Acute rhabdomyolysis and delayed pericardial effusion in an Italian patient with Ebola virus disease : a case report

Background: During the 2013-2016 West Africa Ebola virus disease (EVD) epidemic, some EVD patients, mostly health care workers, were evacuated to Europe and the USA. Case presentation: In May 2015, a 37-year old male nurse contracted Ebola virus disease in Sierra Leone. After Ebola virus detection in plasma, he was medically-evacuated to Italy. At admission, rhabdomyolysis was clinically and laboratory-diagnosed and was treated with aggressive hydration, oral favipiravir and intravenous investigational monoclonal antibodies against Ebola virus. The recovery clinical phase was complicated by a febrile thrombocytopenic syndrome with pericardial effusion treated with corticosteroids for 10days and indomethacin for 2months. No evidence of recurrence is reported. Conclusions: A febrile thrombocytopenic syndrome with pericardial effusion during the recovery phase of EVD appears to be uncommon. Clinical improvement with corticosteroid treatment suggests that an immune-mediated mechanism contributed to the pericardial effusion

Molecular basis of USP7 inhibition by selective small-molecule inhibitors

Ubiquitination controls the stability of most cellular proteins, and its deregulation contributes to human diseases including cancer. Deubiquitinases remove ubiquitin from proteins, and their inhibition can induce the degradation of selected proteins, potentially including otherwise 'undruggable' targets. For example, the inhibition of ubiquitin-specific protease 7 (USP7) results in the degradation of the oncogenic E3 ligase MDM2, and leads to re-activation of the tumour suppressor p53 in various cancers. Here we report that two compounds, FT671 and FT827, inhibit USP7 with high affinity and specificity in vitro and within human cells. Co-crystal structures reveal that both compounds target a dynamic pocket near the catalytic centre of the auto-inhibited apo form of USP7, which differs from other USP deubiquitinases. Consistent with USP7 target engagement in cells, FT671 destabilizes USP7 substrates including MDM2, increases levels of p53, and results in the transcription of p53 target genes, induction of the tumour suppressor p21, and inhibition of tumour growth in mice

BRICS: Ecological and Sustainability Implications of their Growth

This paper examines the environmental implications of the growing BRICS economies (Brazil, Russia, India, China and South Africa). Exploring the thesis that these economies will be bigger than the largest developed economies by 2050. The BRICS nations encompass more than 25% of the world\u92s land area, home to over 40% of the world\u92s population and have a combined GDP of over $20 trillion. The future growth of these economies significantly impacts the rest of the world. This Paper focuses in the growth and consumption patters of the continuing industrialized nations the implications it can have for the Environment. Alternative development models are pitted against the current capitalistic models of development to see which is a more suitable pick for the future

Hypovitaminosis D in an Italian population of healthy subjects and hospitalized patients

The present study aimed to investigate the prevalence and seasonal variation of hypovitaminosis D (defined as serum 25-hydroxyvitamin D level below 30 nmol/l) among healthy subjects and hospitalized patients living in central Italy. We studied 297 subjects, 131 in February 1997 and 166 in July 1997, subdivided into four groups: (a) young healthy blood donors; (b) healthy postmenopausal women; (c) inpatients with various medical diseases and (d) inpatients engaged in long-term rehabilitation programmes because of various neurological disorders. In all subjects and patients serum levels of 25-hydroxyvitamin D were measured by radioimmunoassay. We found a significant seasonal variation (P < 0.0001) of serum 25-hydroxyvitamin D levels, mean values being higher in summer in all groups, except in patients with a longer hospitalization time (group (d)). In each group, a significantly higher prevalence of hypovitaminosis D was found in winter compared with summer time (P < 0.001), being unexpectedly high in postmenopausal women (winter 32% and summer 4.5%); furthermore, in both seasons, inpatients were characterized by the highest incidences of hypovitaminosis, particularly those in group (d) (winter 82.3% and summer 57.8%). The results of the present study emphasize the importance of 25-hydroxyvitamin D measurement, and the need to increase vitamin D intake in Italy; foodstuff fortification and supplement use must be considered in order to prevent negative effects of vitamin D deficiency on skeletal integrity

A cluster-randomized trial of a brief multi-component intervention to improve tobacco outcomes in substance use treatment.

BackgroundSmoking prevalence is high among people in substance use disorder (SUD) treatment, and program interventions to address smoking are often complex and lengthy. This cluster-randomized trial tested whether a brief multi-component intervention impacted tobacco outcomes among staff and clients.MethodsSeven SUD treatment programs were randomly assigned to the multi-component intervention or to waitlist control. The 6-month intervention included a leadership motivation assessment, program incentives, 4 staff training sessions and a leadership learning community session. Survey data were collected from staff and clients at pre- and post-intervention. Outcomes were first compared across condition (intervention vs waitlist control), and then examined pre- to post-intervention with condition collapsed.ResultsStaff in the intervention (n = 48) and control conditions (n = 26) did not differ at post-intervention on smoking prevalence, self-efficacy to help clients quit, or practices used to help clients quit smoking. Intervention clients (n = 113) did not differ from controls (n = 61) in smoking prevalence or receipt of tobacco services. Pre-post comparisons collapsed across condition showed a decrease in client and staff smoking prevalence, which could not be attributed to the intervention, and a decrease in client receipt of cessation medication.ConclusionThe brief multi-component intervention did not support changes in smoking prevalence or in tobacco-related services received by clients. Other intervention features are needed to reduce smoking among SUD clients.Trial registrationRandomization occurred at the program level and outcomes measured are program-level measures. Accordingly, the trial is not registered

Pre-implementation Assessment of Tobacco Cessation Interventions in Substance Use Disorder Residential Programs in California

BackgroundAcross the United States, substance use disorder (SUD) treatment programs vary in terms of tobacco-related policies and cessation services offered. Implementation of tobacco-related policies within this setting can face several barriers. Little is known about how program leadership anticipate such barriers at the pre-implementation phase. This study used the Consolidated Framework for Implementation Research (CFIR) during the pre-implementation stage to identify factors that may influence the implementation stage of tobacco-related cessation policies and services in residential SUD programs.MethodsWe conducted semi-structured qualitative interviews with sixteen residential treatment program directors in California. The analysis was guided by a deductive approach using CFIR domains and constructs to develop codes and identify themes. ATLAS.ti software was used to facilitate thematic analysis of interview transcripts.FindingsThemes that arose as anticipated facilitators for implementation included the relative advantage of the intervention vs. current practice, external policies/incentives to support tobacco-related policy, program directors' strong commitment and high self-efficacy to incorporate cessation into SUD treatment, and recognizing the importance of planning and engaging opinion leaders. Potential barriers included the SUD recovery culture, low stakeholder engagement, organizational culture, lack of workforce expertise, and lack of reimbursement for smoking cessation services.ConclusionTo support successful implementation of tobacco-related organizational change interventions, staff and clients of residential SUD programs require extensive education about the effectiveness of evidence-based medications and behavioral therapies for treating tobacco dependence. Publicly funded SUD treatment programs should receive support to address tobacco dependence among their clients through expanded reimbursement for tobacco cessation services