Expanding the Grading of Recommendations Assessment, Development, and Evaluation (Ex-GRADE) for Evidence-Based Clinical Recommendations: Validation Study

Clinicians use general practice guidelines as a source of support for their intervention, but how much confidence should they place on these recommendations? How much confidence should patients place on these recommendations? Various instruments are available to assess the quality of evidence of research, such as the revised Wong scale (R-Wong) which examines the quality of research design, methodology and data analysis, and the revision of the assessment of multiple systematic reviews (R-AMSTAR), which examines the quality of systematic reviews

Molecular epigenetics, chromatin, and NeuroAIDS/HIV: Translational implications

We describe current research that applies epigenetics to a novel understanding of the immuno-neuropathogenesis of HIV-1 viral infection and NeuroAIDS. We propose the hypothesis that HIV-1 alters the structure-function relationship of chromatin, coding DNA and non-coding DNA, including RNA transcribed from these regions resulting in pathogenesis in AIDS, drug abuse, and NeuroAIDS. We discuss the general implications of molecular epigenetics with special emphasis on drug abuse, bar-codes, pyknons, and miRNAs for translational and clinical research. We discuss the application of the recent recursive algorithm of biology to this field and propose to synthesize the Genomic and Epigenomic views into a holistic approach of HoloGenomics

Molecular epigenetics, chromatin, and NeuroAIDS/HIV: Immunopathological implications

Epigenetics studies factors related to the organism and environment that modulate inheritance from generation to generation. Molecular epigenetics examines non-coding DNA (ncdDNA) vs. coding DNA (cdDNA), and pertains to every domain of physiology, including immune and brain function. Molecular cartography, including genomics, proteomics, and interactomics, seeks to recognize and to identify the multi-faceted and intricate array of interacting genes and gene products that characterize the function and specialization of each individual cell in the context of cell-cell interaction, tissue, and organ function. Molecular cartography, epigenetics, and chromatin assembly, repair and remodeling (CARR), which, together with the RNA interfering signaling complex (RISC), is responsible for much of the control and regulation of gene expression, intersect

Surface Roughness of Commercial Composites after Different Polishing Protocols: An Analysis with Atomic Force Microscopy

Polishing may increase the surface roughness of composites, with a possible effect on bacterial growth and material properties. This preliminary in vitro study evaluates the effect of three different polishing systems (PoGo polishers, Enhance, Venus Supra) on six direct resin composites (Gradia Direct, Venus, Venus Diamond, Enamel Plus HFO, Tetric Evoceram, Filtek Supreme XT)

Methadone, Buprenorphine, and Street Drug Interactions with Antiretroviral Medications

While street drugs appear unlikely to alter the metabolism of antiretroviral (ARV) medications, several ARVs may induce or inhibit metabolism of various street drugs. However, research on these interactions is limited. Case reports have documented life-threatening overdoses of ecstasy and gamma-hydroxybutyrate after starting ritonavir, an ARV that inhibits several metabolic enzymes. For opioid addiction, methadone or buprenorphine are the treatments of choice. Because a number of ARVs decrease or increase methadone levels, patients should be monitored for methadone withdrawal or toxicity when they start or stop ARVs. Most ARVs do not cause buprenorphine withdrawal or toxicity, even if they alter buprenorphine levels, with rare exceptions to date including atazanavir/ritonavir associated with significant increases in buprenorphine and adverse events related to sedation and mental status changes in some cases. There are newer medications yet to be studied with methadone or buprenorphine. Further, there are many frequently used medications in treatment of complications of HIV disease that have not been studied. There is need for continuing research to define these drug interactions and their clinical significance

The STRATOB study: design of a randomized controlled clinical trial of Cognitive Behavioral Therapy and Brief Strategic Therapy with telecare in patients with obesity and binge-eating disorder referred to residential nutritional rehabilitation

bstract BACKGROUND: Overweight and obesity are linked with binge eating disorder (BED). Effective interventions to significantly reduce weight, maintain weight loss and manage associated pathologies like BED are typically combined treatment options (dietetic, nutritional, physical, behavioral, cognitive-behavioral, pharmacological, surgical). Significant difficulties with regard to availability, costs, treatment adherence and long-term efficacy are present. Particularly Cognitive Behavioral Therapy (CBT) is the therapeutic approach indicated both in in-patient and in out-patient settings for BED. In recent years systemic and systemic-strategic psychotherapies have been implemented to treat patients with obesity and BED involved in familiar problems. Particularly a brief protocol for the systemic-strategic treatment of BED, using overall the strategic dialogue, has been recently developed. Moreover telemedicine, a new promising low cost method, has been used for obesity with BED in out-patient settings in order to avoid relapse after the in-patient step of treatment and to keep on a continuity of care with the involvement of the same clinical in-patient team. METHODS: The comparison between CBT and Brief Strategic Therapy (BST) will be assessed in a two-arm randomized controlled clinical trial. Due to the novelty of the application of BST in BED treatment (no other RCTs including BST have been carried out), a pilot study will be carried out before conducting a large scale randomized controlled clinical trial (RCT). Both CBT and BST group will follow an in-hospital treatment (diet, physical activity, dietitian counseling, 8 psychological sessions) plus 8 out-patient telephone-based sessions of psychological support and monitoring with the same in-patient psychotherapists. Primary outcome measure of the randomized trial will be the change in the Global Index of the Outcome Questionnaire (OQ-45.2). Secondary outcome measures will be the percentage of BED patients remitted considering the number of weekly binge episodes and the weight loss. Data will be collected at baseline, at discharge from the hospital (c.a. 1 month after) and after 6-12-24 months from the end of the in-hospital treatment. Data at follow-up time points will be collected through tele-sessions. DISCUSSION: The STRATOB (Systemic and STRATegic psychotherapy for OBesity), a comprehensive two-phase stepped down program enhanced by telepsychology for the medium-term treatment of obese people with BED seeking intervention for weight loss, will shed light about the comparison of the effectiveness of the BST with the gold standard CBT and about the continuity of care at home using a low-level of telecare (mobile phones). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0109625

Ebola: translational science considerations

We are currently in the midst of the most aggressive and fulminating outbreak of Ebola-related disease, commonly referred to as “Ebola”, ever recorded. In less than a year, the Ebola virus (EBOV, Zaire ebolavirus species) has infected over 10,000 people, indiscriminately of gender or age, with a fatality rate of about 50%. Whereas at its onset this Ebola outbreak was limited to three countries in West Africa (Guinea, where it was first reported in late March 2014, Liberia, where it has been most rampant in its capital city, Monrovia and other metropolitan cities, and Sierra Leone), cases were later reported in Nigeria, Mali and Senegal, as well as in Western Europe (i.e., Madrid, Spain) and the US (i.e., Dallas, Texas; New York City) by late October 2014. World and US health agencies declared that the current Ebola virus disease (EVD) outbreak has a strong likelihood of growing exponentially across the world before an effective vaccine, treatment or cure can be developed, tested, validated and distributed widely. In the meantime, the spread of the disease may rapidly evolve from an epidemics to a full-blown pandemic. The scientific and healthcare communities actively research and define an emerging kaleidoscope of knowledge about critical translational research parameters, including the virology of EBOV, the molecular biomarkers of the pathological manifestations of EVD, putative central nervous system involvement in EVD, and the cellular immune surveillance to EBOV, patient-centered anthropological and societal parameters of EVD, as well as translational effectiveness about novel putative patient-targeted vaccine and pharmaceutical interventions, which hold strong promise, if not hope, to curb this and future Ebola outbreaks. This work reviews and discusses the principal known facts about EBOV and EVD, and certain among the most interesting ongoing or future avenues of research in the field, including vaccination programs for the wild animal vectors of the virus and the disease from global translational science perspective

Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease

Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population