Discovery of a Remarkable Methyl Shift Effect in the Vanilloid Activity of Triterpene Amides

As part of a study on triterpenoid conjugates, the dietary pentacyclic triterpenoids oleanolic (2a) and ursolic acids (3a) were coupled with vanillamine, and the resulting amides (2b and 3b, respectively) were assayed for activity on the vanilloid receptor TRPV1. Despite a structural difference limited to the location of a methyl group in their conformationally rigid pentacyclic core, oleanoloyl vanillamide dramatically outperformed ursoloyl vanillamide in terms of potency (EC50 = 35 ± 2 nM for 2b and 5.4 ± 2.3 μM for 3b). Using molecular docking and dynamics, this difference was translated into distinct accommodation modes at the TRPV1 vanillyl ligand pocket, suggesting a critical role of a C-H πphenyl interaction between the triterpenoid C-29 methyl and Phe591 of TRPV1. Because the molecular mechanisms underlying the activation process of transient receptor channels (TRPs) remain to be fully elucidated, the observation of spatially restricted structure-activity information is of significant relevance to identify the molecular detail of TRPV1 ligand gating

Parentification, distress, and relationship with parents as factors shaping the relationship between adult siblings and their brother/sister with disabilities

According to parentification theory, when the siblings of a brother/sister with disabilities assume parent-like duties, this role reversal is known as sibling-focused parentification. It has a significant impact on these siblings’ distress and the quality of their family relationships; 605 Italian adult siblings (19–26 years) of people with disabilities completed the online survey. Measures of siblings’ parentification, distress, quality of family relationships, social support, and perceived benefits of parentification were used. The hypothesized model aims to test, on the target sample, the distress and the quality of the relationship with parents as mediators on the interplay between the siblings’ parentification and their sibling relationship. Additionally, social support and perceived benefits of parentification as protective factors were considered. Results showed that the distress and the low quality of the relationship with parents negatively affected the interplay between the siblings’ parentification and the relationship with their own brother/sister with disabilities. Social support and the perceived benefits of parentification decreased the siblings’ distress levels; the perceived benefits of parentification served as a protective factor for the quality of the relationship with parents. Current findings extend the knowledge regarding the risk and protective factors of the siblings’ mental health when disability occurs in the family. Additionally, they inform family-based intervention programs, which should involve the whole family system for reducing distress and improving the wellbeing of siblings without disabilities

Parentification, distress, and relationship with parents as factors shaping the relationship between adult siblings and their brother/sister with disabilities

According to parentification theory, when the siblings of a brother/sister with disabilities assume parent-like duties, this role reversal is known as sibling-focused parentification. It has a significant impact on these siblings’ distress and the quality of their family relationships; 605 Italian adult siblings (19–26 years) of people with disabilities completed the online survey. Measures of siblings’ parentification, distress, quality of family relationships, social support, and perceived benefits of parentification were used. The hypothesized model aims to test, on the target sample, the distress and the quality of the relationship with parents as mediators on the interplay between the siblings’ parentification and their sibling relationship. Additionally, social support and perceived benefits of parentification as protective factors were considered. Results showed that the distress and the low quality of the relationship with parents negatively affected the interplay between the siblings’ parentification and the relationship with their own brother/sister with disabilities. Social support and the perceived benefits of parentification decreased the siblings’ distress levels; the perceived benefits of parentification served as a protective factor for the quality of the relationship with parents. Current findings extend the knowledge regarding the risk and protective factors of the siblings’ mental health when disability occurs in the family. Additionally, they inform family-based intervention programs, which should involve the whole family system for reducing distress and improving the wellbeing of siblings without disabilities

COVID-19 in an international European liver transplant recipient cohort.

Knowledge on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant recipients is lacking, particularly in terms of severity of the disease. The aim of this study was to describe the demographic, baseline clinical characteristics and early outcomes of a European cohort of liver transplant recipients with SARS-CoV-2 infection. We conducted an international prospective study across Europe on liver transplant recipients with SARS-CoV-2 infection confirmed by microbiological assay during the first outbreak of COVID-19 pandemic. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. 57 patients were included (70% male, median (IQR) age at diagnosis 65 (57-70) years). 21 (37%), 32 (56%) and 21 (37%) patients had one cardiovascular disease, arterial hypertension and diabetes mellitus, respectively. The most common symptoms were fever (79%), cough (55%), dyspnoea (46%), fatigue or myalgia (56%) and GI symptoms (33%). Immunosuppression was reduced in 22 recipients (37%) and discontinued in 4 (7%). With this regard, no impact on outcome was observed. Forty-one (72%) subjects were hospitalised and 11 (19%) developed acute respiratory distress syndrome. Overall, we estimated a case fatality rate of 12% (95% CI 5% to 24%), which increased to 17% (95% CI 7% to 32%) among hospitalised patients. Five out of the seven patients who died had a history of cancer. In this European multicentre prospective study of liver transplant recipients, COVID-19 was associated with an overall and in-hospital fatality rate of 12% (95% CI 5% to 24%) and 17% (95% CI 7% to 32%), respectively. A history of cancer was more frequent in patients with poorer outcome

Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis.

BACKGROUND: Kidney transplantation (KT) may restore fertility in CKD. The reasons why materno-foetal outcomes are still inferior to the overall population are only partially known. Comparison with the CKD population may offer some useful insights for management and counselling.Aim of this study was to analyse the outcomes of pregnancy after KT, compared with a large population of non-transplanted CKD patients and with low-risk control pregnancies, observed in Italy the new millennium. METHODS: We selected 121 live-born singletons after KT (Italian study group of kidney in pregnancy, national coverage about 75%), 610 live-born singletons in CKD and 1418 low-risk controls recruited in 2 large Italian Units, in the same period (2000-2014). The following outcomes were considered: maternal and foetal death; malformations; preterm delivery; small for gestational age baby (SGA); need for the neonatal intensive care unit (NICU); doubling of serum creatinine or increase in CKD stage. Data were analysed according to kidney diseases, renal function (staging according to CKD-EPI), hypertension, maternal age, partity, ethnicity. RESULTS: Materno-foetal outcomes are less favourable in CKD and KT as compared with the low-risk population. CKD stage and hypertension are important determinants of results. KT patients with e-GFR >90 have worse outcomes compared with CKD stage 1 patients; the differences level off when only CKD patients affected by glomerulonephritis or systemic diseases ('progressive CKD') are compared with KT. In the multivariate analysis, risk for preterm and early-preterm delivery was linked to CKD stage (2-5 versus 1: RR 3.42 and 3.78) and hypertension (RR 3.68 and 3.16) while no difference was associated with being a KT or a CKD patient. CONCLUSIONS: The materno-foetal outcomes in patients with kidney transplantation are comparable with those of nontransplanted CKD patients with similar levels of kidney function impairment and progressive and/or immunologic kidney diseas