Biological and clinical abnormalities leading to cardiovascular disease during antiretroviral treatment in a university hospital in Abidjan

Antiretroviral drugs are involved in the occurrence of adverse effects. In Côte d'Ivoire, HIV1 treatment protocols are non-nucleoside reverse transcriptase inhibitors based. No study has been undertaken in the country about cardiovascular risk. Thus, the objective of our study was to assess the prevalence of biological abnormalities and clinical markers of cardiovascular risk during antiretroviral therapy. We conducted a prospective cross-sectional study with 238 patients who were on antiretroviral treatment including nonnucleoside reverse transcriptase inhibitors for at least 6 months in the Pneumophtisiology department of the university hospital of Cocody (Abidjan). Metabolic syndrome was determined according to NCEP-ATP III criteria. Biological parameters investigated were: triglyceride, HDL cholesterol and LDL, glucose and clinical parameters: blood pressure and waist circumference. Eleven patients (4.62%) have a metabolic syndrome, 17.6% had hypertriglyceridemia. An increase in LDL cholesterol and lower HDL-cholesterol were found in both cases in 13.9% of patients and an atherogenic index greater than 4.5 in 5% of patients. Hyperglycemia occurred during antiretroviral therapy in 28% of the study population. Patients who developed hypertension and increased waist circumference during antiretroviral therapy were 9.75% and 15.5% respectively. Our results testify to the potential existence of a cardiovascular risk during the non-nucleoside inhibitor used.© 2015 International Formulae Group. All rights reserved.Keywords: Antiretrovirals, biological, clinical abnormalities, cardiovascular risk

An Unusual Triad in Pediatric Neurology:A Case Report on Cerebral Palsy, Epilepsy, and Duchenne Muscular Dystrophy

We present a case of an unusual triad in pediatric neurology: a currently 12-year-old boy with cerebral palsy and epilepsy who was later also diagnosed with Duchenne muscular dystrophy. We describe the clinical path that resulted in this exceptional diagnosis. This case report illustrates how different neurological disorders may overshadow each other. In addition, it demonstrates that every child with cerebral palsy and either an atypical clinical course or with inexplicable laboratory values-as well as every infant boy born to a theoretical Duchenne muscular dystrophy carrier-should be subjected to additional investigations.</p

A Placebo‐Controlled Double‐Blinded Randomized Pilot Study of Combination Phytotherapy in Biochemically Recurrent Prostate Cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136500/1/pros23317_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136500/2/pros23317.pd

The In Situ Signature of Cyclotron Resonant Heating

The dissipation of magnetized turbulence is an important paradigm for describing heating and energy transfer in astrophysical environments such as the solar corona and wind; however, the specific collisionless processes behind dissipation and heating remain relatively unconstrained by measurements. Remote sensing observations have suggested the presence of strong temperature anisotropy in the solar corona consistent with cyclotron resonant heating. In the solar wind, in situ magnetic field measurements reveal the presence of cyclotron waves, while measured ion velocity distribution functions have hinted at the active presence of cyclotron resonance. Here, we present Parker Solar Probe observations that connect the presence of ion-cyclotron waves directly to signatures of resonant damping in observed proton-velocity distributions. We show that the observed cyclotron wave population coincides with both flattening in the phase space distribution predicted by resonant quasilinear diffusion and steepening in the turbulent spectra at the ion-cyclotron resonant scale. In measured velocity distribution functions where cyclotron resonant flattening is weaker, the distributions are nearly uniformly subject to ion-cyclotron wave damping rather than emission, indicating that the distributions can damp the observed wave population. These results are consistent with active cyclotron heating in the solar wind

Preimplantation genetic testing for more than one genetic condition:clinical and ethical considerations and dilemmas

STUDY QUESTION: Which clinical and ethical aspects of preimplantation genetic testing for monogenic disorders or structural rearrangements (PGT-M, PGT-SR) should be considered when accepting requests and counselling couples for PGT when applied for more than one condition (combination-PGT; cPGT-M/SR)? SUMMARY ANSWER: cPGT is a feasible extension of the practice of PGT-M/SR that may require adapting the criteria many countries have in place with regard to indications-setting for PGT-M/SR, while leading to complex choices that require timely counselling and information. WHAT IS KNOWN ALREADY: Although PGT-M/SR is usually performed to prevent transmission of one disorder, requests for PGTM/SR for more than one condition (cPGT-M/SR) are becoming less exceptional. However, knowledge about implications for a responsible application of such treatments is lacking. STUDY DESIGN, SIZE, DURATION: Retrospective review of all (40) PGT-M/SR applications concerning more than one genetic condition over the period 1995-2018 in the files of the Dutch national PGT centre. This comprises all relevant national data since the start of PGT in the Netherlands. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Data regarding cPGT-M/SR cases were collected by means of reviewing medical files of couples applying for cPGT-M/SR. Ethical challenges arising with cPGT-M/SR were explored against the background of PGT-M/SR regulations in several European countries, as well as of relevant ESHRE-guidance regarding both indications-setting and transfer-decisions. MAIN RESULTS AND THE ROLE OF CHANCE: We report 40 couples applying for cPGT-M/SR of which 16 couples started their IVF treatment. Together they underwent 39 IVF cycles leading to the birth of five healthy children. Of the couples applying for cPGT, 45% differentiated between a primary and secondary condition in terms of perceived severity. In the light of an altered balance of benefits and drawbacks, we argue the 'high risk of a serious condition' standard that many countries uphold as governing indications-setting, should be lowered for secondary conditions in couples who already have an indication for PGT-M/SR. As a consequence of cPGT, professionals will more often be confronted with requests for transferring embryos known to be affected with a condition that they were tested for. In line with ESHRE guidance, such transfers may well be acceptable, on the condition of avoiding a high risk of a child with a seriously diminished quality of life. LIMITATIONS, REASONS FOR CAUTION: We are the first to give an overview of cPGT-M/SR treatments. Retrospective analysis was performed using national data, possibly not reflecting current trends worldwide. WIDER IMPLICATIONS OF THE FINDINGS: Our observations have led to recommendations for cPGT-M/SR that may add to centre policy making and to the formulation of professional guidelines. Given that the introduction of generic methods for genomic analysis in PGT will regularly yield incidental findings leading to transfer requests with these same challenges, the importance of our discussion exceeds the present discussion of cPGT

Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms.</p> <p>Methods</p> <p>A <it>post hoc </it>analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects.</p> <p>Results</p> <p>Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS) scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, <it>low </it>anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm.</p> <p>Conclusion</p> <p>This study was a <it>post hoc </it>analysis of predictors of the placebo versus treatment response. Whilst this study does not explore neurobiological mechanisms, these observations are consistent with the hypotheses that 'drug' effects and placebo effects are not necessarily additive, and that mutually exclusive mechanisms may be operating in the two arms. The need for more research in the area of mechanisms and mediators of placebo versus active responses is supported.</p> <p>Trial Registration</p> <p>International Clinical Trials Registry ISRCTN98972974.</p

Major flaws in conflict prevention policies towards Africa : the conceptual deficits of international actors’ approaches and how to overcome them

Current thinking on African conflicts suffers from misinterpretations oversimplification, lack of focus, lack of conceptual clarity, state-centrism and lack of vision). The paper analyses a variety of the dominant explanations of major international actors and donors, showing how these frequently do not distinguish with sufficient clarity between the ‘root causes’ of a conflict, its aggravating factors and its triggers. Specifically, a correct assessment of conflict prolonging (or sustaining) factors is of vital importance in Africa’s lingering confrontations. Broader approaches (e.g. “structural stability”) offer a better analytical framework than familiar one-dimensional explanations. Moreover, for explaining and dealing with violent conflicts a shift of attention from the nation-state towards the local and sub-regional level is needed.Aktuelle Analysen afrikanischer Gewaltkonflikte sind häufig voller Fehlinterpretationen (Mangel an Differenzierung, Genauigkeit und konzeptioneller Klarheit, Staatszentriertheit, fehlende mittelfristige Zielvorstellungen). Breitere Ansätze (z. B. das Modell der Strukturellen Stabilität) könnten die Grundlage für bessere Analyseraster und Politiken sein als eindimensionale Erklärungen. häufig differenzieren Erklärungsansätze nicht mit ausreichender Klarheit zwischen Ursachen, verschärfenden und auslösenden Faktoren. Insbesondere die richtige Einordnung konfliktverlängernder Faktoren ist in den jahrzehntelangen gewaltsamen Auseinandersetzungen in Afrika von zentraler Bedeutung. Das Diskussionspapier stellt die große Variationsbreite dominanter Erklärungsmuster der wichtigsten internationalen Geber und Akteure gegenüber und fordert einen Perspektivenwechsel zum Einbezug der lokalen und der subregionalen Ebene für die Erklärung und Bearbeitung gewaltsamer Konflikte

Fiskalische Kosten einer steuerlichen Förderung von Forschung und Entwicklung in Deutschland - Eine empirische Analyse verschiedener Gestaltungsoptionen

Der Beitrag berechnet die Aufkommensausfälle verschiedener Gestaltungsmodelle für eine steuerliche Forschungsförderung in Deutschland auf Basis eines Mikrosimulationsmodells. Die fiskalischen Kosten betragen zwischen 464 Mio. € und 5.701 Mio. €. Eine Erstattungsoption der Steuergutschrift über die Gewerbe- und Körperschaftsteuerschuld hinaus ist unerlässlich, da sonst etwa ein Drittel der Unternehmen nicht oder nur teilweise in den Genuss der Förderung kommen würde und sich dadurch starke Verzerrungen zwischen ertragsstarken und ertragsschwachen Unternehmen ergeben. Eine Differenzierung der Fördersätze für KMU und große Unternehmen kann die Aufkommensausfälle wirksam begrenzen. Eine Kappungsgrenze in Höhe eines absoluten Betrages ist wegen der Verzerrungen innerhalb der Gruppe großer Unternehmen ungünstig. Als besonders pragmatisch erscheint eine Verrechnung der Steuergutschrift mit der abzuführenden Lohnsteuer

A Minimum of Three Motifs Is Essential for Optimal Binding of Pseudomurein Cell Wall-Binding Domain of Methanothermobacter thermautotrophicus

We have biochemically and functionally characterized the pseudomurein cell wall-binding (PMB) domain that is present at the C-terminus of the Surface (S)-layer protein MTH719 from Methanothermobacter thermautotrophicus. Chemical denaturation of the protein with guanidinium hydrochloride occurred at 3.8 M. A PMB-GFP fusion protein not only binds to intact pseudomurein of methanogenic archaea, but also to spheroplasts of lysozyme-treated bacterial cells. This binding is pH dependent. At least two of the three motifs that are present in the domain are necessary for binding. Limited proteolysis revealed a possible cleavage site in the spacing sequence between motifs 1 and 2 of the PMB domain, indicating that the motif region itself is protected from proteases