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Several studies have implicated obesity-induced macrophage-adipocyte cross-talk in adipose tissue dysfunction and insulin resistance. However, the molecular cues involved in the cross-talk of macrophage and adipocyte causing insulin resistance are currently unknown. Here, we found that a lipid-induced monokine cyclophilin-A (CyPA) significantly attenuates adipocyte functions and insulin sensitivity. Targeted inhibition of CyPA in diet-induced obese zebrafish notably reduced adipose tissue inflammation and restored adipocyte function resulting in improvement of insulin sensitivity. Silencing of macrophage CyPA or pharmacological inhibition of CyPA by TMN355 effectively restored adipocytes' functions and insulin sensitivity. Interestingly, CyPA incubation markedly increased adipocyte inflammation along with an impairment of adipogenesis, however, mutation of its cognate receptor CD147 at P309A and G310A significantly waived CyPA's effect on adipocyte inflammation and its differentiation. Mechanistically, CyPA-CD147 interaction activates NF-κB signaling which promotes adipocyte inflammation by upregulating various pro-inflammatory cytokines gene expression and attenuates adipocyte differentiation by inhibiting PPARγ and C/EBPß expression via LZTS2-mediated downregulation of ß-catenin. Moreover, inhibition of CyPA or its receptor CD147 notably restored palmitate or CyPA-induced adipose tissue dysfunctions and insulin sensitivity. All these results indicate that obesity-induced macrophage-adipocyte cross-talk involving CyPA-CD147 could be a novel target for the management of insulin resistance and type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Tecido Adiposo/metabolismo , Animais , Ciclofilina A/genética , Ciclofilinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/metabolismo , Resistência à Insulina/genética , Lipídeo A/metabolismo , Camundongos , Monocinas/metabolismo , Obesidade/metabolismo , Peixe-Zebra/genéticaRESUMO
Glass/glass (G/G) photovoltaic modules are quickly rising in popularity, but the durability of modern G/G packaging has not yet been established. In this work, we examine the interfacial degradation modes in G/G and glass/transparent backsheet modules under damp heat (DH) with and without system bias voltage, comparing emerging polyolefin elastomer (POE) and industry-standard poly(ethylene-co-vinyl acetate) (EVA) encapsulants. We investigate the transport of ionic species at cell/encapsulant interfaces, demonstrating that POE limits both sodium and silver ion migration compared with EVA. Changes to the chemical structures of the encapsulants at the cell/encapsulant interfaces demonstrate that both POE and EVA are more susceptible to degradation in modules with a transparent backsheet than in the G/G configuration. Adhesion testing reveals that POE and EVA have comparable critical debond energies after the DH exposures regardless of system bias polarity. The results of this study indicate that the interfacial degradation mechanisms of G/G appear to be similar to those of conventional glass/backsheet modules. For emerging materials, our results demonstrate that POE offers advantages over EVA but that transparent backsheets may accelerate encapsulant degradation due to increased moisture ingress when compared with the G/G structure.
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BACKGROUND & OBJECTIVES: Prescription patterns of guideline-directed medical therapy (GDMT) after coronary artery bypass surgery [coronary artery bypass graft (CABG)] and percutaneous coronary intervention (PCI) at hospital discharge are often not optimal. In view of scarce data from the developing world, a retrospective analysis of medication advice to patients following CABG and PCI was conducted. METHODS: Records of 5948 patients (post-PCI: 5152, post-CABG: 796) who underwent revascularization from 2010 to 2014 at a single tertiary care centre in north India were analyzed. RESULTS: While age and gender distributions were similar, diabetes and stable angina were more frequent in CABG group. Prescription rates for aspirin 100 per cent versus 98.2 per cent were similar, while beta-blockers (BBs, 95.2 vs 90%), statins (98.2 vs 91.6%), angiotensin-converting enzyme inhibitors (89.4 vs 41.4%), nitrates (51.2 vs 1.1%) and calcium channel blockers (6.6 vs 1.6%) were more frequently prescribed following PCI. Despite similar baseline left ventricular ejection fraction (48.1 vs 51.1%), diuretics were prescribed almost universally post-CABG (98.2 vs 10.9%, P<0.001). Nearly all (94.4%) post-CABG patients received a prescription for clopidogrel. Patients undergoing PCI were much more likely to receive higher statin dose; 40-80 mg atorvastatin (72 vs <1%, P<0.001) and a higher dose of BB. INTERPRETATION & CONCLUSIONS: Significant differences in prescription of GDMT between PCI and CABG patients existed at hospital discharge. A substantial proportion of post-CABG patients did not receive BB and/or statins. These patients were also less likely to receive high-dose statin or optimal BB dose and more likely to routinely receive clopidogrel and diuretics. Such deviations from GDMT need to be rectified to improve quality of cardiac care after coronary revascularization.
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Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/cirurgia , Antagonistas Adrenérgicos beta , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia , Angioplastia Coronária com Balão/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Aspirina/uso terapêutico , Clopidogrel , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Prescrições de Medicamentos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Lacunas da Prática Profissional , Estudos Retrospectivos , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêuticoRESUMO
As endemic malaria is not commonly seen in the United States, most of the cases diagnosed and reported are associated with travel to and from the endemic places of malaria. As the number of imported cases of malaria has been increasing since 1973, it is important to look into these cases to study the morbidity and mortality associated with this disease in the United States. In this study, we would like to share our experience in diagnosing and treating these patients at our institution. We did a retrospective chart review of 37 cases with a documented history of imported malaria from 1998 to 2012. Among them, 16 patients had complicated malaria during that study period, with a mean length of hospital stay of 3.5 days. Most common place of travel was Africa, and chemoprophylaxis was taken by only 11% of patients. Travel history plays a critical role in suspecting the diagnosis and in initiating prompt treatment.
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Malária/diagnóstico , Malária/patologia , Viagem , Adulto , África , Idoso , Antimaláricos/uso terapêutico , Quimioprevenção/métodos , Quimioprevenção/estatística & dados numéricos , District of Columbia , Feminino , Hospitais de Ensino , Humanos , Malária/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Endothelial dysfunction may explain increased cardiovascular risk in patients with chronic kidney disease (CKD). METHODS: Brachial artery was imaged during reactive hyperemia (endothelium-dependent, flow-mediated dilatation, FMD) and during glyceryl trinitrate-mediated dilatation (nitroglycerine-mediated dilatation, NMD, endothelium-independent) in 108 patients with CKD and three months following renal transplantation (RT) in 60 of them. RESULTS: Patients with CKD had significantly lower FMD vs. controls (9.1% vs. 18.3%, p < 0.001) while NMD was comparable (19.8% vs. 21.8%, p = ns). Impaired FMD (<4.5%) was observed in 26.8% patients with CKD and was more common in those on hemodialysis (HD; 28.4% vs. 15.4%) vs. those not on dialysis. FMD for patients with glomerular filtration rate (GFR) 15-60 vs. <15 mL/min/1.73 m(2) was 12.9% and 8.8% (p = 0.05; respectively -29% and -52% lower vs. controls), indicating reduced FMD with increasing CKD severity. There was +72% increase in FMD following RT (9.1 to 15.7%, p < 0.001) while mean NMD was unchanged. Following RT, only 3.3% had impaired FMD. CONCLUSIONS: Patients with CKD have endothelial dysfunction as evidenced by reduced FMD. Decreased FMD indicating worsening endothelial function was noted with increasing severity of CKD. Within three months of RT, there was significant improvement in FMD, while NMD values did not change.
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Doenças Cardiovasculares/diagnóstico , Endotélio Vascular/patologia , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Insuficiência Renal Crônica/diagnóstico , Adulto , Idoso , Artéria Braquial/patologia , Doenças Cardiovasculares/etiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/cirurgia , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Differential release kinetics of cardiac biomarkers including brain natriuretic peptide (BNP), Troponin-I, and CK-MB following valve replacement (VR) are not well characterized. METHODS AND RESULTS: We serially measured these biomarkers 24 hours prior, six hours, 24 hours, 48 hours, and one month following mitral/aortic VR in 100 patients. Baseline BNP, Tn-I, and CK-MB levels were 304.01 pg/mL, 0.03 ng/mL, and 0.99 ng/mL, respectively. While BNP levels decreased at six hours, and then peaked at 24 hours, Tn-I and CK-MB levels increased within six hours and then showed declining trends by 24 hours. While Tn-I and CK-MB levels normalized at one month, 33% patients still had BNP >200 pg/mL. Those with baseline BNP >200 pg/mL more commonly had AF, higher RV systolic pressure, longer inotrope and ventilator duration, and longer mean ICU/hospital stay as compared to those with lower BNP, although echocardiographic left ventricular ejection fraction and Tn-I/CK-MB levels were similar. Inotrope duration >42 hours, ventilation time >29 hours, and ICU stay >4 days was seen in 42% versus 19%, 30% versus 9%, and 33% versus 14%, respectively, in those with BNP >/<200 pg/mL. Baseline BNP had a significant positive correlation with mean inotrope duration, ICU, and hospital stay. Baseline BNP was also a significant predictor of inotrope duration (odds ratio [OR]=5.9, 95% confidence interval [CI]=1.20-29.68, p=0.01) and ventilation time (OR=4.7, 95% CI=1.76-17.21, p=0.02). CONCLUSION: Release kinetics of cardiac biomarkers is significantly different following VR; BNP levels increase following an initial transient decline. Only BNP was a predictor of postoperative variables.
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Valva Aórtica/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Valva Mitral/cirurgia , Peptídeo Natriurético Encefálico/sangue , Adulto , Fibrilação Atrial , Biomarcadores/sangue , Creatina Quinase Forma MB/sangue , Feminino , Previsões , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Tempo de Internação , Masculino , Contração Miocárdica , Período Perioperatório , Prognóstico , Estudos Prospectivos , Respiração Artificial , Volume Sistólico , Sístole , Fatores de Tempo , Troponina I/sangue , Função Ventricular Esquerda , Adulto JovemRESUMO
BACKGROUND: Cyclical mastalgia, which is characterized by cyclic breast pain associated with the menstrual cycle, is a common condition among premenopausal women. Despite their prevalence, effective treatment options remain limited. Evening primrose oil (EPO) and vitamin E have been proposed as potential therapies for cyclical mastalgia; however, their efficacy remains uncertain, particularly when used in combination. OBJECTIVE: This study aimed to evaluate the efficacy of EPO, vitamin E, and their combination in alleviating breast pain associated with cyclical mastalgia through a randomized controlled trial. METHODS: Premenopausal women (n=126) with cyclical mastalgia were recruited from gynecology clinics and randomized to receive EPO (1000 mg twice daily), vitamin E (400 mg once daily), their combination, or a placebo for six months. Randomization was performed using computer-generated random numbers. Participants were assessed at baseline and monthly intervals for six months. The primary outcome was the change in breast pain severity measured using a validated pain questionnaire such as the short-form McGill Pain Questionnaire. The secondary outcomes included changes in breast pain characteristics, adverse effects, and treatment adherence. RESULTS: A total of 126 participants participated in this study. The combination of EPO and vitamin E demonstrated superior efficacy in reducing breast pain severity compared with individual treatments and placebo (p < 0.001). Participants in the combination group experienced a mean reduction in breast pain severity of 4.5 points on the pain scale, whereas those in the EPO and vitamin E groups experienced reductions of 2.5 and 3.0 points, respectively. Both EPO and vitamin E alone also showed significant improvements compared with placebo (p < 0.05), with mean reductions in breast pain severity of 2.0 and 2.5 points, respectively. Adverse effects were minimal and comparable across the treatment groups. CONCLUSION: Combination therapy with EPO and vitamin E appears to be an effective treatment option for cyclical mastalgia, offering superior pain relief compared with individual treatments and placebo.
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BACKGROUND: As surgery is an essential aspect of healthcare around the globe, it is necessary to consider complications related to it. Therefore, this study was conducted to evaluate the impact of the World Health Organization Surgical Safety Checklist (WHO SSC) on reducing the incidence of postoperative complications Methods: This single-center, prospective, comparative study was conducted at the Department of Gynecology and Obstetrics in a government hospital in Patna, Bihar. To assess the efficacy of the WHO SSC, the patients were divided into two groups, in which one group undergoing surgery was assessed with the checklist, and the other group was not. The rates of surgery-related complications were then compared in both groups. RESULTS: Our results showed a reduction in surgery-related complications in patients assessed with the WHO SSC. No statistically significant difference in duration of surgery was found between the groups. However, a statistically significant difference was observed in the rates of surgery-related complications between groups, especially in sepsis (p=0.0009), hemorrhage (p<0.0001), and infection at the site of surgery (p<0.0001). Mortality rates were not affected by the use of the SSC. CONCLUSION: The WHO SSC is a simple yet effective tool for reducing postoperative complications by improving communication between the various team members working in the operation theatre, although it has no effect on reducing mortality. Further research is needed to enhance its successful implementation and ensure its sustained use.
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INTRODUCTION: Erectile dysfunction (ED) and coronary artery disease (CAD) often share common risk factors, and there is growing evidence that ED might serve as a clinical marker for cardiovascular disease. Despite rising trends of CAD in Asian Indians, limited data are available on the prevalence of ED and its correlation with CAD severity in such patients. AIM: To study the prevalence of ED in Asian Indian patients undergoing coronary angiography and to assess if the severity of ED correlates with angiographic severity of CAD. METHODS: In all patients undergoing coronary angiography, ED was assessed using the International Index of Erectile Function-5 questionnaire. MAIN OUTCOME MEASURES AND RESULTS: Among 175 male patients, ED was present in 70%; patients with ED had a higher incidence of multivessel CAD (80% vs. 36%, P 0.001), diffuse CAD (81% vs. 34%, P 0.001), and higher number of mean coronary vessels involved compared with those without ED. Those with severe ED had higher prevalence of multivessel CAD and higher number of mean coronary vessels involved compared with those with milder grades of ED. Onset of symptoms of ED preceded symptoms of CAD by a mean of 24.6 months in 84% of patients. The presence of severe ED was associated with a 21-fold higher risk of having triple-vessel disease (odds ratio [OR] 21.94, 95% confidence interval [CI] 3.41-141.09, P = 0.001) and an 18-fold higher risk of having diffuse angiographic CAD (OR 17.91, 95% CI 3.11-111.09, P = 0.001). CONCLUSION: Asian Indians with angiographic CAD frequently have ED; symptoms of ED precede that of CAD in most patients. Incidence of multivessel and diffuse CAD is significantly more common in patients with ED. It is important for physicians to be aware of the close relationship between the two conditions so that patients with ED can have optimal risk stratification for concomitant CAD whenever required.
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Doença da Artéria Coronariana/epidemiologia , Disfunção Erétil/epidemiologia , Idoso , Povo Asiático , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etnologia , Disfunção Erétil/diagnóstico , Disfunção Erétil/etnologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de RiscoRESUMO
AIM: Metabolic syndrome (MS) is associated with higher mortality and morbidity in the general population. However, the effect of MS and its individual components on clinical outcomes in non-diabetic peritoneal dialysis (PD) patients has not been widely studied in India. Our aim was to study the prevalence of MS in non-diabetic PD patients who were on PD for at least 3 months and to analyze the influence of MS and its individual components on clinical outcomes of these patients on subsequent follow up. METHODS: We prospectively included 163 non-diabetic PD patients (mean age 45.1 ± 16.2 years, 104 male). MS was defined using the modified National Cholesterol Education Programme (ATP III) criteria. Outcomes of patients with and without MS were compared. RESULTS: Of the 163 non-diabetic PD patients, 84 (51.5%) patients had MS. The mean follow up duration was 24.0 ± 14.0 patient months. Patients with MS had significantly greater body mass index (P = 0.007), Systolic BP (P = 0.001), diastolic BP (P = 0.001), Triglycerides (P = 0.002), total cholesterol (P = 0.001) level; and significantly lower high density lipoprotein (P = 0.013) values. Mean survival (patient-months) of patients with MS (30.7 (95%CI 27.1-34.3)) was significantly inferior to that of patients without MS (55.6 (95% CI 50.8-60.4), P = 0.001). Mean technique survival of patients with MS was also significantly lower (38.9 (95% CI 35.9-41.9)) compared to that of patients without MS (61.5 (95% CI 58.3-64.7), P = 0.039). On univariate Cox regression analysis diastolic BP (P = 0.003), Systolic BP (P = 0.026), hypertension (HTN) (P = 0.001) and MS (P = 0.001) were found to be independent predictors of mortality. However on multivariate Cox hazard regression analysis, only MS (HR 5.39 (95% CI 2.06-14.14), P = 0.001) was found to be the significant predictors of mortality in these patients. Among the factors other than components of MS, the presence of comorbidities (P = 0.029), serum albumin (P = 0.042), non-HDL cholesterol (P = 0.003), total cholesterol/HDL (P = 0.001) and MS (P = 0.001) were important factors predicting mortality on univariate Cox regression, while only MS (P = 0.001) and serum albumin (P = 0.013) were the independent factors predicting mortality on multivariate analysis. CONCLUSION: Prevalence of MS in non-diabetic PD patient is high and predicts long term patient and technique survival.
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Nefropatias/terapia , Síndrome Metabólica/epidemiologia , Diálise Peritoneal , Adulto , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Comorbidade , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Índia/epidemiologia , Estimativa de Kaplan-Meier , Nefropatias/diagnóstico , Nefropatias/mortalidade , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/mortalidade , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/epidemiologia , Razão de Chances , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/mortalidade , Prevalência , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Rapid development of anti-SARS-CoV-2 vaccinations in the late 2020s has significantly altered the trajectory in which the virus affects various patient demographics, especially the most susceptible ones. In light of ethical and conceptual safety considerations, pregnant women were initially barred from participating in clinical studies for the coronavirus disease 2019 (COVID-19) vaccination programs. However, the steady accumulation of reliable observational data from cohorts of pregnant women who received vaccinations enabled the research establishments to quickly address a number of open questions. Still, more than a year after vaccines were widely available, the safety concerns of expectant or nursing mothers are cited as the primary justification for refusing COVID-19 vaccination, and notably, the rate of vaccination in the said populations is known to be consistently lower than those of the general populace. In light of such a scenario, we have made an attempt to garner relevant studies that evaluated the effect of COVID-19 vaccination on pregnant and lactating mothers which may prove to be supporting evidence for its wide usage among the said population.
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Environmental factors are important causes that impair global pregnancy outcomes and are, importantly, responsible for maternal morbidity and mortality. However, apart from the direct reasons for maternal deaths, mainly obstetric and neonatal complications, such factors are ignored or given less importance. The recent surge in research on the impact of various environmental factors on pregnancy outcomes suggests the need for immediate attention to such factors and device-specific policies to counter the situation. Moreover, the recent coronavirus disease of 2019 (COVID-19) pandemic, global warming, and climate change showed a lack of preparedness to counter the impact of such events on maternal survival and safe and successful pregnancy outcomes. In the present review, we have emphasized the specific factors responsible for increased maternal and neonatal deaths and their association with specific environmental factors. Increased attention on maternal healthcare, preparedness to counter sudden environmental challenges and improvement of the conventional requirement for better maternal healthcare access and nutrition at a global level may improve the scenario.
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Visceral leishmaniasis (VL) is a severe form of leishmaniasis, primarily affecting the poor in developing countries. Although several studies have highlighted the importance of toll-like receptors (TLRs) in the pathophysiology of leishmaniasis, the role of specific TLRs and their binding partners involved in Leishmania donovani uptake are still elusive. To investigate the mechanism of L. donovani entry inside the macrophages, we found that the parasite lipophosphoglycan (LPG) interacted with the macrophage TLR4, leading to parasite uptake without any significant alteration of macrophage cell viability. Increased parasite numbers within macrophages markedly inhibited lipopolysachharide-induced pro-inflammatory cytokines gene expression. Silencing of macrophage-TLR4, or inhibition of parasite-LPG, significantly stemmed parasite infection in macrophages. Interestingly, we observed a significant enhancement of macrophage migration, and generation of reactive oxygen species (ROS) in the parasite-infected TLR4-silenced macrophages, whereas parasite infection in TLR4-overexpressed macrophages exhibited a notable reduction of macrophage migration and ROS generation. Moreover, mutations in the leucine-rich repeats (LRRs), particularly LRR5 and LRR6, significantly prevented TLR4 interaction with LPG, thus inhibiting cellular parasite entry. All these results suggest that parasite LPG recognition by the LRR5 and LRR6 of macrophage-TLR4 facilitated parasite entry, and impaired macrophage functions. Therefore, targeting LRR5/LRR6 interactions with LPG could provide a novel option to prevent VL.
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Leishmania donovani , Leishmaniose Visceral , Parasitos , Animais , Receptor 4 Toll-Like , Espécies Reativas de Oxigênio , MacrófagosRESUMO
Under the condition of chronic obesity, an increased level of free fatty acids along with low oxygen tension in the adipose tissue creates a pathophysiological adipose tissue microenvironment (ATenv), leading to the impairment of adipocyte function and insulin resistance. Here, we found the synergistic effect of hypoxia and lipid (H + L) surge in fostering adipose tissue macrophage (ATM) inflammation and polarization. ATenv significantly increased miR-210-3p expression in ATMs which promotes NF-κB activation-dependent proinflammatory cytokine expression along with the downregulation of anti-inflammatory cytokine expression. Interestingly, delivery of miR-210-3p mimic significantly increased macrophage inflammation in the absence of H + L co-stimulation, while miR-210-3p inhibitor notably compromised H + L-induced macrophage inflammation through increased production of suppressor of cytokine signaling 1 (SOCS1), a negative regulator of the NF-κB inflammatory signaling pathway. Mechanistically, miR-210 directly binds to the 3'-UTR of SOCS1 mRNA and silences its expression, thus preventing proteasomal degradation of NF-κB p65. Direct delivery of anti-miR-210-3p LNA in the ATenv markedly rescued mice from obesity-induced adipose tissue inflammation and insulin resistance. Thus, miR-210-3p inhibition in ATMs could serve as a novel therapeutic strategy for managing obesity-induced type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , MicroRNAs , Camundongos , Animais , NF-kappa B/metabolismo , MicroRNAs/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Tecido Adiposo/metabolismo , Citocinas/metabolismo , Hipóxia/metabolismo , Inflamação/metabolismo , Obesidade/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismoRESUMO
Increasing evidence supports vanillin and its analogs as potent toll-like receptor signaling inhibitors that strongly attenuate inflammation, though, the underlying molecular mechanism remains elusive. Here, we report that vanillin inhibits lipopolysaccharide (LPS)-induced toll-like receptor 4 activation in macrophages by targeting the myeloid differentiation primary-response gene 88 (MyD88)-dependent pathway through direct interaction and suppression of interleukin-1 receptor-associated kinase 4 (IRAK4) activity. Moreover, incubation of vanillin in cells expressing constitutively active forms of different toll-like receptor 4 signaling molecules revealed that vanillin could only able to block the ligand-independent constitutively activated IRAK4/1 or its upstream molecules-associated NF-κB activation and NF-κB transactivation along with the expression of various proinflammatory cytokines. A significant inhibition of LPS-induced IRAK4/MyD88, IRAK4/IRAK1, and IRAK1/TRAF6 association was evinced in response to vanillin treatment. Furthermore, mutations at Tyr262 and Asp329 residues in IRAK4 or modifications of 3-OMe and 4-OH side groups in vanillin, significantly reduced IRAK4 activity and vanillin function, respectively. Mice pretreated with vanillin followed by LPS challenge markedly impaired LPS-induced IRAK4 activation and inflammation in peritoneal macrophages. Thus, the present study posits vanillin as a novel and potent IRAK4 inhibitor and thus providing an opportunity for its therapeutic application in managing various inflammatory diseases.
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Lipopolissacarídeos , NF-kappa B , Animais , Camundongos , Inflamação/metabolismo , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
COVID-19 pandemic has been a major challenge for health care services all around the world. With increasing COVID-19 cases and lockdown enforcement, there has been a significant delay in the presentation of patients in the emergency department; also the fear in people of contracting COVID-19 from the hospital is an additional factor. The following case report describes such an incidence of delay in presentation of buccal fat pad injury patient to the emergency department.
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Objective The aim of this study was to determine the perinatal outcome of pregnant patients complicated with meconium-stained amniotic fluid (MSAF) compared with clear amniotic fluid. Methodology This prospective cross-sectional study was conducted in the Department of Obstetrics and Gynecology in collaboration with the Department of Pediatrics at Indira Gandhi Institute of Medical Sciences, Patna, India, from September 2016 to January 2018. A total of 200 patients were included in the study after taking their written consent. Out of these 200 patients, 100 patients had MSAF, and the other 100 patients with clear liquor were taken as controls after fulfilling the inclusion and exclusion criteria. These two groups of patients were compared regarding various maternal and neonatal parameters. These parameters were compared and tested statistically for significance. Results Among the 100 patients with MSAF, 20 patients had grade 1 meconium (X), 22 patients had grade 2 meconium (Y), and 58 patients had grade 3 meconium (Z). The majority of patients in the MSAF group were primigravida and more than 25 years of age. In addition, 47% of patients in the MSAF group had some associated high-risk factors and 50% of patients had non-reassuring fetal heart rate patterns, and among these, 39 patients had grade 3 MSAF (X). In the MSAF group, 49% of patients had undergone lower segment cesarean section (LSCS), whereas in the non-MSAF group, it was 37%. Also, 30% of babies in the MSAF group and 13% in the non-MSAF group had neonatal intensive care unit (NICU) admission; 22% of babies in the MSAF group and 12% of babies in the non-MSAF group had an adverse neonatal outcome. Meconium aspiration syndrome was present in 14% of the patients in the MSAF group, and among these, two babies had neonatal death and both had severe birth asphyxia. In the non-MSAF group, there was one neonatal death due to neonatal sepsis. However, after statistically analyzing the neonatal outcome in both the groups, there was no statistical difference between the two groups (p<0.001). Conclusion MSAF is associated with increased frequency of operative delivery, poor neonatal outcomes, and increased NICU admission. Management of labor with MSAF requires appropriate intrapartum care with continuous fetal heart rate monitoring, and this can reduce unnecessary cesarean sections in patients with MSAF.
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BACKGROUND: The pathophysiology of an atherosclerotic plaque is mediated by the mechanisms involving thrombus formation and systemic inflammation. While C-reactive protein (CRP) levels are useful in predicting a cardiovascular event in intermediate risk population, the usefulness of routinely measuring fibrinogen in patients with acute coronary syndrome (ACS) is debatable. Also, data on the association of these markers with periprocedural outcomes in patients undergoing percutaneous coronary interventions (PCI) is scarce. AIMS: The study aimed to determine whether the levels of fibrinogen and CRP vary across the different spectra of CAD and whether they have any correlation with cardiac Troponin I levels. MATERIALS AND METHODS: A total of 284 patients with coronary artery disease undergoing percutaneous coronary intervention were included in the study. Complete blood count, serum lipid profile, serum CRP, fibrinogen, and troponin I were measured for all patients. RESULTS: Patients with STEMI had significantly higher levels of CRP as compared to those with unstable angina (USA) and chronic stable angina (CSA). Patients presenting with ACS had significantly higher baseline fibrinogen as compared to those with CSA. A significant positive correlation between CRP and admission Troponin I (r = 0.50; P < 0.05) as well as fibrinogen and admission troponin I (r = 0.30; P < 0.05) was observed. The CRP levels were significantly higher in 15 patients with periprocedural MI as compared to those who did not develop periprocedural MI. CONCLUSIONS: : The levels of the markers of inflammation and atherothrombosis vary with presentation across varied spectra of CAD with generally higher levels in acute presentation and in those who develop periprocedural MI.
Assuntos
Biomarcadores , Proteína C-Reativa , Doença da Artéria Coronariana , Fibrinogênio , Intervenção Coronária Percutânea , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Fibrinogênio/metabolismo , Humanos , Troponina I/sangueRESUMO
Introduction: Hyperbilirubinemia is most common normal physiological phenomenon in neonates affecting almost one third of newborn.it may lead to neuro disability leading to deafness and cerebral palsy which can be prevented if detected and treated as soon as possible. Albumin is produced in seventh week of intrauterine life and it can be measured by cord blood and in this study we can establish serum albumin with neonatal hyperbilirubinemia and can be treated by phototherapy or exchange transfusion. Material and Method: The study consists of 55 randomly selected eligible term neonates delivered at Rajendra Institute of Medical sciences from March 2019 to August 2020. Conclusion: In this study, in term neonates, level of serum albumin in umbilical cord less than 2.8 g/dl has no correlation with occurrence significant hyperbilirubinemia, so a level <2.8 gm/dl of serum albumin in umbilical cord blood can be used as critical value indicator in triaging predict the risk of occurring of significant hyperbilirubinemia in term neonates.level >3.4 gm/dl is considered safe in neonates who are the candidates for early discharge in the absence of other risk factors.
RESUMO
Commercial backsheets based on polyvinylidene fluoride (PVDF) can experience premature field failures in the form of outer layer cracking. This work seeks to provide a better understanding of the changes in material properties that lead to crack formation and find appropriate accelerated tests to replicate them. The PVDF-based backsheet outer layer can have a different structure and composition, and is often blended with a poly(methyl methacrylate) (PMMA) polymer. We observed depletion of PMMA upon aging with sequential (MAST) and combined (C-AST) accelerated stress testing. In field-aged samples from Arizona and India, where PVDF crystallizes in its predominant α-phase, the degree of crystallinity greatly increased. MAST and C-AST protocols were, to some extent, able to replicate the increase in crystallinity seen in PVDF after ~ 7 years in the field, but no single-stress test condition (UV, damp heat, thermal cycling) resulted in significant changes in the material properties. The MAST regimen used here was too extreme to produce realistic degradation, but the test was useful in discovering weaknesses of the particular PVDF-based outer layer structure studied. No excessive ß-phase formation was observed after aging with any test condition; however, the presence of ß-phase was identified locally by Fourier transform infrared spectroscopy (FTIR). We conclude that both MAST and C-AST are relevant tests for screening outdoor failure mechanisms in PVDF backsheets, as they were successful in producing material degradation that led to cracking.