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BACKGROUND: Patients with hepatocellular carcinoma (HCC) and cirrhosis can present with features of severe portal hypertension, which can be worsened further by portal vein tumoral thrombosis (PVTT). Due to the technical difficulties and short survival of these patients, HCC was traditionally considered a relative contra-indication for transjugular intrahepatic portosystemic shunt (TIPS). However, there is an increasing body of evidence, mainly from China, supporting the use of TIPS in HCC. The present study aimed at analyzing the efficacy and safety of TIPS in patients with HCC. METHODS: From 2000 through May 2023, MEDLINE, Embase and Scopus were searched for studies analyzing the outcome of TIPS in HCC. Technical and clinical success, adverse events (AE) and mortality were the main outcomes assessed. With the use of a random effects model, the event rates were combined. RESULTS: Total 19 studies with 1498 patients were included in the final analysis. The pooled technical and clinical success rates with TIPS in HCC were 98.8% (98.0-99.7) and 94.1% (91.2-97.0), respectively. After TIPS, ascites was controlled in 89.2% (85.1-93.3) of the cases, while rebleeding was observed in 17.2% (9.4-25.0) of cases on follow-up. The pooled incidence of overall AE, serious AE and post-TIPS hepatic encephalopathy (HE) was 5.2% (2.5-7.9), 0.1% (0.0-0.4) and 25.1% (18.7-31.5), respectively. On follow-up, 11.9% (7.8-15.9) of the patients developed shunt dysfunction requiring re-intervention. CONCLUSION: The present analysis supports the feasibility, safety and efficacy of TIPS in the management of portal hypertension in patients with HCC.
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The identification of a wide variety of RNA molecules using high-throughput sequencing techniques in the transcriptome pool of living organisms has revealed hidden regulatory insights in the cell. The class of non-coding RNA fragments produced from transfer RNA, or tRFs, is one such example. They are heterogeneously sized molecules with lengths ranging between 15 and 50 nt. They have a history of being dysregulated in human malignancies and other illnesses. The detection of these molecules has been made easier by a variety of bioinformatics techniques. The various types of tRFs and how they relate to cancer are covered in this chapter. It also provides a summary of the biological significance of tRFs reported in human cancer. Additionally, it emphasizes the utilities of databases and computational tools that have been created by different research teams for the investigation of tRFs. This will further aid the exploration and analysis of tRFs in cancer research and will support future advancement and a better comprehension of these molecules.
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Biomarcadores Tumorais , Biologia Computacional , Neoplasias , RNA de Transferência , Humanos , RNA de Transferência/genética , RNA de Transferência/metabolismo , Biomarcadores Tumorais/genética , Neoplasias/genética , Neoplasias/metabolismo , Biologia Computacional/métodos , Simulação por Computador , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Low-pressure pneumoperitoneum (LPP) is an attempt to improve laparoscopic surgery. Lower pressure causes lesser inflammation and better hemodynamics. There is a lack of literature comparing inflammatory markers in LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB in laparoscopic cholecystectomy. METHODOLOGY: This was a single institutional prospective randomized control trial. Participants included all patients undergoing laparoscopic cholecystectomy for symptomatic gall stone disease. Participants were divided into 2 groups group A and B. Group A-Low-pressure group in which pneumoperitoneum pressure was kept low (8-10 mmHg) with deep Neuromuscular blockade (NMB) and Group B-Normal pressure group (12-14 mmHg) with moderate NMB. A convenience sample size of 80 with 40 in each group was selected. Lab investigations like CBC, LFT, RFT and serum IL-1, IL-6, IL-17, TNF alpha levels were measured at base line and 24 h after surgery and compared using appropriate statistical tests. Other parameters like length of hospital stay, post-operative pain score, conversion rate (low-pressure to standard pressure), and complications were also compared. RESULTS: Eighty participants were analysed with 40 in each group. Baseline characteristics and investigations were statistically similar. Difference (post-operative-pre-operative) of inflammatory markers were compared between both groups. Numerically there was a slightly higher rise in most of the inflammatory markers (TLC, ESR, CRP, IL-6, TNFα) in Group B compared to Group A but not statistically significant. Albumin showed significant fall (p < 0.001) in Group B compared to Group A. Post-operative pain was also significantly less (p < 0.001) in Group A compared to Group B at 6 h and 24 h. There were no differences in length of hospital stay and incidence of complications. There was no conversion from low-pressure to standard pressure. CONCLUSION: Laparoscopic cholecystectomy performed under low-pressure pneumoperitoneum with deep NMB may have lesser inflammation and lesser post-operative pain compared to standard pressure pneumoperitoneum with moderate NMB. Future studies with larger sample size need to be designed to support these findings.
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Biomarcadores , Colecistectomia Laparoscópica , Bloqueio Neuromuscular , Pneumoperitônio Artificial , Humanos , Colecistectomia Laparoscópica/métodos , Pneumoperitônio Artificial/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Biomarcadores/sangue , Bloqueio Neuromuscular/métodos , Cálculos Biliares/cirurgia , Pressão , Dor Pós-Operatória/etiologia , Tempo de Internação/estatística & dados numéricos , IdosoRESUMO
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is a significant cause of morbidity and mortality, especially in patients with chronic liver disease. As a reflection of geographical variations in India, there is significant variation in the prevalence and etiological factors of HCC. In contrast to previous studies reporting viral hepatitis as the most common etiology, recent data indicates a changing etiological pattern of cirrhosis and HCC, with alcohol and metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as the foremost cause. Thus, there was a need for an updated review of the current literature and databases for the changing epidemiology and etiological spectrum of HCC in India. The review included data primarily from the National Cancer Registry Program and the Global Burden of Diseases, Injuries, and Risk Factors Study, with the inclusion of other studies from India. The highlights of the present review are summarized in the following lines. Although the current incidence (2.15 per 100,000), prevalence (2.27 per 100,000), and mortality (2.21 per 100,000) rate of HCC in India remain lower compared to the global data, the annual rates of change in these parameters are higher in India. Among Indians, the present incidence, prevalence, and mortality related to HCC are higher in males, while the annual rate of change is higher in females. The Northeastern states have higher incidence, prevalence, and mortality related to HCC, but the Western states of Gujarat, Maharashtra, Goa, and Kerala are emerging as newer hotspots with higher annual rates of change in incidence, prevalence, and mortality. The incidence of HCC related to hepatitis B is on a downtrend, while those related to alcohol and MASLD are rising. Public health initiatives, awareness campaigns, and focused treatments are all necessary to combat these changes, particularly in areas with high incidence rates.
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Background and aims: Partial splenic artery embolization (PSAE) is an alternative treatment modality for managing hypersplenism secondary to portal hypertension. We are presenting a case series of patients with portal hypertension who underwent PSAE for symptomatic hypersplenism. Methods: We included patients with portal hypertension who underwent PSAE from January 2022 to December 2022. Patients' characteristics and procedure related complications were noted. Data were analyzed for improvement in the hematological parameters. Results: A total of 11 (7 women, median age 34 [18-56] years) patients were included. Three patients were cirrhotic (hepatitis B-2, metabolic dysfunction-associated steatotic liver disease -1) and 8 were non-cirrhotic (extra-hepatic portal vein obstruction-5, Non cirrhotic portal fibrosis-3). Splenic artery aneurysm was concomitantly present in 5 cases. Technical success was achieved in all cases. Post embolization, hemoglobin, white blood cells and platelet counts improved at 4 weeks, 12 weeks and 24 weeks along with symptomatic improvement. All patients had post-embolization syndrome. One patient developed transient ascites and secondary bacterial peritonitis which was managed conservatively. One patient died due to splenic abscess and septicemia. Conclusion: Although, hematological parameters and symptoms improve post procedure, PSAE is associated with major complications and should be performed judiciously in selected cases only. Graphical abstract is presented in Figure 1.
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Peptide- and protein-based therapeutics are becoming a promising treatment regimen for myriad diseases. Toxicity of proteins is the primary hurdle for protein-based therapies. Thus, there is an urgent need for accurate in silico methods for determining toxic proteins to filter the pool of potential candidates. At the same time, it is imperative to precisely identify non-toxic proteins to expand the possibilities for protein-based biologics. To address this challenge, we proposed an ensemble framework, called VISH-Pred, comprising models built by fine-tuning ESM2 transformer models on a large, experimentally validated, curated dataset of protein and peptide toxicities. The primary steps in the VISH-Pred framework are to efficiently estimate protein toxicities taking just the protein sequence as input, employing an under sampling technique to handle the humongous class-imbalance in the data and learning representations from fine-tuned ESM2 protein language models which are then fed to machine learning techniques such as Lightgbm and XGBoost. The VISH-Pred framework is able to correctly identify both peptides/proteins with potential toxicity and non-toxic proteins, achieving a Matthews correlation coefficient of 0.737, 0.716 and 0.322 and F1-score of 0.759, 0.696 and 0.713 on three non-redundant blind tests, respectively, outperforming other methods by over $10\%$ on these quality metrics. Moreover, VISH-Pred achieved the best accuracy and area under receiver operating curve scores on these independent test sets, highlighting the robustness and generalization capability of the framework. By making VISH-Pred available as an easy-to-use web server, we expect it to serve as a valuable asset for future endeavors aimed at discerning the toxicity of peptides and enabling efficient protein-based therapeutics.
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Proteínas , Proteínas/metabolismo , Proteínas/química , Aprendizado de Máquina , Bases de Dados de Proteínas , Biologia Computacional/métodos , Humanos , Peptídeos/toxicidade , Peptídeos/química , Simulação por Computador , Algoritmos , SoftwareRESUMO
HIV is a disease which reduces human resistant to fight. When our immunity becomes so weak that we are not able to fight even the common commensals of our body, this leads to what is called as an opportunistic infection. Tuberculosis is one of those most common type of opportunistic infection and in this pulmonary tuberculosis is more common. Extrapulmonary tuberculosis with HIV is the area of lesser research. In this study we tried to prove the Prevalence of extrapulmonary tuberculosis in AIDS patients and also the effect of combined HAART and ATT on prevalence of extrapulmonary tuberculosis and also its effect on Quality of life of the patient. This is a retrospective study conducted in a tertiary centre in the Department of Otorhinolaryngology & head and neck surgery from January 2020 to December 2020. A total of 80 patients were studied for 1 year. Confirmed cases of AIDS with extra pulmonary tuberculosis in head and neck region were studied, keeping all ethical issues in mind and after complete treatment of ATT along with HAART. After treatment, a significant number of patients got resolved with EPTB and gave positive response on their quality of life. Not only pulmonary tuberculosis, extrapulmonary tuberculosis with HIV is on the rise nowadays. Combined treatment of both can help in decreasing prevalence of extrapulmonary tuberculosis and improves quality of life.
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The interleukin (IL)-22 cytokine can be protective or inflammatory in the intestine. It is unclear if IL-22 receptor (IL-22Ra1)-mediated protection involves a specific type of intestinal epithelial cell (IEC). By using a range of IEC type-specific Il22Ra1 conditional knockout mice and a dextran sulfate sodium (DSS) colitis model, we demonstrate that IL-22Ra1 signaling in MATH1+ cells (goblet and progenitor cells) is essential for maintaining the mucosal barrier and intestinal tissue regeneration. The IL-22Ra1 signaling in IECs promotes mucin core-2 O-glycan extension and induces beta-1,3-galactosyltransferase 5 (B3GALT5) expression in the colon. Adenovirus-mediated expression of B3galt5 is sufficient to rescue Il22Ra1IEC mice from DSS colitis. Additionally, we observe a reduction in the expression of B3GALT5 and the Tn antigen, which indicates defective mucin O-glycan, in the colon tissue of patients with ulcerative colitis. Lastly, IL-22Ra1 signaling in MATH1+ progenitor cells promotes organoid regeneration after DSS injury. Our findings suggest that IL-22-dependent protective responses involve O-glycan modification, proliferation, and differentiation in MATH1+ progenitor cells.
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Colite , Sulfato de Dextrana , Interleucina 22 , Interleucinas , Receptores de Interleucina , Animais , Interleucinas/metabolismo , Camundongos , Glicosilação , Colite/metabolismo , Colite/patologia , Colite/induzido quimicamente , Receptores de Interleucina/metabolismo , Mucinas/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Humanos , Transdução de Sinais , Camundongos Endogâmicos C57BL , Inflamação/patologia , Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos Knockout , Galactosiltransferases/metabolismo , Galactosiltransferases/genética , Células-Tronco/metabolismoRESUMO
The coronavirus disease 2019 (COVID-19) epidemic has evolved into an international public health concern. Its causing agent was SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), a lipid bilayer encapsulated virus. Lipids have relevance in the host's viral cycle; additionally; viruses have been speculated to manipulate lipid signaling and production to influence the lipidome of host cells. SARS-CoV-2 engages the host lipid pathways for replication, like fatty acid synthesis activation via upregulation of AKT and SREBP pathway and inhibiting lipid catabolism by AMPK and PPAR deactivation. Consequently, lipoprotein levels are altered in most cases, i.e., raised LDL, TG, VLDL levels and reduced HDL levels like a hyperlipidemic state. Apo lipoproteins, a subsiding structural part of lipoproteins, may also impact viral spike protein binding to host cell receptors. In a few studies conducted on COVID-19 patients, maintaining Apo lipoprotein levels has also shown antiviral activity against SARS-CoV-2 infection. It was speculated that several potent hypolipidemic drugs, such as statins, hydroxychloroquine, and metformin, could be used as add-on treatment in COVID-19 management. Nutraceuticals like Garlic, Fenugreek, and vinegar have the potency to lower the lipid capability acting via these pathways. A link between COVID-19 and post-COVID alteration in lipoprotein levels has not yet been fully understood. In this review, we try to look over the possible modifications in lipid metabolism due to SARS-CoV-2 viral exposure, besides the prospect of focusing on the potential of lipid metabolic processes to interrupt the viral cycle.
Viral infection mainly alters the lipid profile similar to the hyperlipidemia state.SARS-CoV infection affects cell lipidome by promoting lipid anabolism through AKT and SREBP pathways.Viral infection also inhibits lipid metabolism via AMPK and PPAR signaling pathways.Nutraceuticals could be a potent antiviral agent by targeting the lipid transduction mechanisms and maintaining cell lipidome.
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We studied the electronic properties of a high-temperature superconductor in proximity to a ferromagnetic material in a bilayer film of La0.67Sr0.33MnO3 (LSMO)/YBa2Cu3O7 (YBCO). High-quality single-crystalline films of YBCO and LSMO/YBCO were grown epitaxially on an SrTiO3 (001) surface. Magnetization data of the LSMO/YBCO bilayer exhibit ferromagnetic transition at about 255 K, which is much smaller than the Curie temperature of bulk LSMO. Experimental data show the emergence of magnetic anisotropy with cooling, which becomes significantly stronger in the superconducting phase. The onset temperature of diamagnetism is observed at 86 K in the YBCO sample for the out-of-plane magnetization and at 89 K in the in-plane data. Interestingly, the diamagnetism sets in at about 86 K for both magnetization directions in the LSMO/YBCO film despite the presence of the ferromagnetic LSMO layer underneath. Ba 4d and Y 3d core-level spectra show different surface and bulk electronic structures. Surface contribution is reduced significantly in the LSMO/YBCO sample, suggesting enhanced bulk-like behavior due to an enhancement of electron density near the surface arising from charge transfer across the interface. These results reveal an outstanding platform for on-demand tuning of properties without affecting the superconductivity of the system for the exploration of fundamental science and applications in advanced technology.
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Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. In the brain, no detectable viral RNA and minimal residential immune cell activation was observed in the surviving mice post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and gene expression levels associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent systemic T helper 1 prone cellular immune responses and strong sera neutralizing antibodies against Delta and Omicron variants months post-acute infection. Overall, our findings suggest that infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long-COVID patients and provides new insights into the role of systemic and brain residential immune factors in PASC pathogenesis.
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COVID-19 , Modelos Animais de Doenças , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Animais , COVID-19/imunologia , SARS-CoV-2/imunologia , Camundongos , Humanos , Encéfalo/virologia , Encéfalo/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , FemininoRESUMO
Consumers are concerned about employing green processing technologies and natural ingredients in different manufacturing sectors to achieve a "clean label" standard for products and minimize the hazardous impact of chemical ingredients on human health and the environment. In this study, we investigated the effects of gelatinized starch dispersions (GSDs) prepared from six plant sources (indica and japonica rice, wheat, corn, potatoes, and sweet potatoes) on the formulation and stability of oil-in-water (O/W) emulsions. The effect of gelatinization temperature and time conditions of 85-90 °C for 20 min on the interfacial tension of the two phases was observed. Emulsification was performed using a primary homogenization condition of 10,000 rpm for 5 min, followed by high-pressure homogenization at 100 MPa for five cycles. The effects of higher oil weight fractions (15-25% w/w) and storage stability at different temperatures for four weeks were also evaluated. The interfacial tension of all starch GSDs with soybean oil decreased compared with the interfacial tension between soybean oil and water as a control. The largest interfacial tension reduction was observed for the GSD from indica rice. Microstructural analysis indicated that the GSDs stabilized the O/W emulsion by coating oil droplets. Emulsions formulated using a GSD from indica rice were stable during four weeks of storage with a volume mean diameter (d4,3) of ~1 µm, minimal viscosity change, and a negative ζ-potential.
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Emulsões , Óleo de Soja , Amido , Água , Emulsões/química , Amido/química , Água/química , Óleo de Soja/química , Oryza/química , Gelatina/química , Temperatura , Tensão Superficial , Tamanho da PartículaRESUMO
Nucleot(s)ide analogues, the current antiviral treatments against chronic hepatitis B (CHB) infection, are non-curative due to their inability to eliminate covalently closed circular DNA (cccDNA) from the infected hepatocytes. Preclinical studies have shown that coumarin derivatives can effectively reduce the HBV DNA replication. We evaluated the antiviral efficacy of thirty new coumarin derivatives in cell culture models for studying HBV. Furanocoumarins Fc-20 and Fc-31 suppressed the levels of pre-genomic RNA as well as cccDNA, and reduced the secretion of virions, HBsAg and HBeAg. The antiviral efficacies of Fc-20 and Fc31 improved further when used in combination with the hepatitis B antiviral drug Entecavir. There was a marked reduction in the intracellular HBx level in the presence of these furanocoumarins due to proteasomal degradation resulting in the down-regulation of HBx-dependent viral genes. Importantly, both Fc-20 and Fc-31 were non-cytotoxic to cells even at high concentrations. Further, our molecular docking studies confirmed a moderate to high affinity interaction between furanocoumarins and viral HBx via residues Ala3, Arg26 and Lys140. These data suggest that furanocoumarins could be developed as a new therapeutic for CHB infection.
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Antivirais , DNA Circular , Furocumarinas , Vírus da Hepatite B , Complexo de Endopeptidases do Proteassoma , Transativadores , Proteínas Virais Reguladoras e Acessórias , Replicação Viral , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Vírus da Hepatite B/metabolismo , Replicação Viral/efeitos dos fármacos , Humanos , Transativadores/metabolismo , Transativadores/genética , DNA Circular/metabolismo , DNA Circular/genética , Proteínas Virais Reguladoras e Acessórias/metabolismo , Proteínas Virais Reguladoras e Acessórias/genética , Furocumarinas/farmacologia , Antivirais/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , DNA Viral/metabolismo , DNA Viral/genética , Regulação para Baixo/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Células Hep G2RESUMO
Background: Recent studies from both India and outside India have shown a change in the etiological profile of hepatocellular carcinoma (HCC). We aimed to analyze the etiological spectrum and changing trends of HCC etiology in India using a systematic review of current literature and meta-analysis. Methods: Electronic databases of PubMed/Medline, Scopus, and Embase were searched from inception to July 2023 for studies reporting the data on the etiology of HCC from India. The pooled proportions with 95% confidence interval were calculated using summative statistics. Results: A total of 60 studies (n = 12,327) were included in the final analysis. The pooled proportions of HCC cases with at least one positive and negative viral marker were 56.0 (49.5-62.6) and 43.1% (36.5-49.8), respectively. The pooled proportion of HCC cases with positive hepatitis B virus (HBV) markers was 41.0 (35.8-46.1), while those with positive markers for hepatitis C virus were 20.3 (17.0-23.6). The pooled proportion of cases with HCC with significant alcohol intake was 19.0% (15.6-22.4), and those related to nonalcoholic fatty liver disease (NAFLD) were 16.9% (12.1-21.7). Around 7.9% (5.8-10.0) of the cases had HCC with multiple etiologies. Subgroup analysis showed a significant variation with the location of the study based on zone. Meta-regression analysis based on publication year (1990-2023) showed a significant reduction in the proportion of cases with HBV and an increase in cases with NAFLD. In contrast, the proportion of cases with hepatitis C virus and alcohol did not change significantly. Conclusion: Viral hepatitis is the most common etiology of HCC in India, predominantly HBV. The proportions of cases with HCC related to NAFLD are increasing, and those related to HBV are declining.
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Background: In the popular fighting sport of boxing, opponents strike each other above the belt line in the face, chest, and belly. The physical parts most exposed are therefore the nose and eyes. In amateur boxing, fights go only three rounds - three minutes for men and one minute for women - with a one-minute break in between. They wear gloves, but the head protection used in the men's game has been removed by AIBA due to the high likelihood of concussion when using head protection. Because chronic ocular changes may take longer than the expected short-term effects, this study included at least 3 years of competitive sports participation. Study design and setting: Institutional-based cross-sectional study. Materials and methods: To evaluate ophthalmic outcomes, 200 eyes of 100 active amateur, adult, and competitive male boxers were studied. Results: Of the 100 boxers, 51 had ophthalmic changes in at least one eye, and 49 had normal eyes. The average age of boxers was 24.98 years. The average duration of boxing training was 7.04 years. Healed eyelid scars, subconjunctival hemorrhages, conjunctival papillae, traumatic mydriasis, posterior synechiae, angulation abnormalities, traumatic cataracts, lens subluxation, increased intraocular pressure, and peripapillary atrophy were observed on the ocular side. None of these could be attributed to boxing. Conclusion: Boxing-related eye injuries are common in India and the most common vision-threatening eye abnormalities include traumatic cataracts, lens subluxation, and angle abnormalities. Surprisingly, no macular lesions were found on physical examination and OCT. Additional studies with a larger number of boxers will be needed to evaluate and prevent clinical symptoms. All boxers should have a complete eye exam regularly. Abbreviations: AIBA = Association Internationale de Boxe Amateur, OCT = Optical Coherence Tomography.
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Catarata , Anormalidades do Olho , Traumatismos Oculares , Subluxação do Cristalino , Adulto , Humanos , Feminino , Masculino , Adulto Jovem , Estudos Transversais , Índia/epidemiologia , Traumatismos Oculares/diagnóstico , Traumatismos Oculares/epidemiologiaRESUMO
The Notch pathway is an evolutionarily conserved signaling system that is intricately regulated at multiple levels and it influences different aspects of development. In an effort to identify novel components involved in Notch signaling and its regulation, we carried out protein interaction screens which identified non-muscle myosin II Zipper (Zip) as an interacting partner of Notch. Physical interaction between Notch and Zip was further validated by co-immunoprecipitation studies. Immunocytochemical analyses revealed that Notch and Zip co-localize within same cytoplasmic compartment. Different alleles of zip also showed strong genetic interactions with Notch pathway components. Downregulation of Zip resulted in wing phenotypes that were reminiscent of Notch loss-of-function phenotypes and a perturbed expression of Notch downstream targets, Cut and Deadpan. Further, synergistic interaction between Notch and Zip resulted in highly ectopic expression of these Notch targets. Activated Notch-induced tumorous phenotype of larval tissues was enhanced by over-expression of Zip. Notch-Zip synergy resulted in the activation of JNK pathway that consequently lead to MMP activation and proliferation. Taken together, our results suggest that Zip may play an important role in regulation of Notch signaling.
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Proteínas de Drosophila , Proteínas de Membrana , Cadeias Pesadas de Miosina , Receptores Notch , Transdução de Sinais , Animais , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Receptores Notch/metabolismo , Receptores Notch/genética , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Asas de Animais/metabolismo , Asas de Animais/crescimento & desenvolvimento , Drosophila/metabolismo , Drosophila/genética , Fenótipo , Metaloproteinases da Matriz/metabolismo , Metaloproteinases da Matriz/genética , Proliferação de Células , Miosina Tipo II/metabolismo , Miosina Tipo II/genéticaRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of conditions, progressing from mild steatosis to advanced fibrosis. Sarcopenia, characterized by decreased muscle strength and mass, shares common pathophysiological traits with NAFLD. An association exists between sarcopenia and increased NAFLD prevalence. However, data on the prevalence of sarcopenia in NAFLD and its impact on the outcomes of NAFLD remain inconsistent. AIM: To analyze the prevalence and outcomes of sarcopenia in patients with NAFLD. METHODS: We conducted a comprehensive search for relevant studies in MEDLINE, Embase, and Scopus from their inception to June 2023. We included studies that focused on patients with NAFLD, reported the prevalence of sarcopenia as the primary outcome, and examined secondary outcomes, such as liver fibrosis and other adverse events. We also used the Newcastle-Ottawa scale for quality assessment. RESULTS: Of the 29 studies included, the prevalence of sarcopenia in NAFLD varied widely (1.6% to 63.0%), with 20 studies reporting a prevalence of more than 10.0%. Substantial heterogeneity was noted in the measurement modalities for sarcopenia. Sarcopenia was associated with a higher risk of advanced fibrosis (odd ratio: 1.97, 95% confidence interval: 1.44-2.70). Increased odds were consistently observed in fibrosis assessment through biopsy, NAFLD fibrosis score/body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes (BARD) score, and transient elastography, whereas the fibrosis-4 score showed no such association. Sarcopenia in NAFLD was associated with a higher risk of steatohepatitis, insulin resistance, cardiovascular risks, and mortality. CONCLUSION: This systematic review highlights the critical need for standardized diagnostic criteria and measurement methods for sarcopenia in NAFLD patients. The variability in study designs and assessment methods for sarcopenia and liver fibrosis may account for the inconsistent findings. This review demonstrates the multidimensional impact of sarcopenia on NAFLD, indicating its importance beyond liver-related events to include cardiovascular risks, mortality, and metabolic complications.