An evaluation of osteopathic treatment on psychological outcomes with patients suffering from chronic pain: A prospective observational cohort study collected through a health and well-being academy

Co-morbid mental health conditions such as anxiety, depression and fear avoidance are often associated with chronic pain. This novel study aimed to explore the impact of osteopathic treatment on several psychological outcome measures relating to anxiety, depression, mental health and fear avoidance for a chronic pain population receiving osteopathic treatment over a 2-week period. The findings show that there were significant reductions in anxiety, pain, mental health dysfunction and improvements in self-care. These results are promising, and it is suggested that now a full-scale randomised controlled trial should be conducted

Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid

BACKGROUND: Increased prevalences of diabetes mellitus have been reported among individuals chronically exposed to inorganic arsenic (iAs). However, the mechanisms underlying the diabetogenic effects of iAs have not been characterized. We have previously shown that trivalent metabolites of iAs, arsenite (iAs(III)) and methylarsonous acid (MAs(III)) inhibit insulin-stimulated glucose uptake (ISGU) in 3T3-L1 adipocytes by suppressing the insulin-dependent phosphorylation of protein kinase B (PKB/Akt). OBJECTIVES: Our goal was to identify the molecular mechanisms responsible for the suppression of PKB/Akt phosphorylation by iAs(III) and MAs(III). METHODS: The effects of iAs(III) and MAs(III) on components of the insulin-activated signal transduction pathway that regulate PKB/Akt phosphorylation were examined in 3T3-L1 adipocytes. RESULTS: Subtoxic concentrations of iAs(III) or MAs(III) had little or no effect on the activity of phosphatidylinositol 3-kinase (PI-3K), which synthesizes phosphatidylinositol-3,4,5-triphosphate (PIP(3)), or on phosphorylation of PTEN (phosphatase and tensin homolog deleted on chromosome ten), a PIP(3) phosphatase. Neither iAs(III) nor MAs(III) interfered with the phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK-1) located downstream from PI-3K. However, PDK-1 activity was inhibited by both iAs(III) and MAs(III). Consistent with these findings, PDK-1-catalyzed phosphorylation of PKB/Akt(Thr308) and PKB/Akt activity were suppressed in exposed cells. In addition, PKB/Akt(Ser473) phosphorylation, which is catalyzed by a putative PDK-2, was also suppressed. Notably, expression of constitutively active PKB/Akt restored the normal ISGU pattern in adipocytes treated with either iAs(III) or MAs(III). CONCLUSIONS: These results suggest that inhibition of the PDK-1/PKB/Akt-mediated transduction step is the key mechanism for the inhibition of ISGU in adipocytes exposed to iAs(III) or MAs(III), and possibly for impaired glucose tolerance associated with human exposures to iAs

The April 16 2016 Mw7.8 Muisne Earthquake in Ecuador – Preliminary Observations from the EEFIT Reconnaissance Mission of May 24 - June 7

On April 16 2016 an Mw7.8 earthquake with epicentre 29km south-southeast of Muisne in northern Manabí caused around 700 fatalities, injured 30,000 and destroyed several sections of the towns of Pedernales, Portoviejo, Canoa, Bahía de Caráquez and Manta, most of them important centres of tourism on the coast of Ecuador. During May 24-June 7 a team was deployed by the Earthquake Engineering Field Investigation Team (EEFIT) with the objective of surveying the damage and recording observations that would help the scientific and professional community understand the event and its consequences. The team, all co-authors of this paper, investigated structural damage patterns, surveyed 1,332 buildings, validated landslide data obtained from satellite imagery for 30 sites, and interviewed 120 families at 3 shelters. The damage observed in low- and mid-rise buildings seems to correlate well with the spectral response measured in Manta, Portoviejo, and Pedernales. Satellite-based landslide identification proved effective in an 80-90% of the cases investigated. The immediate unemployment spike, based on our limited survey, seemed to reach about 50% in the affected population

Opportunities for improved cardiovascular disease prevention in oncology patients

PURPOSE OF REVIEW: Cancer patients often have cardiovascular risk factors at the time of cancer diagnosis, which are known to increase the risk of cardiotoxicity. Cancer survivors have significantly higher cardiovascular risk. Current cardiovascular disease prevention guidelines are based on studies that largely excluded these patients. We reviewed recent data regarding cardiovascular disease prevention in this population. RECENT FINDINGS: Nonpharmacologic therapies aiming to reduce 'lifestyle toxicity' produced by cancer treatments have demonstrated potential to decrease the incidence of adverse outcomes. Exercise before, during and after cancer treatment not only promotes higher quality of life and cardiorespiratory fitness but also reduces adverse cardiovascular outcomes. Lipid and cardiometabolic disease management is paramount but predominantly based on data that excludes these populations of cancer patients and survivors. SUMMARY: A comprehensive approach including medical evaluation, prescriptive exercise, cardiac risk factor modification, education, counseling, pharmacologic and behavioral interventions are needed in cancer patients. These interventions constitute the core of cardio-oncology rehabilitation programs, which if implemented appropriately may help reduce cardiovascular events in this population. Knowledge gaps in these areas are starting to be addressed by ongoing clinical trials

Native American Children and Their Reports of Hope: Construct Validation of the Children's Hope Scale

Child reports of hope continue to be utilized as predictors of positive adjustment; however, the utilization of the hope construct has not been assessed within the culturally diverse Native American child group. The present study investigated the applicability of the Hope theory among 96 Native American children in the Midwest. Measures included the Children’s Hope Scale and a Hope Interview. Native American children in the current sample appear to conceptualize hope as a way to reach goals as did the children in the normative sample. Results from the factor analysis demonstrate that the factor structure found in the current study was similar to the factor structure found in the standardization sample. Because of the similar Hope theory conceptualization and factor structure, interventions focused on the positive psychology construct of hope may be applicable within a Native American child population

Uncultivated Microbial Eukaryotic Diversity: A Method to Link ssu rRNA Gene Sequences with Morphology

Protists have traditionally been identified by cultivation and classified taxonomically based on their cellular morphologies and behavior. In the past decade, however, many novel protist taxa have been identified using cultivation independent ssu rRNA sequence surveys. New rRNA “phylotypes” from uncultivated eukaryotes have no connection to the wealth of prior morphological descriptions of protists. To link phylogenetically informative sequences with taxonomically informative morphological descriptions, we demonstrate several methods for combining whole cell rRNA-targeted fluorescent in situ hybridization (FISH) with cytoskeletal or organellar immunostaining. Either eukaryote or ciliate-specific ssu rRNA probes were combined with an anti-α-tubulin antibody or phalloidin, a common actin stain, to define cytoskeletal features of uncultivated protists in several environmental samples. The eukaryote ssu rRNA probe was also combined with Mitotracker® or a hydrogenosomal-specific anti-Hsp70 antibody to localize mitochondria and hydrogenosomes, respectively, in uncultivated protists from different environments. Using rRNA probes in combination with immunostaining, we linked ssu rRNA phylotypes with microtubule structure to describe flagellate and ciliate morphology in three diverse environments, and linked Naegleria spp. to their amoeboid morphology using actin staining in hay infusion samples. We also linked uncultivated ciliates to morphologically similar Colpoda-like ciliates using tubulin immunostaining with a ciliate-specific rRNA probe. Combining rRNA-targeted FISH with cytoskeletal immunostaining or stains targeting specific organelles provides a fast, efficient, high throughput method for linking genetic sequences with morphological features in uncultivated protists. When linked to phylotype, morphological descriptions of protists can both complement and vet the increasing number of sequences from uncultivated protists, including those of novel lineages, identified in diverse environments

Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania.

To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians

The Role of Innate APOBEC3G and Adaptive AID Immune Responses in HLA-HIV/SIV Immunized SHIV Infected Macaques

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

SMART Research: Toward Interdisciplinary River Science in Europe

Interdisciplinary science is rapidly advancing to address complex human-environment interactions. River science aims to provide the methods and knowledge required to sustainably manage some of the planet’s most important and vulnerable ecosystems; and there is a clear need for river managers and scientists to be trained within an interdisciplinary approach. However, despite the science community’s recognition of the importance of interdisciplinary training, there are few studies examining interdisciplinary graduate programs, especially in science and engineering. Here we assess and reflect on the contribution of a 9-year European doctoral program in river science: ‘Science for MAnagement of Rivers and their Tidal Systems’ Erasmus Mundus Joint Doctorate (SMART EMJD). The program trained a new generation of 36 early career scientists under the supervision of 34 international experts from different disciplinary and interdisciplinary research fields focusing on river systems, aiming to transcend the boundaries between disciplines and between science and management. We analyzed the three core facets of the SMART program, namely: (1) interdisciplinarity, (2) internationalism, and (3) management-oriented science. We reviewed the contents of doctoral theses and publications and synthesized the outcomes of two questionnaire surveys conducted with doctoral candidates and supervisors. A high percentage of the scientific outputs (80%) were interdisciplinary. There was evidence of active collaboration between different teams of doctoral candidates and supervisors, in terms of joint publications (5 papers out of the 69 analyzed) but this was understandably quite limited given the other demands of the program. We found evidence to contradict the perception that interdisciplinarity is a barrier to career success as employment rates were high (97%) and achieved very soon after the defense, both in academia (50%) and the private/public sector (50%) with a strong international dimension. Despite management-oriented research being a limited (9%) portion of the ensemble of theses, employment in management was higher (22%). The SMART program also increased the network of international collaborations for doctoral candidates and supervisors. Reflections on doctoral training programs like SMART contribute to debates around research training and the career opportunities of interdisciplinary scientists