therapeutic inhibition of miR-210-3p in VAT notably rescues high-fat diet-fed mice from obesity-induced systemic glucose intolerance. Thus, targeting adipose tissue macrophage-specific miR-210-3p during obesity could be a promising strategy for managing IR and type 2 diabetes.
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Transportador de Glucose Tipo 4 , Resistência à Insulina , Macrófagos , MicroRNAs , Obesidade , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Obesidade/metabolismo , Obesidade/genética , Obesidade/patologia , Macrófagos/metabolismo , Camundongos , Transportador de Glucose Tipo 4/metabolismo , Transportador de Glucose Tipo 4/genética , Masculino , Camundongos Endogâmicos C57BL , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Humanos , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/metabolismo , Intolerância à Glucose/genética , Intolerância à Glucose/patologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologiaRESUMO
Biobank projects are generating genomic data for many thousands of individuals. Computational methods are needed to handle these massive data sets, including genetic ancestry (GA) inference tools. Current methods for GA inference do not scale to biobank-size genomic datasets. We present Rye-a new algorithm for GA inference at biobank scale. We compared the accuracy and runtime performance of Rye to the widely used RFMix, ADMIXTURE and iAdmix programs and applied it to a dataset of 488221 genome-wide variant samples from the UK Biobank. Rye infers GA based on principal component analysis of genomic variant samples from ancestral reference populations and query individuals. The algorithm's accuracy is powered by Metropolis-Hastings optimization and its speed is provided by non-negative least squares regression. Rye produces highly accurate GA estimates for three-way admixed populations-African, European and Native American-compared to RFMix and ADMIXTURE (${R}^2 = \ 0.998 - 1.00$), and shows 50× runtime improvement compared to ADMIXTURE on the UK Biobank dataset. Rye analysis of UK Biobank samples demonstrates how it can be used to infer GA at both continental and subcontinental levels. We discuss user consideration and options for the use of Rye; the program and its documentation are distributed on the GitHub repository: https://github.com/healthdisparities/rye.
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Genética Populacional , Secale , Humanos , Secale/genética , Bancos de Espécimes Biológicos , Algoritmos , Genômica , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Nonalcoholic fatty liver disease (NAFLD) is associated with an increased ratio of classically activated M1 macrophages/Kupffer cells to alternatively activated M2 macrophages, which plays an imperative role in the development and progression of NAFLD. However, little is known about the precise mechanism behind macrophage polarization shift. Here, we provide evidence regarding the relationship between the polarization shift in Kupffer cells and autophagy resulting from lipid exposure. High-fat and high-fructose diet supplementation for 10 weeks significantly increased the abundance of Kupffer cells with an M1-predominant phenotype in mice. Interestingly, at the molecular level, we also observed a concomitant increase in expression of DNA methyltransferases DNMT1 and reduced autophagy in the NAFLD mice. We also observed hypermethylation at the promotor regions of autophagy genes (LC3B, ATG-5, and ATG-7). Furthermore, the pharmacological inhibition of DNMT1 by using DNA hypomethylating agents (azacitidine and zebularine) restored Kupffer cell autophagy, M1/M2 polarization, and therefore prevented the progression of NAFLD. We report the presence of a link between epigenetic regulation of autophagy gene and macrophage polarization switch. We provide the evidence that epigenetic modulators restore the lipid-induced imbalance in macrophage polarization, therefore preventing the development and progression of NAFLD.
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Autofagia , Polaridade Celular , Macrófagos , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Autofagia/efeitos dos fármacos , Autofagia/genética , Dieta Hiperlipídica/efeitos adversos , Dieta Ocidental/efeitos adversos , Epigênese Genética/efeitos dos fármacos , Fígado/citologia , Fígado/fisiopatologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Azacitidina/farmacologia , Azacitidina/uso terapêutico , Inibidores Enzimáticos/farmacologia , Metilação de DNA/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Células RAW 264.7 , Técnicas de Silenciamento de GenesRESUMO
Acute-on-chronic liver failure (ACLF) is a global health problem. Little scientific evidence exists on its prevalence in autoimmune hepatitis. Treatment response and mortality outcomes have also been reported differently. The study was conducted to estimate the overall prevalence of ACLF among patients with autoimmune hepatitis (AIH) and determine the associated treatment response and mortality. We scrutinized wide literature in Scopus, PubMed, Embase, Web of Science, and Cochrane, and assessed published articles completely, studies performed and reported from around the globe, until December 07, 2023, according to the PROSPERO registered protocol (CRD42023412176). Studies (retrospective and prospective cohort study type) that stated the ACLF development among established AIH cases were considered. Features of the study, duration of follow-up, and numeric patient information were retrieved from the studies included. The research paper quality was checked for risk of bias. Random effect meta-analysis with metaregression and subsection scrutinies were performed with R. The main outcome was the collective prevalence of ACLF in the AIH patients, whereas treatment response and mortality in AIH-associated ACLF were secondary outcomes. Six studies were involved with confirmed diagnoses in 985 AIH patients for the data synthesis. The pooled prevalence of ACLF in the explored patients was 12% (95% CI: 8-17) ( P =0.01). Heterogeneity was found to be high in the present meta-analysis ( I2 =72%; P < 0.01). For the secondary endpoint analysis, the pooled prevalence of complete remission at 1-year follow-up was 71% (0.52; 0.85), and mortality from the ACLF-AIH patient population was 32% (95% CI: 18-50). Sensitivity analysis showed no influence on the overall estimations of the pooled prevalence of ACLF by omitting studies one by one. One in 10 AIH patients likely present with ACLF. The response to treatment is seen in two-thirds of patients, and mortality is high.
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Insuficiência Hepática Crônica Agudizada , Hepatite Autoimune , Humanos , Hepatite Autoimune/complicações , Hepatite Autoimune/epidemiologia , Hepatite Autoimune/mortalidade , Insuficiência Hepática Crônica Agudizada/epidemiologia , Insuficiência Hepática Crônica Agudizada/mortalidade , Prevalência , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) is the third most common cancer-related cause of death worldwide. Although Sorafenib is the standard systemic therapy for treating HCC, but it develops resistance very quickly, leading to poor prognosis. The current study was planned to explore the effect of l-methionine on the anticancer activity of Sorafenib in HCC. Ten millimolar of l-methionine treatment significantly reduced the IC50 of Sorafenib from 5.513 ± 0.171 to 0.8095 ± 0.0465 µM in HepG2 cell line. It also resulted in concomitant increase in oxidative stress and deactivation of ERK/AMPK/AKT pathway. Additionally, it also resulted in the increased expression of dual specificity phosphatase 3 (DUSP3). In a rat model of sorafenib-resistant HCC induced by diethylnitrosamine (DEN) (100 mg/L/day) and Sorafenib (10 mg/kg), l-methionine (300 and 500 mg/kg/day) supplementation overcame the drug resistance, as indicated by the reduced formation of surface tumor nodules, prevention of cellular hypertrophy, hyperplasia and inflammation, and improved animal survival. Furthermore, l-methionine in combination with Sorafenib also inhibited AMPK/AKT and ERK pathway. At chromatin level, l-methionine supplementation prevented global methylation of H3K27me3, an inactivation mark, and demethylation of H3K36me2, an activation mark. Interestingly, our findings suggest that inhibition of the ERK pathway via increased activity of DUSP3 is epigenetically regulated. Besides, chromatin immunoprecipitation data exhibited augmented H3K36me2 (an activation mark) levels on the DUSP3 promoter region. To the best of our knowledge, we are the first to report that l-methionine supplementation improves the chemosensitivity in Sorafenib-resistant HCC via modulating the epigenetic landscape and can be a potential therapeutic strategy.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Ratos , Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Fosfatase 3 de Especificidade Dupla/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , HumanosRESUMO
BACKGROUND: Aberrant gluconeogenesis is considered among primary drivers of hyperglycemia under insulin resistant conditions, with multiple studies pointing towards epigenetic dysregulation. Here we examine the role of miR-721 and effect of epigenetic modulator laccaic acid on the regulation of gluconeogenesis under high fat diet induced insulin resistance. RESULTS: Reanalysis of miRNA profiling data of high-fat diet-induced insulin-resistant mice model, GEO dataset (GSE94799) revealed a significant upregulation of miR-721, which was further validated in invivo insulin resistance in mice and invitro insulin resistance in Hepa 1-6 cells. Interestingly, miR-721 mimic increased glucose production in Hepa 1-6 cells via activation of FOXO1 regulated gluconeogenic program. Concomitantly, inhibition of miR-721 reduced glucose production in palmitate induced insulin resistant Hepa 1-6 cells by blunting the FOXO1 induced gluconeogenesis. Intriguingly, at epigenetic level, enrichment of the transcriptional activation mark H3K36me2 got decreased around the FOXO1 promoter. Additionally, identifying targets of miR-721 using miRDB.org showed H3K36me2 demethylase KDM2A as a potential target. Notably, miR-721 inhibitor enhanced KDM2A expression which correlated with H3K36me2 enrichment around FOXO1 promoter and the downstream activation of the gluconeogenic pathway. Furthermore, inhibition of miR-721 in high-fat diet-induced insulin-resistant mice resulted in restoration of KDM2A levels, concomitantly reducing FOXO1, PCK1, and G6PC expression, attenuating gluconeogenesis, hyperglycemia, and improving glucose tolerance. Interestingly, the epigenetic modulator laccaic acid also reduced the hepatic miR-721 expression and improved KDM2A expression, supporting our earlier report that laccaic acid attenuates insulin resistance by reducing gluconeogenesis. CONCLUSION: Our study unveils the role of miR-721 in regulating gluconeogenesis through KDM2A and FOXO1 under insulin resistance, pointing towards significant clinical and therapeutic implications for metabolic disorders. Moreover, the promising impact of laccaic acid highlights its potential as a valuable intervention in managing insulin resistance-associated metabolic diseases.
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Gluconeogênese , Resistência à Insulina , Histona Desmetilases com o Domínio Jumonji , MicroRNAs , Animais , Masculino , Camundongos , Dieta Hiperlipídica , Epigênese Genética , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Gluconeogênese/genética , Gluconeogênese/fisiologia , Resistência à Insulina/fisiologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/genéticaRESUMO
Background: Health-related quality of life is rapidly becoming recognized as an important indicator of how a disease affects patient lives and for evaluating the quality of care, especially for chronic conditions such as chronic kidney disease (CKD). Objectives: This study is an attempt to assess the quality of life in patients with chronic kidney disease at MMIMSR and also identify characteristics that may be associated with their worsening quality of life. Materials and Methods: This cross-sectional investigation was conducted at the in-patient department (IPD) of the MMIMSR hospital. This study included 105 CKD patients and used a systematic random sampling method for quantitative analysis. This study utilized a 36-item short-form SF-36 (v1.3) questionnaire to assess HRQoL in CKD patients. Descriptive statistics were employed at the baseline. Chi square and ANOVA were used to draw comparisons between two groups or more than two groups, respectively. Logistic regression analysis was utilized to identify the potential QoL determinants. A p value of 0.05 or lower was used to determine statistical significance. Results: Among a total of 105 participants, the mean (±standard deviation) age was found to be 54.53 ± 13.47 years; 48 were male patients, and 57 were female patients. Diabetes Mellitus (61.9%), hypertension (56.2%), chronic glomerulonephritis (7.6%), chronic pyelonephritis (6.7%), and polycystic kidney disease (5.7%) were identified to be the most frequent disorders associated with CKD. The current study also demonstrated that the HRQoL score domains such as symptom problem list, the effect of kidney disease, and the burden of kidney disease decline significantly and progressively as the patient advances into higher stages of CKD (p = 0.005). A similar pattern was observed in work status, sleep, and general health (p < 0.005). Additionally, a statistically significant difference was noted for cognitive function, quality of social interaction, overall health, dialysis staff encouragement, patient satisfaction, social support, physical functioning, role of physical health, pain, emotional well-being, role of emotional health, social functioning, and energy fatigue (p < 0.005). The mean difference for PCS and MCS based on CKD stages was found to be statistically significant (p < 0.005). The PCS and MCS showed a positive correlation with GFR (r = 0.521), and Hb (r = 0.378), GFR (r = 0.836), and Hb (r = 0.488), respectively. Conclusions: The findings of this study demonstrated that a significant decrease in HRQoL was observed among CKD patients, with a progressive deterioration of HRQoL dimensions as the patient advances to end-stage renal disease. This study also revealed that CKD imposes various restrictions on patients' day-to-day lives, particularly in terms of their physical and mental functioning, even in the initial stages of the disease.
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Qualidade de Vida , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Qualidade de Vida/psicologia , Estudos Transversais , Diálise Renal , Insuficiência Renal Crônica/psicologia , HospitaisRESUMO
PURPOSE: To study and analyse the radiological and surgical findings of 24 cochlear implantees with SMS type II cochleovestibular malformation and to compare their outcomes in terms of hearing and speech gains pre- and postoperatively. METHODS: Retrospective analysis of cochlear implanted candidates over a period of 8 year 6 months from 3 institutions was undertaken and 24 patients suffering from prelingual profound congenital sensori-neural hearing loss along with the presence of SMS type II cochleovestibular malformation were studied. Preoperative radiology, surgical difficulties and complication, and postoperative hearing and speech outcomes up to a period of 2 years, using IT-MAIS and SIR scores were noted. Statistical comparison pre- and postimplantation was done using Wilcoxon signed rank test and a p value of < 0.05 was considered statistically significant. RESULTS: In 24 cases, we encountered four cases of SMS type IIa malformation with a smaller modiolus, while the rest 20 were type SMS type IIb with partially defective modiolus. Intraoperatively, CSF leak was observed in 11 patients. Complete electrode insertion and good electrical response (NRT) was detected in all. No facial nerve anomaly was encountered. IT-MAIS and SIR scores increased from a preoperative mean of 5.6 and 1.16-34.56 and 3.88 after 2 years postsurgery, respectively and this difference was found to be statistically significant. CONCLUSION: Our experience with SMS Type II malformations show promising and motivating results with less chances of complications. Proper evaluation and surgical planning preoperatively can lead to an uneventful surgery with good outcomes. A simple and uniform classification system of these anomalies is a must for appropriate prognostication and right decision making.
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Implante Coclear , Implantes Cocleares , Perda Auditiva Neurossensorial , Percepção da Fala , Cóclea/cirurgia , Implante Coclear/métodos , Implantes Cocleares/efeitos adversos , Perda Auditiva Neurossensorial/cirurgia , Humanos , Estudos Retrospectivos , Percepção da Fala/fisiologia , Resultado do TratamentoRESUMO
Chronic wounds such as diabetic ulcers are a major complication in diabetes caused by hyperglycemia, prolonged inflammation, high oxidative stress, and bacterial bioburden. Bioactive biopolymers have been found to have a biological response in wound tissue microenvironments and are used for developing advanced tissue engineering strategies to enhance wound healing. These biopolymers possess innate bioactivity and are biodegradable, with favourable mechanical properties. However, their bioactivity is highly dependent on their structural properties, which need to be carefully considered while developing wound healing strategies. Biopolymers such as alginate, chitosan, hyaluronic acid, and collagen have previously been used in wound healing solutions but the modulation of structural/physico-chemical properties for differential bioactivity have not been the prime focus. Factors such as molecular weight, degree of polymerization, amino acid sequences, and hierarchical structures can have a spectrum of immunomodulatory, anti-bacterial, and anti-oxidant properties that could determine the fate of the wound. The current narrative review addresses the structure-function relationship in bioactive biopolymers for promoting healing in chronic wounds with emphasis on diabetic ulcers. This review highlights the need for characterization of the biopolymers under research while designing biomaterials to maximize the inherent bioactive potency for better tissue regeneration outcomes, especially in the context of diabetic ulcers.
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A comprehensive exploration of the intriguing phenomena known as the spin Nernst effect (SNE) and the spin Hall effect (SHE) within the context of nonmagnetic strong topological insulatorZnCu2SnSe4, has been carried out employing first-principles calculations. Our theoretical calculations unveil significantly large intrinsic spin Nernst conductivity (SNC) and spin Hall conductivity (SHC) in the bulk topological insulatorZnCu2SnSe4. Delving deeper into the intricacies of our findings, we elucidate how the inverted band order in the topological materials drastically influences the spin Berry curvature, consequently exerting a profound impact on SHC and SNC. Detailed analyses reveal that the contribution from the bulk to the generation of pure spin current in a topological insulator is comparable to that of a surface. This underscores the potential role of topological insulators in the development of spin-switching devices. We present compelling evidence thatZnCu2SnSe4holds immense promise as an optimal candidate for the generation of pure spin currents, achieved through the application of both thermal gradients and electric fields. This, in turn, opens up exciting avenues for its utilization in the realms of spin-caloritronics, spin-orbitronics, and spintronics.
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Malignancies in paediatric age group are the second leading cause of death, next only to accidents. The variety of malignancies involving the head and neck region in paediatric age group is bewildering. Rhabdomyosarcoma of thyroid gland is one such entity very rarely seen. We present the case of an adolescent who presented with a neck mass and suffered rapid deterioration. Establishment of final diagnosis was possible only because of a skilfully performed pathological examination which revealed a thyroid gland rhabdomyosarcoma. An alveolar variety of rhabdomyosarcoma presenting in the thyroid gland is extremely rare. To the best of our knowledge, only two cases of the aforementioned are documented as yet. Through this report, we aim at highlighting the possibility of such an occurrence and vigilance on part of the treating surgeon so that timely intervention can be instituted.
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In recent years, a number of bulk materials and heterostructures have been explored due their connections with exotic materials phenomena emanating from flat band physics and strong electronic correlation. The possibility of realizing such fascinating material properties in simple realistic nanostructures is particularly exciting, especially as the investigation of exotic states of electronic matter in wire-like geometries is relatively unexplored in the literature. Motivated by these considerations, we introduce in this work carbon Kagome nanotubes (CKNTs)-a new allotrope of carbon formed by rolling up Kagome graphene, and investigate this material using specialized first principles calculations. We identify two principal varieties of CKNTs-armchair and zigzag, and find both varieties to be stable at room temperature, based on ab initio molecular dynamics simulations. CKNTs are metallic and feature dispersionless states (i.e., flat bands) near the Fermi level throughout their Brillouin zone, along with an associated singular peak in the electronic density of states. We calculate the mechanical and electronic response of CKNTs to torsional and axial strains, and show that CKNTs appear to be more mechanically compliant than conventional carbon nanotubes (CNTs). Additionally, we find that the electronic properties of CKNTs undergo significant electronic transitions-with emergent partial flat bands and tilted Dirac points-when twisted. We develop a relatively simple tight-binding model that can explain many of these electronic features. We also discuss possible routes for the synthesis of CKNTs. Overall, CKNTs appear to be unique and striking examples of realistic elemental quasi-one-dimensional materials that may display fascinating material properties due to strong electronic correlation. Distorted CKNTs may provide an interesting nanomaterial platform where flat band physics and chirality induced anomalous transport effects may be studied together.
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Head and neck malignancies are the seventeenth most common malignancies, worldwide and second most common malignancy in India. So current study aims to compare between molecular marker p53 analysis and HPE for tumour positivity in primary resected margins in head and neck SCC. 61 patients with head and neck SCC were included in this prospective observational cross-sectional study performed in tertiary care hospital. A detailed history general physical examination blood investigation was done before the surgery. After the surgery, primary lesion from the resected tumour was sent for HPE analysis. From the same specimen, the margins at distance of 0.5-1 cm from primary tumour were sent for p53 mutation analysis. Report of p-53 mutation was noted and entered to the Performa. In our study we found out that in PDSCC HPE negative margins were found positive for p53 mutation in 81% cases. Which suggest that evaluation for p53 mutation should be done in PDSCC cases for HPE negative margins with in 1 cm. In patients of head and neck squamous cell carcinoma with free margins on HPE p-53 mutation is significantly associated to the PDSCC and margin upto 0.7 mm so recommended for p-53 profile can be beneficial in cases of the PDSCC and margins up to 0.7 mm for further management or for possibility of recurrence and its management to improve patients survival and decrease morbidity and mortality.
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PURPOSE: To study the outcomes of minor salivary gland transplantation for severe dry eye disease secondary to chronic Steven Johnson Syndrome. METHODS: It was an ambispective, interventional case series conducted at Rajendra Prasad Centre for Ophthalmic Sciences, Delhi, India from 2022 to 2023 evaluating the outcomes of minor salivary gland transplantation with anchorage of the minor salivary glands to superior rectus muscle in twenty cases of severe dry eye disease secondary to chronic Steven-Johnson Syndrome. The pre-operative clinical parameters were compared to those at post-operative 1 year follow-up. RESULTS: At 1 year follow-up, there was an improvement in mean Schirmer-1 value (p=0.0004), hyperemia score (p=0.0004), keratinization score (p=0.04), corneal epithelial defect score (p=0.0004), corneal opacification score (p=0.001), corneal neovascularization score (p=0.001), palisades of Vogt score (p=0.007), corneal keratinization score (p=0.04) and corneal conjunctivalization score (p=0.08). CONCLUSION: The minor salivary gland transplantation is a viable management option for cases with severe dry eye disease secondary to chronic Steven Johnson Syndrome with clinical improvement in corneal and conjunctival parameters of the ocular surface.
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Background: Lateral elbow tendinopathy is one of the most common chronic and degenerative diseases which significantly affects quality of life and the activities of daily living of a person. The following is a systematic review reporting a comparison between physical therapy intervention and corticosteroid injection for the treatment of lateral elbow tendinopathy. Method: PubMed, Web of Science, and Embase were searched using headings related to treatment options for Lateral elbow tendinopathy. The following keywords were used: lateral epicondylitis, physical therapy, and corticosteroid injection. Result: We descriptively analyzed and reviewed a total of 12 studies including a total of 1253 patients for lateral elbow tendinopathy. The physical therapy intervention included interventions like electrotherapy, manual therapy, and exercise. The studies included had an overall low to unknown risk of bias. Conclusion: Our review suggests corticosteroid injection provides beneficial short-term effects and physical therapy interventions provide intermediate to long-term effects, less additional treatment and low recurrence rate in patients with lateral elbow tendinopathy. Although high-quality randomized control trials are required in order to have a better understanding of both intervention types.
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Purpose: The round window approach has become the most preferred route for electrode insertion in cochlear implant surgery; however, it is not possible at times due to difficult round window membrane (RWM) visibility. Our study aims to investigate the relationship between preoperative radiological parameters and the surgical visibility of the RWM in Cochlear implant patients. Methodology: A prospective cross-sectional study of 31 patients, age < 6 years, with bilateral severe to profound sensorineural hearing loss was conducted at a tertiary care hospital. The preoperative HRCT temporal bone scan was studied, and the parameters evaluated were facial nerve location, facial recess width, and RWM visibility prediction. All patients were operated on via the posterior tympanotomy. The surgical RWM visibility was done after optimal drilling of the posterior tympanotomy recess. The relationship between the radiological parameters and surgical visibility of RWM was evaluated. Results: The difference in the facial nerve location as per the type of RWM was found to be significant (p value < 0.05). However, the facial recess width was not significantly associated with RWM visibility. The radiological prediction of RWM visibility by tracing the prediction line over RWM was significantly associated with intraoperative RWM visibility. Conclusion: The goal to look for preoperative scans is to predict the ease or difficulty of RWM visibility during surgery. The difficult visualization of the RWM, can result in dire intraoperative consequences. A comprehensive understanding of preoperative radiological parameters, coupled with meticulous surgical planning, is crucial to address these challenges effectively by focusing on enhancing RWM visualization.
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OBJECTIVE: To compare the diagnostic efficacy of multiplex polymerase chain reaction (PCR), Mycobacterium leprae-specific repetitive element (RLEP) PCR and loop-mediated isothermal amplification (LAMP) PCR in the diagnosis of pediatric leprosy as an alternative to slit-skin smear (SSS) examination. METHODS: A cross-sectional study was performed on 26 children aged 0-18 years with characteristic skin lesions of leprosy. SSS examination for acid fast bacilli (AFB) was performed for all children. Additionally, urine, stool and blood samples were tested by three PCR techniques - multiplex, RLEP and LAMP. The results of these tests were compared with each other and with results of SSS examination for acid fast bacilli (AFB) using appropriate statistical tests. RESULTS: Out of 26 patients studied, SSS examination was positive for AFB in 7 cases (26.9%). In blood samples, the positivity of multiplex PCR, RLEP PCR and LAMP PCR was 84.6%, 80.8%, and 80.8%, respectively. Multiplex PCR in blood samples was positive in 100% (n = 7) of SSS positive cases and 84.2% (16 out of 19) of the SSS negative cases (P < 0.001). The positivity of all PCR methods in urine and stool samples was significantly lesser than in blood. CONCLUSION: Multiplex PCR in blood sample is a superior diagnostic tool for pediatric leprosy compared to RLEP PCR and LAMP PCR as well as SSS examination.
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Fezes , Hanseníase , Reação em Cadeia da Polimerase Multiplex , Humanos , Criança , Hanseníase/diagnóstico , Estudos Transversais , Pré-Escolar , Adolescente , Lactente , Reação em Cadeia da Polimerase Multiplex/métodos , Masculino , Feminino , Fezes/microbiologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/normas , Mycobacterium leprae/isolamento & purificação , Mycobacterium leprae/genética , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/normas , Recém-Nascido , Sensibilidade e Especificidade , Técnicas de Diagnóstico MolecularRESUMO
The Mediator complex is essential for eukaryotic transcription, yet its role and the function of its individual subunits in plants, especially in rice, remain poorly understood. Here, we investigate the function of OsMED14_2, a subunit of the Mediator tail module, in rice development. Overexpression and knockout of OsMED14_2 resulted in notable changes in panicle morphology and grain size. Microscopic analysis revealed impact of overexpression on pollen maturation, reflected by reduced viability, irregular shapes, and aberrant intine development. OsMED14_2 was found to interact with proteins involved in pollen development, namely, OsMADS62, OsMADS63 and OsMADS68, and its overexpression negatively affected the expression of OsMADS68 and the expression of other genes involved in intine development, including OsCAP1, OsGCD1, OsRIP1, and OsCPK29. Additionally, we found that OsMED14_2 overexpression influences jasmonic acid (JA) homeostasis, affecting bioactive JA levels, and expression of OsJAZ genes. Our data suggest OsMED14_2 may act as a regulator of JA-responsive genes through its interactions with OsHDAC6 and OsJAZ repressors. These findings contribute to better understanding of the Mediator complex's role in plant traits regulation.
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Ciclopentanos , Regulação da Expressão Gênica de Plantas , Oryza , Oxilipinas , Proteínas de Plantas , Oryza/genética , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Reguladores de Crescimento de Plantas/metabolismo , Complexo Mediador/metabolismo , Complexo Mediador/genética , Pólen/crescimento & desenvolvimento , Pólen/genética , Pólen/metabolismoRESUMO
The present study covers the fabrication of flexible piezoelectric nanogenerators and their application towards sustainable power generation. The rod-like structure of erbium-doped ZnO (EZ) nanoparticles prepared by the hydrothermal synthesis route was successfully incorporated inside the polyvinylidene fluoride (PVDF) matrix using the solution casting method. Solution casting is an easy and cost-effective method for fabricating laminated, thin, flexible and lightweight EZ-PVDF nanocomposite films. The formation of the desired crystallographic phase of EZ-PVDF nanocomposite films and the presence of rod-like EZ nanoparticles inside the PVDF matrix were confirmed using X-ray diffraction and FESEM. The enhancement of the ß-phase fraction of the EZ-PVDF nanocomposite films as compared to bare PVDF was estimated using FTIR spectroscopy. The presence of a ferroelectric phase in the EZ-PVDF nanocomposite films was found due to the formation of a large area of interfaces between the EZ nanoparticles and the PVDF matrix. The maximum polarizations of 0.00696 µC cm-2 and 0.00683 µC cm-2 for two samples (EZP1 and EZP2, respectively) were observed at an electric field of 1.25 kV cm-1. The piezoelectric voltages were observed at relatively low frequencies for both nanocomposite films. The maximum piezoelectric voltages of 18.9 V and 15.5 V were observed at a 1 Hz frequency for EZP1 and EZP2, respectively. The output piezoelectric current of 16.88 mA and the maximum power density of 7773.68 W m-3 for EZP1 ensure its potential as an efficient piezoelectric nanogenerator with greater efficiency than those reported previously in published articles. The change in the piezoelectric voltage response of the nanocomposite films as a function of mechanical movement of human external body parts renders them the most suitable candidate for human-machine interfacing (HMI) applications, such as bending sensors and human motion sensors.