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Health proteins Corona Prevents Endosomal Break free of Functionalized DNA Nanostructures in Residing Tissue.
AIMS Chronic stress leads to the development of male sexual problems such as ejaculatory dysfunctions. The rhythmic contractions of vas deferens (VD) play an important role on the ejaculatory process. In the current study, we investigated whether infliximab (IFX) treatment has any beneficial effects on possible alterations in contractility of VD obtained from rats exposed to unpredictable chronic mild stress (UCMS). MATERIALS AND METHODS The rats were randomly divided into four groups control, control+IFX, UCMS and UCMS+IFX. PKM2 inhibitor in vivo IFX (5 mg/kg/week, i.p.) was administrated for 5 weeks during UCMS period. Depressive like-behaviors were evaluated using locomotor activity, forced swimming and sucrose consumption and preference tests. The blood was collected for serum biochemical determinations. VD tissues were harvested for functional studies and, measurements of oxidative stress, inflammatory and apoptotic biomarkers. KEY FINDINGS We observed increased serum concentration of corticosterone and depressive-like behaviors in rats exposed to UCMS. In VD tissues of UCMS-exposed rats, noradrenaline- and adenosine triphosphate (ATP)-induced contractile responses significantly enhanced and electrical field stimulation (EFS)-induced contractile responses markedly decreased. UCMS exposure induced inflammation, oxidative stress and apoptosis in VD. However, IFX treatment significantly improved all the aforementioned parameters. SIGNIFICANCE The results of the present study revealed that chronic stress-induced depression caused VD dysfunction by promoting inflammation and oxidative stress in VD. IFX protected against VD dysfunction through its anti-inflammatory and antioxidant effects. BACKGROUND Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by unbalanced proliferation and apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Prohibitin 1 (PHB1) is known for its significant anti-proliferative activity. However, the role of PHB1 in PASMCs and PAH have not been elucidated. METHODS Monocrotaline (MCT 60 mg/kg) was used to build a PAH model in SD rats. Right ventricular systolic pressure (RVSP) and right ventricle (RV) hypertrophy were measured. Morphology of pulmonary vessels was observed by Hematoxylin-Eosin (HE) staining. Expression of PHB1 in pulmonary arteries and PASMCs was determinated by immunoblot and immunofluorescence. Cell proliferation was detected by CCK8 and EDU when PASMCs were stimulated by PDGF-BB (20 ng/mL). Furthermore, siRNA for PHB1 and Akt inhibitor were conducted to investigate the mechanism behind the role of PHB1 and AKT signaling pathway in PASMCs proliferation and apoptosis. RESULTS The protein expression of PHB1 in PAH rats lung tissue was significantly up-regulated accompanied by elevated RVSP and enhanced RV hypertrophy. Immunohistochemistry showed that PHB1 was mainly localized in the pulmonary vascular smooth muscle layer. PDGF-BB significantly up-regulated the expression of PHB1 in rat primary PASMCs in a time- and dose-dependent manner. After PHB1 knock down, PASMCs proliferation was significantly suppressed while apoptosis was significantly recovered. Meanwhile the level of proliferating cell nuclear antigen (PCNA) and P-Akt were significantly down-regulated. Perifosine (Akt inhibitor) also significantly inhibit proliferation of PASMCs. CONCLUSION PHB1 contributes to pulmonary vascular remodeling by accelerating proliferation of PASMCs which involves AKT phosphorylation. Gastric cancer (GC) is responsible for high morbidity and mortality worldwide. This cancer claims fifth place among other cancers. There are a number of factors associated with GC development such as alcohol consumption and tobacco smoking. It seems that genetic factors play significant role in GC malignancy and progression. MicroRNAs (miRs) are short non-coding RNA molecules with negative impact on the expression of target genes. A variety of studies have elucidated the potential role of miRs in GC growth. Investigation of molecular pathways has revealed that miRs function as upstream modulators of Wnt signaling pathway. This signaling pathway involves in important biological processes such as cell proliferation and differentiation, and its dysregulation is associated with GC invasion. At the present review, we demonstrate that how miRs regulate Wnt signaling pathway in GC malignancy. OBJECTIVES Advance care planning in young-onset dementia largely remains a blind spot within current literature. This study aimed to explore the engagement in and the conceptualization of advance care planning from the perspective of family caregivers of persons with young-onset dementia and to identify potential similarities and differences in this area between American and Belgian persons with young-onset dementia and their family caregivers. DESIGN An exploratory qualitative study. SETTING AND PARTICIPANTS We purposively sampled adult family caregivers of persons with young-onset dementia; our respondents were 13 American and 15 Belgian caregivers with varying familial relationships to the patient. METHODS We conducted 28 semi-structured interviews, using the same interview guide for American and Belgian respondents. Verbatim transcripts were analysed through the method of constant comparative analysis. RESULTS Important similarities between American and Belgian respondents were restricted knowledge of advance care planning, limited communication about advance directives, and their recommendation for professionals to timely initiate advance care planning. Major differences were attention paid to those end-of-life decisions depicted in the legislature of their respective countries, American caregivers placed higher emphasis on financial planning than their Belgian peers, and, in the case of consulting professionals for advance directives, American caregivers turned to lawyers, whereas Belgian caregivers relied on physicians. CONCLUSIONS AND IMPLICATIONS Specific nuances and challenges in terms of advance care planning in young-onset dementia arise from a particular societal and legal context on the one hand, and from patients' and caregivers' younger age on the other. Professionals' awareness of and responsiveness to these specificities could facilitate the advance care planning process. Based on our interpretation of results, several recommendations for practice and policy are made. OBJECTIVES To identify clinical and/or functional variables predictive of successful oxygen-weaning among older patients affected by respiratory insufficiency undergoing pulmonary rehabilitation. DESIGN Retrospective study. SETTING AND PARTICIPANTS Data are from 154 patients aged 65 years and older (mean age = 78.1 years; female 50.6%) admitted to a pulmonary rehabilitation unit to follow an in-patient program. Patients must require oxygen therapy at admission. METHODS All patients performed the 6-Minute Walking Test at admission and before discharge as well as a spirometry at a steady state. Multivariate logistic regressions were performed to identify positive and negative predictors of successful oxygen weaning. RESULTS Successful oxygen weaning was obtained in 47 participants (30.5%). The restrictive pattern was associated with a 4-fold likelihood of successful oxygen weaning at the end of the rehabilitation program compared with the obstructive one. A positive association was also found for arterial oxygenation index (PaO2/FiO2 ratio) at baseline. A decreased likelihood of successful oxygen weaning was reported for the subjective dyspnea perception score at exertion evaluated with a modified Borg scale. CONCLUSIONS AND IMPLICATIONS The restrictive pattern, PaO2/FiO2 ratio, and modified Borg dyspnea scale score under exertion were significantly associated with successful oxygen-weaning. The identified predictors may support clinicians at precociously identifying patients who may not require oxygen therapy after discharge. Therefore, these findings would make it possible for clinicians to better tailor the rehabilitation program. Having a hepatitis B virus (HBV) or hepatitis C virus (HCV) infection places a child at higher risk for subsequent chronic hepatitis B (CHB) or chronic hepatitis C (CHC) infection. The risk of mother-to-child transmission is higher for HBV (20% to 90%) than for HCV ( less then 5%). Perinatal HBV infection generally causes CHB infection while perinatal HCV infection has a certain rate of spontaneous viral clearance (around 20% to 30%). Of the two, only HBV infection can benefit from passive/active perinatal immunoprophylaxis. The risk of CHB in children with HBV horizontal transmission decreases with age, whereas HCV transmission among teenagers commonly results into a long-life infection and CHC infection. Children with CHB or CHC should be carefully assessed for the need for antiviral treatment. When treatment cannot be deferred, pediatric CHB infection has different first-line treatment options standard interferon (for children aged≥1 year), pegylated interferon (for children aged≥3 years), and the oral nucleotide analogues entecavir (for children aged≥2 years) and tenofovir (for children aged≥12 years). The choice of treatment depends on the child's age, virus genotypes, previous treatment failure and presence of contraindications. Expected responsiveness rate is 25% of hepatitis B e-antigen clearance, with both standard interferon and nucleotide analogues. Direct antiviral agents are first-line treatment for CHC infection in children aged 3 years or older. Hepatitis C virus sustained virus response is as high as 97%. Therefore, if direct antiviral agents can be proven to be safe and well tolerated in very young children, HCV eradication could be planned after the first screening. OBJECTIVES Patient-reported cognitive complaint (CI) is poorly described in older adults with cancer. The purpose of this study was to quantify the prevalence and examine the associations of patient-reported CI in older adults with gastrointestinal (GI) malignancies at diagnosis. MATERIALS AND METHODS Using participants ≥60 years with GI malignancies from the Cancer & Aging Resilience Evaluation (CARE) Registry that underwent a Geriatric Assessment (GA), we examined CI using the Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form 4a Cognitive Function. Cognition scores were dichotomized into normal (scores of 15-20) and impaired (4-14), and bivariate and multivariate analyses were used to examine associations. RESULTS A total of 264 participants with GI malignancy were included, mean age of 70.0 ± 7.1, 55.7% male, pancreatic cancer was the most common cancer (24.2%) and majority were stage III/IV (68.2%). 29.3% of participants endorsed CI. CI was not associated with demographic and clinical domains, but was associated with many GA impairments including instrumental Activities of Daily Living (iADL) impairment (adjusted odds ratio [aOR] 6.0, 95% confidence interval 3.0-11.8), falls (aOR 2.7, 1.4-5.4), anxiety (aOR 10.3, 5.2-20.4), and depression (aOR 10.2, 5.2-20.4). CI was also associated with reduced global mental (aOR 18.7, 8.1-42.2) and physical (aOR 4.7, 2.4-8.9) quality of life, and prior hospitalizations (aOR 2.4, 1.2-4.8). CONCLUSION We found a high prevalence of patient-reported CI in older adults with GI malignancies that was associated with increased GA impairments, reduced health-related quality of life, and increased healthcare utilization. Published by Elsevier Ltd.
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