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Introduction Tetraplegia causes extensive sensorimotor deficits affecting activity, participation and quality of life. People with C6-C7 tetraplegia can learn to grasp objects by performing wrist extension movement (ie, tenodesis grasp), and motor imagery (MI) added to rehabilitation significantly improved tenodesis grasp. We hypothesise that this improvement can be further boosted by adding neurofeedback during MI. Thus, we design a randomised controlled trial investigating the effect of MI training on grasping ability in people with C6-C7 tetraplegia.Methods and analysis We will perform a bicentric, assessor-blinded, randomised controlled study. During rehabilitation, 21 inpatients with C6-C7 tetraplegia will be allocated to MI with neurofeedback (MI training with graphical display on a computer screen based on mu (8–13 Hz) and beta (18–25 Hz) frequency rhythms measured with 32-channel electroencephalography), MI alone (only MI training) and control (watching movies and visualisation of geometric shapes). All participants will receive three 45-min training sessions per week for 5 weeks.The primary outcome measure will be wrist extension angle immediately after the intervention during tenodesis grasp measured with a 3D motion analysis system (VICON). Secondary outcomes will include a range of measures: kinematic, grip strength, upper limb range of motion, upper limb strength (manual muscle test and hand-held dynamometer measure), dexterity (box and block test, 9-hole peg test, Jebsen test, capabilities of upper extremity questionnaire), quality of life (WHOQOL-Bref), daily life autonomy (Quadriplegic Index of Function), MI capacity and brain reorganisation (magnetoencephalography only available in Lyon, n=15). We will measure all outcomes five times: during weeks 1, 3 and 5 (baseline), week 11 (immediately after the intervention end) and week 18 (8 weeks after the intervention end).Ethics and dissemination Ethical approval was granted on 29 September 2017 (CPP Nord-Ouest-IV 17/25, N°2017-A00990-53). Dissemination will occur via presentation of results in scientific meetings and publication in peer-reviewed academic journals.Trial registration number NCT03190863 (ClinicalTrials.gov).

Abstract In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen. Chlorantraniliprole (CHL) is an insecticide of the anthranilic diamide class which main mode of action is to alter the function of intracellular Ca2+ release channels (known as RyRs, for ryanodine receptors). In the honey bee, it was recently found to be more toxic when applied on the dorsal part of the abdomen, suggesting a direct cardiotoxicity. In the present study, a short-term exposure of semi-isolated bee hearts to CHL (0.1–10 µM) induces alterations of cardiac contraction. These alterations range from a slow-down of systole and diastole kinetics, to bradycardia and cardiac arrest. The bees heart wall is made of a single layer of semi-circular cardiomyocytes arranged concentrically all along the long axis of tube lumen. Since the heart tube is suspended to the cuticle through long tubular muscles fibers (so-called alary muscle cells), the CHL effects in ex-vivo heart preparations could result from the modulation of RyRs present in these skeletal muscle fibers as well as cardiomyocytes RyRs themselves. In order to specifically assess effects of CHL on cardiomyocytes, for the first time, intact heart cells were enzymatically dissociated from bees. Exposure of cardiomyocytes to CHL induces an increase in cytoplasmic calcium, cell contraction at the highest concentrations and depletion of intracellular stores. Electrophysiological properties of isolated cardiomyocytes were described, with a focus on voltage-gated Ca2+ channels responsible for the cardiac action potentials depolarization phase. Two types of Ca2+ currents were measured under voltage-clamp. Exposure to CHL was accompanied by a decrease in voltage-activated Ca2+ currents densities. Altogether, these results show that chlorantraniliprole can cause cardiac defects in honey bees.

Background Barth syndrome is a rare, life-threatening X-linked recessive mitochondrial disorder of lipid metabolism primarily affecting males. Previous research suggests that bezafibrate may ameliorate cellular lipid abnormalities and reduce cardiac dysfunction in an animal model. Objectives Estimate the effect of bezafibrate on clinical, biochemical, and quality-of-life outcomes. Investigate whether within-participant clinical changes parallel in vitro changes in cardiolipin ratio/profile and mitochondrial morphology when each participant’s cells are cultured with bezafibrate. Investigate as for objective 2, culturing each participant’s cells with resveratrol. Describe the most feasible methods and standardised outcome measures to optimise the conduct of future trials and evaluations in Barth syndrome. Describe features of the research infrastructure which optimised recruitment, retention and communication with families and people with Barth syndrome. Describe the perceptions of participants and their families about the research and any important potential barriers to participation. Design Randomised, placebo-controlled, crossover trial of bezafibrate versus placebo. Setting NHS hospital providing UK-wide Barth Syndrome Service. Participants Males aged ≥ 6 years with a confirmed diagnosis of Barth syndrome with stable cardiac status, able to swallow tablets of bezafibrate/placebo. Exclusions were: hypersensitivity or allergy to bezafibrate or any component of bezafibrate; hepatic, liver or renal dysfunction; gallbladder disease; or recent deterioration in general health. Interventions Fifteen weeks of bezafibrate in one period and placebo in a second period, or vice versa (randomly allocated), with at least a 1-month washout between periods. Main outcome measures The primary outcome was peak VO2; secondary outcomes were cardiac function rest and exercise echocardiography and magnetic resonance imaging, cardiolipin ratio, quality of life, dynamic skeletal muscle P-magnetic resonance spectroscopy, mitochondrial studies and neutrophil counts, and adverse events. Outcomes were measured at baseline and the end of each period. Results Eleven males were studied; all attended all three assessments. There was no difference in peak VO2 between periods (0.66 ml/kg/min lower with bezafibrate than placebo, 95% confidence interval 2.34 to 1.03; p = 0.43). There was a trend towards a higher left ventricular ejection fraction with bezafibrate when measured by echocardiography but not magnetic resonance imaging, and better echocardiography-derived rest longitudinal and circumferential strain with bezafibrate. There was no difference in quality of life or cardiolipin ratio between periods. Skeletal muscle 31P magnetic resonance spectroscopy was performed cross-sectionally and showed a trend to higher Tau and lower Qmax indices in the bazafibrate group. Two participants had serious, expected adverse reactions when taking bezafibrate; otherwise, bezafibrate was well tolerated. Limitations The sample size was very small; the bezafibrate dose may have been too low or 15 weeks too short to observe an effect; measurements of mitochondrial content and membrane potential were highly variable; P-magnetic resonance spectroscopy was available only at the final assessment. Conclusions This study did not show significant improvement in the primary and secondary outcomes with bezafibrate treatment. Future work Elamipretide, studied in a small crossover trial in the USA, is another potential intervention which may be worth evaluating in an international study. Trial registration This trial is registered as ISRCTN58006579. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/205/56) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 13. See the NIHR Funding and Awards website for further award information. Plain language summary Barth syndrome is a rare genetic syndrome with mutations in the tafazzin gene causing long-term effects in several organ systems, leading to significant lifelong comorbidities and a reduced quality of life. Barth syndrome shows an X-linked inheritance, hence it is almost exclusively present in males. Tafazzin gene mutations impair overall cell energy metabolism, and affected individuals show compromise of the immune system with a high risk for life-threatening infections, as well as cardiac dysfunction and cardiomyopathy, muscle and general fatigue, and generally reduced mobility also leading to psychological challenges and dysfunction. Currently, specific medical therapies are limited to symptomatic treatment, and drug therapies targeting the causative mitochondrial energy disturbance are urgently needed. This randomised controlled trial explored the use of oral bezafibrate, a licensed drug that can improve cell energy metabolism. Eleven male patients received either bezafibrate or a placebo for 4 months. Exercise capacity by cardiopulmonary exercise testing on a cycle ergometer, as the primary outcome measurement, as well as cardiac function by echocardiography and magnetic resonance imaging, and cellular anatomy and function by in vitro assays and microscopy, were measured before and after this 4-month period. Bezafibrate did not significantly improve exercise capacity, cardiac function or the cellular metabolism, although several cardiac function parameters showed slight improvements with bezafibrate treatment. No significant adverse effects were recorded. The limitations of the trial were its low participant number and the relatively short duration of the drug treatment phase. The trial did prove that complex randomised controlled drug trials are feasible in people with rare diseases. Adherence was good, with parents reporting few difficulties with pill swallowing. The qualitative interviews also found that the study was acceptable to participants and the burden of participating not too onerous. We hope the research can provide a template for future studies. Scientific summary Introduction Barth syndrome is a very rare, life-threatening, X-linked recessive genetic disease almost exclusively affecting young males, caused by abnormal lipids in mitochondria. The tafazzin gene (TAZ) encodes tafazzin, a phospholipid acyltransferase. Tafazzin transfers unsaturated fatty acids with acyl chains from phospholipids to monolysocardiolipin (MLCL) and regulates remodelling and maturation of cardiolipin, a phospholipid located exclusively in the inner mitochondrial membrane. Mature tetralinoleoyl-cardiolipin (L4-CL) is essential in the mitochondrial membrane for maintaining mitochondrial membrane potential, structural integrity of electron transport chain complexes and mitochondrial cristae architecture. Cardiolipin is a major constituent of inner mitochondrial membranes, and the major effects of the aberrant gene are on muscular tissues. Cardiac and skeletal manifestations of Barth syndrome are thought to result from impaired formation of respiratory chain super-complexes. TAZ mutations decrease L4-CL and increase intermediate species of MLCL, resulting in a marked increase in the MLCL : L4-CL ratio, which provides a highly sensitive and specific biochemical test for Barth syndrome. Barth syndrome is characterised by many gene mutations and profound phenotypic variability between affected patients within families and those in different families. The disease carries many risks and problems for its sufferers, as well as major healthcare costs. Almost one-third (30%) of living UK patients have undergone cardiac transplantation. Several patients who have died due to cardiac rejection or post-transplant lymphoproliferative disease had previously undergone cardiac transplantation. Other patients who have died deteriorated too fast to undergo transplantation or died of complications while awaiting transplantation. Neutropenia is another life-threatening issue. Two-thirds of UK patients are treated with granulocyte colony-stimulating factor by subcutaneous injection. Managing neutropenia in this disease is challenging, since patients have highly variable neutrophil counts, which prevents administration of a consistent daily dose and requires repeated blood counts and physician oversight. Exercise intolerance, lethargy and fatigue are universal, interfering with daily life, schoolwork and play and often necessitating use of a wheelchair. Patients cannot perform strenuous or demanding jobs. Many have major feeding problems from infancy through to adult life; for example, requiring feeding via gastrostomies. There can be rapid deterioration during periods of stable health despite expert medical care. Ventricular arrhythmia (tachycardia or fibrillation) affects 10% of adolescents and can cause sudden cardiac death at any time. There are no specific treatments for Barth syndrome. There is no evidence that standard medications for cardiomyopathy ameliorate long-term poor outcomes. Treatment is multidisciplinary and currently limited to treating intercurrent bacterial infections, bone marrow support, physiotherapy, nutritional support, management of heart failure and arrhythmia, and consideration for heart transplantation. Experiments using lymphoblasts from patients with Barth syndrome show that either bezafibrate or resveratrol can partially normalise the deranged cardiolipin ratio. This may be important, since some patients with Barth syndrome who lack neutropenia and tend to have good exercise tolerance have cardiolipin ratios intermediate between those of typical patients and normal individuals. Bezafibrate also improved left ventricular function and showed other benefits at supraphysiological doses in a TAZ knockdown mouse model. This trial was motivated by the need for disease-specific therapy to prevent morbidity, mortality, psychological distress, and disruption of quality of life (QoL) in affected patients and their families. An effective therapy also has the potential to generate savings for the NHS. Bezafibrate is a lipid-lowering drug used in adults and children, with a good safety record in long-term use. These characteristics made it a candidate for investigation. Bezafibrate has been reported to significantly ameliorate a mitochondrial myopathy in adults and shown promising results in several animal/human cellular models of mitochondrial disease. Several of the laboratory assays and clinical investigations proposed in this study were also considered potentially important beyond the scope of this specific study, to assess associations between genotype and phenotype and for future evaluations of therapies in Barth syndrome. Objectives Estimate the effect on clinical, biochemical and QoL outcome measures of bezafibrate compared to placebo. Investigate whether clinical improvements parallel in vitro changes in cardiolipin ratio and mitochondrial morphology in each participant’s cells when cultured with bezafibrate. Investigate whether clinical improvements and culture findings with bezafibrate parallel in vitro changes in each participant’s cells when exposed to resveratrol in laboratory culture. Describe the most feasible methods and standardised outcome measures for future trials. Describe features of the research infrastructure which optimised recruitment, retention and communication with participants and families. Describe participants’ and their families’ perceptions of research and important potential barriers to participation. Methods Study design and participants CARDIOlipin MANipulation trial (CARDIOMAN) was a double-blind, placebo-controlled crossover randomised trial. Treatment was given in two 15-week periods with a minimum of 1 month’s washout period between these when no treatment was given. Twenty-six males and one female with the disease were alive in the UK when the trial was designed. Males aged ≥ 6 years in the UK diagnosed with Barth syndrome were eligible. Exclusion criteria were: hypersensitivity to bezafibrate or component of the investigational medicinal product (IMP), photoallergic or phototoxic reaction to fibrate, unstable cardiac condition, cardiac chamber shortening fraction < 25% or significant decrease in shortening fraction in the preceding year, atrial or ventricular arrhythmia not stabilised by treatment, inability to swallow the IMP, hepatic dysfunction, renal impairment (creatinine clearance < 90 ml/min), gallbladder disease, recent unspecified significant deterioration in general health, prisoners and adults lacking capacity to provide informed consent. Randomisation and masking Participants were randomised to receive either bezafibrate then placebo, or the reverse order. Allocations were generated in advance by the Bristol Trials Centre and provided to the trial pharmacy which dispensed the IMP. All investigators, members of the research team (apart from pharmacy) and participants remained blind to treatment allocation. Intervention and procedures The intervention IMP was bezafibrate taken orally as 100-mg tablets. Children aged 6–9 years started on 100 mg once daily for the first 4 weeks and, if well tolerated, increased to 100 mg twice daily for the remaining 11 weeks. Children aged 10–17 years started on 200 mg once daily for the first 4 weeks and, if well tolerated, increased to 200 mg twice daily for the remaining 11 weeks. Adults (≥ 18 years) took 200 mg twice daily throughout. The comparator IMP was placebo taken orally as visually identical tablets and manufactured to be as similar as possible in taste and smell to the intervention. The IMP was prescribed at the start of the first period and again at the end of the first period for the second period. Outcomes All in vivo outcomes except magnetic resonance spectroscopy (MRS) were assessed three times: at baseline and in the final week of each treatment phase. The primary outcome measure was peak oxygen consumption on bicycle ergometry [peak volume of oxygen (VO2)]. Secondary outcomes were: MLCL/L4-CL ratio and cardiolipin profile in blood cells; phosphocreatine (PCr)/adenosine 5’ triphosphate (ATP) ratio in cardiac muscle on 31P MRS; skeletal muscle oxidative function/on 31P MRS; QoL [age-appropriate Pediatric Quality of Life Inventory (PedsQLTM) questionnaires]; absolute neutrophil count; amino acid expression (serum arginine and cysteine); cardiac function [left and right ventricular function: left ventricular ejection fraction (LVEF%), right ventricular ejection fraction (RVEF%); and 2-D longitudinal and circumferential strain at rest, peak exercise and after recovery]; mitochondrial size and number in lymphocytes; mitochondrial area in lymphocytes and as a proportion of cytoplasm area; mitochondrial function and cristae organisation in lymphocytes/neutrophils; arrhythmia profile from 12-lead electrocardiogram at rest and during exercise. Qualitative research methods explored participants’ and families’ experiences of the different interventions. Adverse events Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from participants from the time of consent until 1 month after the final period. Participants’ general practitioners were asked to inform the research team of suspected AEs. Participants were asked questions about SAEs/AEs at each research clinic visit and in monthly phone calls, including during the washout period. SAEs were reviewed by the Chief Investigator, who decided whether the SAE was related to bezafibrate. Statistical analysis A total of 20 males aged ≥ 6 years were potentially eligible. The sample size was dictated by the number of eligible boys willing to take part. The primary analysis estimated the difference in mean peak VO2 between placebo and bezafibrate periods (two-tailed 5% significance level). A sample size of 12 participants allowed the trial to detect a difference of 0.90 (within subject) standard deviations with 80% power. The statistical analysis plan (SAP) prespecified that all analyses should be conducted according to the intention-to-treat (ITT) principle. The ITT population comprised all participants and periods, according to the randomised allocations. The safety population comprised all randomised participants, according to the treatment received in each period, who received at least one dose of IMP. All statistical tests were two-sided and used a 5% significance level, except for interactions that used a 10% significance level. Treatment effects were estimated with 95% confidence intervals (CIs). No formal adjustment was made for multiple testing. The treatment effect for the primary outcome was analysed using mixed linear regression models, adjusting for period (fixed effect; exploring interactions where necessary) and participants (random effects). Model assumptions were tested using standard methods, and the carry-over effect was estimated by including treatment order. Treatment effects for continuously scaled secondary outcomes (prespecified in the SAP) were estimated and tested using the same methods. Results There was no statistically significant difference between bezafibrate and placebo in peak VO2, which was 0.66 ml/kg/min lower (95% CI −2.34 to 1.03; p = 0.43) with bezafibrate. There was a borderline statistically significant increase in LVEF% using echocardiography (3.72%, 95% CI −0.26% to 7.69%; p = 0.065) but no evidence of a difference when using magnetic resonance imaging (MRI) (0.15%, 95% CI −3.21% to 3.51%; p = 0.926). There was also no difference for RVEF% between bezafibrate and placebo (0.32, 95% CI −2.32 to 2.96; p = 0.801). Longitudinal and circumferential strain at rest were better (lower) with bezafibrate than with placebo; differences were –1.67 (95% CI −3.11 to −0.22; p = 0.026) and −2.72 (95% CI −5.03 to −0.40; p = 0.024) respectively. There was no difference in diastolic ratio at rest between bezafibrate and placebo, and no differences in strain or diastolic ratio at peak exercise or after 2 minutes’ recovery. All participants had sinus rhythm at rest and during exercise for all three time points. Magnetic resonance spectroscopy was only performed after the second period for 10 participants. PCr/ATP ratio in cardiac muscle was not collected. Cross-sectionally (five vs. five participants), MRS appeared to increase Tau and reduce Qmax parameters with bezafibrate compared to placebo. Monolysocardiolipin/L4-CL ratio did not differ between bezafibrate and placebo but deteriorated in the second period (20% higher, 95% CI 3% to 40%; p = 0.024). Neutrophil count also showed no difference between bezafibrate and placebo but increased in the second period (2.26, 95% CI 0.08 to 4.45; p = 0.043). Plasma cysteine increased with bezafibrate (32% higher, 95% CI 8% to 62%; p = 0.001) but plasma arginine did not (25% higher, 95% CI −10% to 72%; p = 0.180). Mitochondrial outcomes on blood samples did not show marked differences and were not formally compared. Quality-of-life scores were transformed to a 0–100 scale (higher being better). Bezafibrate had no effect on core (−3.41, 95% CI −8.67 to 1.86; p = 0.192) or fatigue (1.71, 95% CI −6.28 to 9.71; p = 0.659) QoL scores. Emerging themes identified in qualitative interviews were classified as overarching, related to lived experience with Barth syndrome, and trial participation and conduct. Participants and families were pleased to take part in the trial, viewing participation as ‘giving back’ to the medical community. No participant withdrew, and the trial was not perceived to be too onerous for families. Participating in the research gave both individuals and families a sense of responsibility for their condition, partly driven by appreciation for the Barth Syndrome Service and staff expertise. Monolysocardiolipin/L4-CL ratio in vitro was estimated from samples of cells incubated with control, bezafibrate or resveratrol. Each drug reduced the MLCL/L4-CL ratio, largely by increasing intermediate cardiolipin species, and more so with resveratrol than with bezafibrate. Ratios were nevertheless profoundly abnormal in comparison to patients with intermediate Barth phenotypes. Discussion Main findings: study results There was no clinically important or statistically significant improvement in peak VO2 with bezafibrate compared to placebo. There were inconsistent findings for LVEF% by method of measurement; echocardiography showed a borderline improvement that cardiac MRI did not demonstrate. Longitudinal and circumferential strain measurements were better at rest with bezafibrate, but not at peak exercise. There were no clinically important or statistically significant improvements in core or fatigue QoL domains. Plasma cysteine was significantly improved with bezafibrate treatment. Plasma arginine also increased but not significantly. Neutrophil count was unaffected and there was no significant change in cardiolipin ratio in participants’ blood with bezafibrate. There were no significant period effects except for MLCL/L4-CL ratio and neutrophil count, both increased in the second period. In vitro incubation of Epstein–Barr virus-transformed patient lymphoblasts with either bezafibrate or resveratrol resulted in improved MLCL/L4-CL ratios, an effect that was more profound with resveratrol. Treatment with this drug also resulted in a more obvious increase in intermediate MLCL species. Strengths and limitations Strengths of the trial are: randomisation and placebo blinding; crossover design; excellent retention; completeness of the data, good adherence and IMP tolerance. There were several limitations. The sample size (outside our control) was very small, and interpretation of effects for many secondary outcomes was challenging. Longer treatment duration or a higher bezafibrate dose might have produced better outcomes. Bezafibrate may have induced adverse reactions in some participants, inadvertently causing unblinding. The group of participants randomised to receive bezafibrate first was older than the group randomised to the opposite order, which may explain period effects. The electron microscopic and mitochondrial assessments proved problematic and were not completed in vitro. Measurements of mitochondrial content and membrane potential were highly variable. Amino acid levels were not assayed after fasting. Echocardiography images during exercise testing were often suboptimal. Lessons for the future Magnetic resonance spectroscopy in children is still exploratory, and protocols need to be better validated, but it is considered very promising as a potential objective functional outcome. Cardiolipin profile is not a good outcome for research, although it is appropriate for diagnosis because the Barth cardiolipin profile is so extremely different from a normal profile. Electron microscopy measurements of mitochondria should not be considered as outcomes in future trials. Peak VO2 should be the preferred current primary outcome because it is resistant to bias compared to other functional outcomes. Conclusion The trial did not show a significant treatment effect for the primary outcome, peak VO2. Some secondary outcomes such as systolic function measured by echocardiography and amino acid levels provided some evidence of benefit. The trial provided insights about trial methods and conduct in the context of a very rare paediatric disease that should inform future studies. Trial registration This trial is registered as ISRCTN58006579. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/205/56) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 13. See the NIHR Funding and Awards website for further award information.

Abstract Gender identity refers to the consciousness of being a man, a woman or other condition. Although it is generally congruent with the sex assigned at birth, for some people it is not. If the incongruity is distressing, it is defined as gender dysphoria (GD). Here, we measured whole-genome DNA methylation by the Illumina © Infinium Human Methylation 850k array and reported its correlation with cortical thickness (CTh) in 22 transgender men (TM) experiencing GD versus 25 cisgender men (CM) and 28 cisgender women (CW). With respect to the methylation analysis, TM vs. CW showed significant differences in 35 CpGs, while 2155 CpGs were found when TM vs. CM were compared. With respect to correlation analysis, TM showed differences in methylation of CBLL1 and DLG1 genes that correlated with global and left hemisphere CTh. Both genes were hypomethylated in TM compared to the cisgender groups. Early onset TM showed a positive correlation between CBLL1 and several cortical regions in the frontal (left caudal middle frontal), temporal (right inferior temporal, left fusiform) and parietal cortices (left supramarginal and right paracentral). This is the first study relating CBLL1 methylation with CTh in transgender persons and supports a neurodevelopmental hypothesis of gender identity.

Abstract Prediction of spontaneous preterm birth in asymptomatic women remains a great challenge for the public health system. The aim of the study was to determine the informational value of EG-VEGF circulating levels for prediction of spontaneous preterm birth in the second and third trimesters in pregnant women at high risk for placenta-mediated complications. A prospective multicenter cohort study including 200 pregnant patients with five-serum sampling per patient. Women with spontaneous preterm birth have higher concentrations of serum EG-VEGF than uncomplicated patients at 24 weeks, 28 weeks and 32 weeks (p = 0.03, 0.02 and

Abstract Systemic sclerosis (SSc) is the most severe systemic autoimmune disease with currently no cure. Intravenous immunoglobulins (IVIg) are an attractive candidate in this disease to counteract inflammation and fibrosis but data are scarce and conflicting. This study, assessed the effects of IVIg in a murine HOCl-induced model of SSc. We showed that IVIg prevented skin inflammation and fibrosis, by mitigating the immune cell infiltration (p = 0.04), proinflammatory cytokines gene overexpression (IL1β, p = 0.04; TNFα, p = 0.04; IL6, p = 0.05), skin and dermal thickening (p = 0.003 at d21 and p = 0.0003 at d42), the expression markers of fibrosis, such as αSMA (p = 0.031 for mRNA and p = 0.05 for protein), collagen (p = 0.05 for mRNA and p = 0.04 for protein, p = 0.05 for the hydroxyproline content) and fibronectin (p = 0.033 for mRNA). Moreover, IVIg prevented HOCl-induced alterations in splenic cell homeostasis. When administered in curative mode, despite their ability to reduce skin and dermal thickness (p

Abstract Background Over the past decades, there has been a growing international interest in user involvement in healthcare research. However, evidence on the management and impact of patient and public involvement in Nordic healthcare research remains limited. Objective The aim was to explore and delineate the current state, practice, and impact of patient and public involvement in healthcare research across different areas of healthcare and patient populations in the Nordic countries. Methods We conducted a scoping review using nine scientific databases and gray literature from 1992–2023. Sources were categorized as empirical or non-empirical. We used the Guidance for Reporting Involvement of Patients and the Public Short Form 2 checklist for reporting of patient and public involvement in healthcare research and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. Results A total of 56 publications were included, consisting of 39 empirical and 17 non-empirical sources. Gray literature varied among countries and institutions encompassing different types of documents. We found an increase in the number of publications on patient and public involvement in Nordic healthcare research. This was evidenced by the growing number of references and institutional initiatives intended at involving the public, indicating the increasing emphasis on patient and public involvement in Nordic healthcare research. The terminology used to describe patient and public involvement varied over time. However, there has been a gradual narrowing down of terms as the concept of PPI has become more integrated into research practices, particularly with the involvement of funding agencies. Conclusion The utilization of patient and public involvement in Nordic healthcare research has substantially increased, proliferated, and gained widespread acceptance across diverse healthcare domains. The variety of approaches challenged our scoping review in terms of systematic description and impact. Patient and public involvement was applied in one or more research stages using different methodologies and terms. International agreement on terms and definitions is needed for reliable interpretation of the use of patient and public involvement in Nordic healthcare research.

Abstract Mitochondrial metabolism varies significantly between individuals of the same species and can influence animal performance, such as growth. However, growth rate is usually determined before the mitochondrial assay. The hypothesis that natural variation in mitochondrial metabolic traits is linked to differences in both previous and upcoming growth remains untested. Using biopsies to collect tissue in a non-lethal manner, we tested this hypothesis in a fish model (Dicentrarchus labrax) by monitoring individual growth rate, measuring mitochondrial metabolic traits in the red muscle, and monitoring the growth of the same individuals after the mitochondrial assay. Individual variation in growth rate was consistent before and after the mitochondrial assay; however, the mitochondrial traits that explained growth variation differed between the growth rates determined before and after the mitochondrial assay. While past growth was correlated with the activity of the cytochrome c oxidase, a measure of mitochondrial density, future growth was linked to mitochondrial proton leak respiration. This is the first report of temporal shift in the relationship between growth rate and mitochondrial metabolic traits, suggesting an among-individual variation in temporal changes in mitochondrial traits. Our results emphasize the need to evaluate whether mitochondrial metabolic traits of individuals can change over time.

Abstract We provide an original multi-stage approach identifying a gene signature to assess murine fibroblast polarization. Prototypic polarizations (inflammatory/fibrotic) were induced by seeded mouse embryonic fibroblasts (MEFs) with TNFα or TGFß1, respectively. The transcriptomic and proteomic profiles were obtained by RNA microarray and LC-MS/MS. Gene Ontology and pathways analysis were performed among the differentially expressed genes (DEGs) and proteins (DEPs). Balb/c mice underwent daily intradermal injections of HOCl (or PBS) as an experimental murine model of inflammation-mediated fibrosis in a time-dependent manner. As results, 1456 and 2215 DEGs, and 289 and 233 DEPs were respectively found in MEFs in response to TNFα or TGFß1, respectively. Among the most significant pathways, we combined 26 representative genes to encompass the proinflammatory and profibrotic polarizations of fibroblasts. Based on principal component analysis, this signature deciphered baseline state, proinflammatory polarization, and profibrotic polarization as accurately as RNA microarray and LC-MS/MS did. Then, we assessed the gene signature on dermal fibroblasts isolated from the experimental murine model. We observed a proinflammatory polarization at day 7, and a mixture of a proinflammatory and profibrotic polarizations at day 42 in line with histological findings. Our approach provides a small-size and convenient gene signature to assess murine fibroblast polarization.

Objective: This study investigates the feasibility of delivering inspiratory muscle training as part of the physical therapy treatment for patients with post-COVID dyspnoea. Design: Mixed-methods pilot study. Subjects/patients: Patients with complaints of dyspnoea after COVID-19 infection and their physical therapists. Methods: The Amsterdam University of Applied Sciences and the Amsterdam University Medical Centers conducted this study. Participants performed daily inspiratory muscle training at home for 6 weeks, consisting of 30 repetitions against a pre-set resistance. The primary outcome was feasibility assessed as acceptability, safety, adherence and patient- and professional experience obtained through diaries and semi-structured interviews. The secondary outcome was maximal inspiratory pressure. Results: Sixteen patients participated. Nine patients and 2 physical therapists partook in semi-structured interviews. Two patients dropped out before initiating the training. Adherence was 73.7%, and no adverse events occurred. Protocol deviations occurred in 29.7% of the sessions. Maximal inspiratory pressure changed from 84.7% of predicted at baseline to 111.3% at follow-up. Qualitative analysis identified barriers to training: ‘Getting acquainted with the training material’ and ‘Finding the right schedule’. Facilitators were: ‘Support from physical therapists’ and ‘Experiencing improvements’. Conclusion: Delivering inspiratory muscle training to patients with post-COVID dyspnoea seems feasible. Patients valued the simplicity of the intervention and reported perceived improvements. However, the intervention should be carefully supervised, and training parameters adjusted to individual needs and capacity. LAY ABSTRACT Many people who have recovered from a COVID-19 infection develop persistent shortness of breath, fatigue and difficulties with memories, learning new things or making decisions. This condition affects their daily life and is called post-COVID syndrome. Inspiratory muscle training is a technique that aims to help people to breathe more easily by strengthening and improving the coordination of breathing muscles. We undertook this study to determine if performing such training was possible for these patients. We interviewed 2 physiotherapists who provided the training and 9 of their patients. In addition, we looked into the diaries 16 patients kept about their training to learn about their experiences or unexpected (medical) problems they might have had with the training. We found that the training seemed reasonable since patients and their physiotherapists found it simple, and no negative experiences happened. However, patients said it helped if the physiotherapist supervised them during the training.

We investigated epidemiologic and molecular characteristics of healthcare-associated (HA) and community-associated (CA) Clostridioides difficile infection (CDI) among adult patients in Canadian Nosocomial Infection Surveillance Program hospitals during 2015–2019. The study encompassed 18,455 CDI cases, 13,735 (74.4%) HA and 4,720 (25.6%) CA. During 2015–2019, HA CDI rates decreased by 23.8%, whereas CA decreased by 18.8%. HA CDI was significantly associated with increased 30-day all-cause mortality as compared with CA CDI (p

Objetivo: identificar o perfil social e clínico de crianças e adolescentes com diabetes mellitus tipo 1. Método: pesquisa quantitativa, transversal e descritiva, desenvolvida com 81 responsáveis de crianças e adolescentes com diabetes mellitus tipo 1 entre março e setembro/2021, em dois centros de referência da Paraíba. A análise descritiva foi realizada com auxílio do software Statistical Package for the Social Science, versão 18. Resultados: predominantemente, os acompanhantes das crianças e adolescentes eram as próprias mães, 90,1%, e cerca de 40% viviam com renda familiar menor que um salário mínimo. Entre as crianças e adolescentes, 54% apresentaram valores elevados de hemoglobina glicada, mesmo estando em tratamento; 65,4% indicaram desconhecimento na forma correta de armazenamento da insulina, e 77,6% possuía lipohipertrofia. Conclusão: foram preponderantes a vulnerabilidade socioeconômica e o manejo clínico ineficaz do diabetes mellitus tipo 1 em crianças e adolescentes.

Rapid developments and methodological divides hinder the study of how scientific knowledge accumulates, consolidates and transfers to the public sphere. Our work proposes using Wikipedia, the online encyclopedia, as a historiographical source for contemporary science. We chose the high-profile field of gene editing as our test case, performing a historical analysis of the English-language Wikipedia articles on CRISPR. Using a mixed-method approach, we qualitatively and quantitatively analyzed the CRISPR article's text, sections and references, alongside 50 affiliated articles. These, we found, documented the CRISPR field's maturation from a fundamental scientific discovery to a biotechnological revolution with vast social and cultural implications. We developed automated tools to support such research and demonstrated its applicability to two other scientific fields-coronavirus and circadian clocks. Our method utilizes Wikipedia as a digital and free archive, showing it can document the incremental growth of knowledge and the manner scientific research accumulates and translates into public discourse. Using Wikipedia in this manner compliments and overcomes some issues with contemporary histories and can also augment existing bibliometric research.

During a mouse plague in early 2021, a farmer from New South Wales, Australia, sought treatment for aseptic meningitis and was subsequently diagnosed with locally acquired lymphocytic choriomeningitis virus infection. Whole-genome sequencing identified a divergent and geographically distinct lymphocytic choriomeningitis virus strain compared with other published sequences.

Abstract Considerable progress has been made in the treatment of coronary bifurcation stenosis. Anatomical characteristics of the vessel and lesion, however, fail to give information about the functional significance of the bifurcation stenosis. To the best of our knowledge, there is no study that systematically establishes the baseline functional significance of coronary stenosis and its effect on procedural and clinical outcomes. Patients with significant angiographic bifurcation lesions defined as diameter stenosis > 50% in main vessel and/or side branch were included. FFR was performed in main vessel (MV) and side branch (SB) before and after percutaneous coronary intervention (PCI). 169 patients from Fiesta study (derivation cohort) and 555 patients from prospective bifurcation registry (clinical effect cohort) were analyzed to validate angiographic prediction score (BFSS) used to determine the potentially functional significance of coronary bifurcation stenosis. Bifurcation functional significance score (including the following parameters—SYNTAX ≥ 11, SB/MB BARI score, MV %DS ≥ 55%, main branch (MB) %DS ≥ 65%, lesion length ≥ 25 mm) with a maximum value of 11 was developed. A cut-off value of 6.0 was shown to give the best discriminatory ability—with accuracy 87% (sensitivity 77%, specificity 96%, p

Abstract Calcium sparks are involved in major physiological and pathological processes in vertebrate muscles but have never been characterized in invertebrates. Here, dynamic confocal imaging on intact skeletal muscle cells isolated enzymatically from the adult honey bee legs allowed the first spatio-temporal characterization of subcellular calcium release events (CREs) in an insect species. The frequency of CREs, measured in x–y time lapse series, was higher than frequencies usually described in vertebrates. Honey bee CREs had a larger spatial spread at half maximum than their vertebrate counterparts and a slightly ellipsoidal shape, two characteristics that may be related to ultrastructural features specific to invertebrate cells. In line-scan experiments, the histogram of CREs’ duration followed a bimodal distribution, supporting the existence of both sparks and embers. Unlike in vertebrates, embers and sparks had similar amplitudes, a difference that could be related to genomic differences and/or excitation–contraction coupling specificities in honey bee skeletal muscle fibres. The first characterization of CREs from an arthropod which shows strong genomic, ultrastructural and physiological differences with vertebrates may help in improving the research field of sparkology and more generally the knowledge in invertebrates cell Ca2+ homeostasis, eventually leading to a better understanding of their roles and regulations in muscles but also the myotoxicity of new insecticides targeting ryanodine receptors.

Abstract Motor imagery (MI) is usually facilitated when performed in a congruent body position to the imagined movement, as well as after actual execution (AE). A lower-limb amputation (LLA) results in important structural and functional changes in the sensorimotor system, which can alter MI. In this study, we investigated the effects of body position and AE on the temporal characteristics of MI in people with LLA. Ten participants with LLA (mean age = 59.6 ± 13.9 years, four females) and ten gender- and age-matched healthy control participants (mean age = 60.1 ± 15.4 years, four females) were included. They performed two locomotor-related tasks (a walking task and the Timed Up and Go task) while MI times were measured in different conditions (in congruent/incongruent positions and before/after AE). We showed that MI times were significantly shorter when participants imagined walking in a congruent-standing position compared to an incongruent-sitting position, and when performing MI after actual walking compared to before, in both groups. Shorter MI times in the congruent position and after AE suggest an improvement of MI’s temporal accuracy (i.e. the ability to match AE time during MI) in healthy individuals but not in the LLA group.

Abstract Background The peripheral venous catheter is the most frequently used medical device in hospital care to administer intravenous treatment or to take blood samples by introducing a catheter into a vein. The aim of this study was to examine the effect of motor imagery associated with actual training on the learning of peripheral venous catheter insertion into a simulated venous system. Method This was a prospective monocentre study in 3rd year medical students. Forty medical students were assigned to the experimental group (n = 20) performing both real practice and motor imagery of peripheral venous catheter insertion or to the control group (n = 20) trained through real practice only. We also recruited a reference group of 20 professional nurses defining the benchmark for a target performance. Results The experimental group learned the peripheral venous catheter insertion faster than the control group in the beginning of learning phase (p

From November 2018 through July 2019, an outbreak of Rift Valley fever in humans occurred in Mayotte, France; 142 cases were confirmed. Exposure to animals or their biological fluid was reported by 73% of patients. Health authorities have been implementing control measures, including veterinary surveys, vector control interventions, and prevention measures.

Background: Human challenge studies involve the deliberate exposure of healthy volunteers to an infectious micro-organism in a highly controlled and monitored way. They are used to understand infectious diseases and have contributed to the development of vaccines. In early 2020, the UK started exploring the feasibility of establishing a human challenge study with SARS-CoV-2. Given the significant public interest and the complexity of the potential risks and benefits, it is vital that public views are considered in the design and approval of any such study and that investigators and ethics boards remain accountable to the public. Methods: Mixed methods study comprising online surveys conducted with 2,441 UK adults and in-depth virtual focus groups with 57 UK adults during October 2020 to explore the public’s attitudes to a human challenge study with SARS-CoV-2 taking place in the UK. Results: There was overall agreement across the surveys and focus groups that a human challenge study with SARS-CoV-2 should take place in the UK. Transparency of information, trust and the necessity to provide clear information on potential risks to study human challenge study participants were important. The perceived risks of taking part included the risk of developing long-term effects from COVID, impact on personal commitments and mental health implications of isolation. There were a number of practical realities to taking part that would influence a volunteer’s ability to participate (e.g. Wi-Fi, access to exercise, outside space and work, family and pet commitments). Conclusions: The results identified practical considerations for teams designing human challenge studies. Recommendations were grouped: 1) messaging to potential study participants, 2) review of the protocol and organisation of the study, and 3) more broadly, making the study more inclusive and relevant. This study highlights the value of public consultation in research, particularly in fields attracting public interest and scrutiny.

Cerenkov-induced photodynamic therapy (CR-PDT) with the use of Gallium-68 (68Ga) as an unsealed radioactive source has been proposed as an alternative strategy to X-ray-induced photodynamic therapy (X-PDT). This new strategy still aims to produce a photodynamic effect with the use of nanoparticles, namely, AGuIX. Recently, we replaced Gd from the AGuIX@ platform with Terbium (Tb) as a nanoscintillator and added 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenylporphyrin (P1) as a photosensitizer (referred to as AGuIX@Tb-P1). Although Cerenkov luminescence from 68Ga positrons is involved in nanoscintillator and photosensitizer activation, the cytotoxic effect obtained by PDT remains controversial. Herein, we tested whether free 68Ga could substitute X-rays of X-PDT to obtain a cytotoxic phototherapeutic effect. Results were compared with those obtained with AGuIX@Gd-P1 nanoparticles. We showed, by Monte Carlo simulations, the contribution of Tb scintillation in P1 activation by an energy transfer between Tb and P1 after Cerenkov radiation, compared to the Gd-based nanoparticles. We confirmed the involvement of the type II PDT reaction during 68Ga-mediated Cerenkov luminescence, id est, the transfer of photon to AGuIX@Tb-P1 which, in turn, generated P1-mediated singlet oxygen. The effect of 68Ga on cell survival was studied by clonogenic assays using human glioblastoma U-251 MG cells. Exposure of pre-treated cells with AGuIX@Tb-P1 to 68Ga resulted in the decrease in cell clone formation, unlike AGuIX@Gd-P1. We conclude that CR-PDT could be an alternative of X-PDT.

Enquadramento: A diabetes mellitus tipo 1 requer autonomia do adolescente para a realização do autocuidado. Objetivo: Analisar o processo de construção da autonomia para o autocuidado de adolescentes com diabetes mellitus tipo 1. Metodologia: Pesquisa descritiva-exploratória com nove adolescentes com diabetes tipo 1, através de entrevistas semiestruturadas e dados interpretados pela análise temática indutiva. Resultados: O processo de construção da autonomia do adolescente com diabetes inicia com o interesse em procurar conhecimento sobre a doença e tratamento, aprimorado pelo apoio da rede social, potencializando a confiança em si para assumir o seu autocuidado. Dificuldades em controlar a dieta, ter acesso aos materiais para insulinoterapia e falta de segurança para manuseá-los constituem obstáculos para essa construção. Conclusão: É fundamental apoiar esses adolescentes na construção da autonomia para o autocuidado a fim de superar as dificuldades na gestão da diabetes e prevenir complicações que podem comprometer a sua qualidade de vida e gerar custo ao sistema de saúde.

Considering the individual characteristics of positron emission tomography (PET) and optical imaging (OI) in terms of sensitivity, spatial resolution, and tissue penetration, the development of dual imaging agents for bimodal PET/OI imaging is a growing field. A current major breakthrough in this field is the design of monomolecular agent displaying both a radioisotope for PET and a fluorescent dye for OI. We took advantage of the multifunctionalities allowed by a clickable C-glycosyl scaffold to gather the different elements. We describe, for the first time, the synthesis of a cyanine-based dual PET/OI imaging probe based on a versatile synthetic strategy and its direct radiofluorination via [18F]F-C bond formation. The non-radioactive dual imaging probe coupled with two c(RGDfK) peptides was evaluated in vitro and in vivo in fluorescence imaging. The binding on αvβ3 integrin (IC50 = 16 nM) demonstrated the efficiency of the dimeric structure and PEG linkers in maintaining the affinity. In vivo fluorescence imaging of U-87 MG engrafted nude mice showed a high tumor uptake (40- and 100-fold increase for orthotopic and ectopic brain tumors, respectively, compared to healthy brain). In vitro and in vivo evaluations and resection of the ectopic tumor demonstrated the potential of the conjugate in glioblastoma cancer diagnosis and image-guided surgery.

Abstract Objective The primary objective of this non-randomised phase II study was to evaluate the combination of systemic chemotherapy plus cetuximab after complete cytoreductive surgery (CCS) for treatment of isolated colorectal peritoneal carcinoma (CRPC). This multicentre, prospective phase II clinical trial was conducted in seven national cancer referral centres, however research published during study recruitment indicated cetuximab treatment as ineffective in patients with mutated KRAS genes, leading to an additional exclusion criterion to the current protocol, excluding patients with mutated KRAS genes. This significantly impacted recruitment and the study did not achieve the necessary recruitment of 46 patients. Results Fourteen patients underwent CCS and were included in the study, however one did not provide informed consent and another received only one cycle of chemotherapy leading to 12 patients in the per protocol population for analysis. Adjuvant Folfox Cetuximab was administered when CCS was achieved for patients > 18 years with histologically proven CRPC and no other metastatic disease (liver, lungs, lymphadenopathy, etc.). CRPC median index was 5.00 (range: 1–17). Median PFS was 12.3 months [95% CI (3.7–28.2)] with 8.3% [95% CI (0.5–31.1)] and 0% PFS at 3 and 5 years respectively. Median OS was 43.4 months [95% CI (16.8–60)]. Trial registration Clinical Trials NCT00766142, October 3, 2008. Retrospectively registered

Abstract Background Phenylalanine hydroxylase (PAH) deficiency is one of 31 targeted inherited metabolic diseases (IMD) for the Canadian Inherited Metabolic Diseases Research Network (CIMDRN). Early diagnosis and initiation of treatment through newborn screening has gradually shifted treatment goals from the prevention of disabling complications to the optimization of long term outcomes. However, clinical evidence demonstrates that subtle suboptimal neurocognitive outcomes are present in the early and continuously diet-treated population with PAH deficiency. This may be attributed to variation in blood phenylalanine levels to outside treatment range and this, in turn, is possibly due to a combination of factors; disease severity, dietary noncompliance and differences in practice related to the management of PAH deficiency. One of CIMDRN’s goals is to understand current practices in the diagnosis and management of PAH deficiency in the pediatric population, from the perspective of both health care providers and patients/families. Objectives We investigated Canadian metabolic dietitians’ perspectives on the nutritional management of children with PAH deficiency, awareness of recently published North American treatment and nutritional guidelines in relation to PAH deficiency, and nutritional care practices within and outside these guidelines. Methods We invited 33 dietitians to participate in a survey, to ascertain their use of recently published guidelines and their practices in relation to the nutritional care of pediatric patients with PAH deficiency. Results We received 19 responses (59% response rate). All participants reported awareness of published guidelines for managing PAH deficiency. To classify disease severity, 89% of dietitians reported using pre-treatment blood phenylalanine (Phe) levels, alone or in combination with other factors. 74% of dietitians reported using blood Phe levels ≥360 μmol/L (6 mg/dL) as the criterion for initiating a Phe-restricted diet. All respondents considered 120-360 μmol/L (2–6 mg/dL) as the optimal treatment range for blood Phe in children 0–9 years old, but there was less agreement on blood Phe targets for older children. Most dietitians reported similar approaches to diet assessment and counseling: monitoring growth trends, use of 3 day diet records for intake analysis, individualization of diet goals, counseling patients to count grams of dietary natural protein or milligrams of dietary Phe, and monitoring blood Phe, tyrosine and ferritin. Conclusion While Canadian dietitians’ practices in managing pediatric PAH deficiency are generally aligned with those of the American College of Medical Genetics and Genomics (ACMG), and with the associated treatment and nutritional guidelines from Genetic Metabolic Dietitians International (GMDI), variation in many aspects of care reflects ongoing uncertainty and a need for robust evidence.

O objetivo deste estudo foi investigar a relação entre idade e tempo de prática com a autoeficácia em atletas de voleibol segundo o sexo e a relação entre idade e tempo de prática com a autoeficácia geral, bem como verificar como esses aspectos impactam na crença sobre a eficácia de jogadores de voleibol. Atletas de voleibol de alto rendimento (n = 300), com média de idade de 24,88 ± 5,51 anos e tempo médio de experiência de 11,12 ± 5,24 anos, responderam a Escala de Autoeficácia de Voleibol e a Escala de Autoeficácia Geral Percebida. A idade e tempo de prática estão correlacionados com a Autoeficácia Global no Voleibol e com as dimensões Autoeficácia no Jogo, Autoeficácia Defensiva no Voleibol e Autoeficácia Ofensiva no Voleibol de atletas masculinos, feminino, masculino e feminino. A Autoeficácia Geral Percebida está relacionada à idade e ao tempo de prática de atletas femininas e considerando ambos os sexos. Essas variáveis representam aspectos importantes para a construção e solidificação de crenças positivas de atletas de ambos os sexos quanto às suas habilidades específicas e das mulheres para a autoeficácia geral na vida. Palavras-chave: autoeficácia, voleibol, atletas.

Pre-pubertal murine models of acute colitis are lacking. Magnetic resonance colonography (MRC) is a promising minimally invasive tool to assess colitis. We aimed to: 1/ Adapt a model of acute experimental colitis to pre-pubertal rats and determine whether MRC characteristics correlate with histological inflammation. 2/ Test this model by administering a diet supplemented in transforming growth factor β2 to reverse inflammation. Twenty-four rats were randomized at weaning to one of 3 groups: Trinitrobenzene Sulfonic Acid (TNBS) group (n = 8) fed a standard diet, that received an intra-rectal 60 mg/kg dose of TNBS-ethanol; Control group (n = 8) fed standard diet, that received a dose of intra-rectal PBS; TNBS+MODULEN group (n = 8) that received a dose of TNBS and were exclusively fed MODULEN-IBD® after induction of colitis. One week after induction of colitis, rats were assessed by MRC, colon histopathology and inflammation markers (Interleukin 1β, Tumor necrosis factor α, Nitric Oxide Synthase 2 and Cyclooxygenase 2). TNBS induced typical features of acute colitis on histopathology and MRC (increased colon wall thickness, increased colon intensity on T2-weighted images, target sign, ulcers). Treatment with MODULEN-IBD® did not reduce signs of colitis on MRC. Inflammatory marker expression did not differ among study groups.

Brazil has been the benchmark for volleyball performance for at least two decades, providing a unique context to examine expertise development. This study examined the variation in body size, functional capacities, motivation for achievement, competitiveness, and deliberate practice of youth volleyball players associated with differences in biological maturity status, chronological age, and accumulated deliberate volleyball practice, adopting a Bayesian multilevel modeling approach. We considered 68 female and 94 male adolescent players (14.2 years, 90% confidence interval: 12.7 to 16.0). Players were grouped by the onset of deliberate volleyball practice as related to biologic maturation milestones [pre-puberty deliberate practice onset (12% of the sample), mid-puberty deliberate practice onset (51% of the sample), and late-puberty deliberate practice onset (37% of the sample). There was substantial variation in body dimensions and functional performance by gender. There was no variation by gender for motivation for deliberate practice and motivation for achievement and competitiveness. The young volleyball players appeared to be highly motivated and committed to deliberate practice, achievement, and competitiveness. Alignment of chronological age, biological maturation, and accumulated training experience allow more in-depth insights into young volleyball players' development, providing sounder support for coaches´ decisions.

Pre-pubertal murine models of acute colitis are lacking. Magnetic resonance colonography (MRC) is a promising minimally invasive tool to assess colitis. We aimed to: 1/ Adapt a model of acute experimental colitis to pre-pubertal rats and determine whether MRC characteristics correlate with histological inflammation. 2/ Test this model by administering a diet supplemented in transforming growth factor β2 to reverse inflammation. Twenty-four rats were randomized at weaning to one of 3 groups: Trinitrobenzene Sulfonic Acid (TNBS) group (n = 8) fed a standard diet, that received an intra-rectal 60 mg/kg dose of TNBS-ethanol; Control group (n = 8) fed standard diet, that received a dose of intra-rectal PBS; TNBS+MODULEN group (n = 8) that received a dose of TNBS and were exclusively fed MODULEN-IBD® after induction of colitis. One week after induction of colitis, rats were assessed by MRC, colon histopathology and inflammation markers (Interleukin 1β, Tumor necrosis factor α, Nitric Oxide Synthase 2 and Cyclooxygenase 2). TNBS induced typical features of acute colitis on histopathology and MRC (increased colon wall thickness, increased colon intensity on T2-weighted images, target sign, ulcers). Treatment with MODULEN-IBD® did not reduce signs of colitis on MRC. Inflammatory marker expression did not differ among study groups.

BackgroundHigh-risk human papillomavirus HPV (HR-HPV) modifies cervical cancer risk in people living with HIV, yet African populations are under-represented. We aimed to compare the frequency, multiplicity and consanguinity of HR-HPVs in HIV-negative and HIV-positive Zimbabwean women.MethodsThis was a cross-sectional study consisting of women with histologically confirmed cervical cancer attending Parirenyatwa Group of Hospitals in Harare, Zimbabwe. Information on HIV status was also collected for comparative analysis. Genomic DNA was extracted from 258 formalin fixed paraffin embedded tumour tissue samples, and analysed for 14 HR-HPV genotypes. Data was analysed using Graphpad Prism and STATA.ResultsForty-five percent of the cohort was HIV-positive, with a median age of 51 (IQR = 42-62) years. HR-HPV positivity was detected in 96% of biospecimens analysed. HPV16 (48%), was the most prevalent genotype, followed by HPV35 (26%), HPV18 (25%), HPV58 (11%) and HPV33 (10%), irrespective of HIV status. One third of the cohort harboured a single HPV infection, and HPV16 (41%), HPV18 (21%) and HPV35 (21%) were the most prevalent. HIV status did not influence the prevalence and rate of multiple HPV infections (p>0.05). We reported significant (pConclusionWe found that HIV does not influence the frequency, multiplicity and consanguinity of HR-HPV in cervical cancer. For the first time, we report high prevalence of HPV35 among women with confirmed cervical cancer in Zimbabwe, providing additional evidence of HPV diversity in sub-Saharan Africa. The data obtained here probes the need for larger prospective studies to further elucidate HPV diversity and possibility of selective pressure on genotypes.

Objective: to analyze the management of care for children/adolescents with chronic diseases in the health care network, based on the experiences of families in the search for the care of their child. Method: a qualitative research, carried out with ten relatives of children/adolescents with chronic diseases, residents of the city of João Pessoa, Paraiba, Brazil. Data was collected from November 2017 to June 2018 through semi-structured interviews and submitted to inductive thematic analysis. Results: the health care network for children/adolescents with chronic diseases is disjointed and the care actions fragmented; families design their own therapeutic itineraries and do not receive support from e professionals/services in care management. Conclusion: disarticulation in the planning of care actions in health care networks, combined with punctual and discontinuous care for children/adolescents with chronic diseases and their family weaken and impoverish care management.

OmpA, a protein commonly found in the outer membrane of Gram-negative bacteria, has served as a paradigm for the study of β-barrel proteins for several decades. In Escherichia coli, OmpA was previously reported to form complexes with RcsF, a surface-exposed lipoprotein that triggers the Rcs stress response when damage occurs in the outer membrane and the peptidoglycan. How OmpA interacts with RcsF and whether this interaction allows RcsF to reach the surface has remained unclear. Here, we integrated in vivo and in vitro approaches to establish that RcsF interacts with the C-terminal, periplasmic domain of OmpA, not with the N-terminal β-barrel, thus implying that RcsF does not reach the bacterial surface via OmpA. Our results suggest a novel function for OmpA in the cell envelope: OmpA competes with the inner membrane protein IgaA, the downstream Rcs component, for RcsF binding across the periplasm, thereby regulating the Rcs response.

Samenvatting In het verpleeghuis en bij de thuiszorg komen veel cliënten met probleemgedrag voor. Met name als hierbij persoonlijkheidsstoornissen of maladaptieve persoonlijkheidstrekken een rol spelen, leidt dit vaak tot een verhoogde en specifieke zorgbehoefte en tot meer psychisch lijden bij zowel de cliënt als de mantelzorger; dit omdat hun gedrag niet altijd als een gevolg of uiting van hun persoonlijkheid wordt gezien. Aan de hand van twee casussen bespreken we de gevolgen van de persoonlijkheidsaspecten voor de multidisciplinaire zorgverlening, de rol van externe ondersteuning in de vorm van psychiatrische consultatie en de noodzaak tot vergroting van kennis en kunde van het verzorgend personeel. Abstract Problem behavior is frequently present in older people living in nursing homes or needing home care services. When Personality disorders or maladaptive traits are involved these older people need specific care. In addition, they and their carers might experience psychological suffering as their behavior is not always properly recognized as the result of their personality. The importance of multidisciplinary teamwork, the role of psychiatric consultation given by an elderly psychiatrist as well as the need for upgrading the knowhow within the care sector itself is discussed using 2 vignettes

Recent debates on insect decline require sound assessments on the relative drivers that may negatively impact insect populations. Often, baseline data rely on insect monitorings that integrate catches over long time periods. If, however, effects of time-critical environmental factors (e.g., light pollution) are of interest, higher temporal resolution of insect data is required during very specific time intervals (e.g., between dusk and dawn). Conventional time-critical insect trapping is labour-intensive (manual activation/deactivation) and temporally inaccurate as not all traps can be serviced synchronically at different sites. Also, temporal shifts of environmental conditions (e.g., sunset/sunrise) are not accounted for. We present a battery-driven automated insect flight-interception trap which samples insects during seven user-defined time intervals. A commercially available flight-interception trap is fitted to a turntable containing eight positions, seven of them holding cups and one consisting of a pass-through hole. While the cups sample insects during period of interest, the pass-through hole avoids unwanted sampling during time-intervals not of interest. Comparisons between two manual and two automated traps during 71 nights in 2018 showed no difference in caught insects. A study using 20 automated traps during 104 nights in 2019 proved that the automated flight-interception traps are reliable. The automated trap opens new research and application possibilities as arbitrary insect-sampling intervals can be defined. The trap proves efficient, saving manpower and associated costs as activation/deactivation is required only every seven sampling intervals. In addition, the timing of the traps is accurate, as all traps sample at exactly the same intervals and ensure comparability. The automated trap is low maintenance and robust due to straightforward technical design. It can be controlled manually or via smartphone through a Bluetooth connection. Full construction details are given in Appendices.

Abstract Objective This study describes a restriction fragment polymorphism protocol for rapidly screening the polymorphism SLCO1B1 c.1929A>C in genomic DNA samples. The polymorphism SLCO1B1 c.1929A>C has been associated with increased activity resulting in increased hepatic uptake of drugs. Currently SLCO1B1 c.1929A>C is genotyped using direct sequencing techniques and 5′ nuclease based assays which can be cost prohibiting in resource limited settings. The aim of this study therefore was to design and validate a cost effective RFLP for genotyping the SLCO1B1 c.1929A>C polymorphism. This study was designed to investigate the effect of the polymorphism SLCO1B1 c.1929A>C on interindividual variability in rosuvastatin pharmacokinetics in healthy volunteers of African descent. Results We describe a restriction fragment length polymorphism method to genotype SLCO1B1 c.1929A>C polymorphism using the restriction enzyme Ase1. A student’s t test with Welch correction was used to establish association between the SLCO1B1 c.1929A>C variant and rosuvastatin exposure. The frequency of the SLCO1B1 c.1929C allele amongst Zimbabweans was 6%. The SLCO1B1 c.1929C allele was associated with a 75% reduction (P C may therefore play a significant role in rosuvastatin response. The RFLP method is quick and cost effective.

Abstract Some obese subjects overeat lipid-rich foods. The origin of this eating behavior is unknown. We have here tested the hypothesis that these subjects could be characterized by an impaired fatty taste sensitivity linked to a change in the gustatory papillae microbial and salivary environment. The composition of microbiota and saliva surrounding the circumvallate papillae was analyzed in combination with the orosensory lipid detection threshold in normal weight (NW) and obese (O) adults. Microbial architecture was similar to what was known in feces, but with an increased frequency of Proteobacteria. No difference in the orosensory sensitivity to lipids and composition of oral microbiota and saliva was observed between NW and O subjects. By contrast, specific bacterial and salivary signatures were found in lipid non-tasters, irrespectively of BMI. A multivariate approach highlighted that the salivary flow, lysozyme activity, total antioxidant capacity and TM7 bacterial family discriminated between tasters and non-tasters. Subgroup analysis of obese tasters (OT) versus obese non-tasters (ONT) identified specific bacterial metabolic pathways (i.e. phosphotransferase and simple sugar transport systems) as being higher in ONT. Altogether with the identification of a set of significant salivary variables, our study suggests that an “obese tongue” phenotype is associated with decreased orosensory sensitivity to lipids in some obese subjects.

Abstract Performing everyday actions requires fine postural control, which is a major focus of functional rehabilitation programs. Among the various range of training methods likely to improve balance and postural stability, motor imagery practice (MIP) yielded promising results. Transcranial direct current stimulation (tDCS) applied over the primary motor cortex was also found to potentiate the benefits of MIP on upper-limb motor tasks. Yet, combining both techniques has not been tested for tasks requiring fine postural control. To determine the impact of MIP and the additional effects of tDCS, 14 participants performed a postural control task before and after two experimental (MIP + anodal or sham tDCS over the primary motor cortex) and one control (control task + sham tDCS) conditions, in a double blind randomized study. Data revealed a significant decrease of the time required to perform the postural task. Greater performance gains were recorded when MIP was paired with anodal tDCS and when the task involved the most complex postural adjustments. Altogether, findings highlight short-term effects of MIP on postural control and suggest that combining MIP with tDCS might also be effective in rehabilitation programs for regaining postural skills in easily fatigable persons and neurologic populations.

Objetivo : identificar la red y el apoyo en la percepción del niño con enfermedad crónica. Método : investigación cualitativa, realizada entre noviembre de 2012 y junio de 2013, en un hospital público de Paraíba, Brazil, con ocho niños con diagnóstico de enfermedad crónica. Se utilizó una adaptación del procedimiento del diseño-historia con tema. Los datos fueron interpretados por medio de análisis temático. Resultados: en algunos momentos de la vida, el niño recibe diferentes tipos de apoyo, que son ofrecidos por vínculos fortalecidos que componen su red social. Sin embargo, ni siempre esta red se mostró fortalecida y capaz de ofrecer el apoyo necesario al enfrentamiento adecuado de la enfermedad. Conclusión: los profesionales de salud necesitan direccionar su mirada para los niños, oyéndolos en sus singularidades y ayudando a identificar eslabones en su red social que puedan proporcionar el apoyo que necesitan para enfrentar la enfermedad crónica.

Hypochlorous acid (HOCl; bleach) is a powerful weapon used by our immune system to eliminate invading bacteria. Yet the way HOCl actually kills bacteria and how they defend themselves from its oxidative action have only started to be uncovered. As this molecule induces both protein oxidation and aggregation, bacteria need concerted efforts of chaperones and antioxidants to maintain proteostasis during stress. Recent advances in the field identified several stress-activated chaperones, like Hsp33, RidA, and CnoX, which display unique structural features and play a central role in protecting the bacterial proteome during HOCl stress.

The African Pharmacogenomics Consortium (APC) was formally launched on the 6th September 2018. This white paper outlines its vision, and objectives towards addressing challenges of conducting and applying pharmacogenomics in Africa and identifies opportunities for advancement of individualized drugs use on the continent. Africa, especially south of the Sahara, is beset with a huge burden of infectious diseases with much co-morbidity whose multiplicity and intersection are major challenges in achieving the sustainable development goals (SDG), SDG3, on health and wellness. The profile of drugs commonly used in African populations lead to a different spectrum of adverse drug reactions (ADRs) when compared to other parts of the world. Coupled with the genetic diversity among Africans, the APC is established to promote pharmacogenomics research and its clinical implementation for safe and effective use of medicine in the continent. Variation in the way patients respond to treatment is mainly due to differences in activity of enzymes and transporters involved in pathways associated with each drug’s disposition. Knowledge of pharmacogenomics, therefore, helps in identifying genetic variants in these proteins and their functional effects. Africa needs to consolidate its pharmacogenomics expertise and technological platforms to bring pharmacogenomics to use.

Fisheries compete with seabirds for vanishing marine resources, but also produce fishery waste consumed by seabirds. Marine birds may therefore avoid or seek fishing vessels, and have evolved complex, plastic behavioural responses to vessel presence. Understanding these responses is essential to the conservation of a globally declining seabird community. We studied Cape gannets (Morus capensis), which compete with fisheries for reduced sardine (Sardinops sagax) resources in the Benguela upwelling region off South Africa. Using bird-borne GPS trackers coupled with newly-developed ship-radar detectors we show that foraging gannets seldom attended fishing vessels. Rather, they switched from eating scarce sardines or energetically-poor fishery waste to targeting locally abundant saury (Scomberesox saurus). This pelagic fish is brought into the seascape by warm water influx, and is not commercially exploited by fisheries. Cape gannets thereby show dietary plasticity, allowing them to maintain adult body condition and chick growth rates. This diet switch is a strong indicator that Cape gannets forage in an ecologically perturbed marine environment.

Seabirds are well known to be attracted by fishing boats to forage on offal and baits. We used recently developed loggers that record accurate GPS position and detect the presence of boats through their radar emissions to examine how albatrosses use Area Restricted Search (ARS) and if so, have specific ARS behaviours, when attending boats. As much as 78.5% of locations with a radar detection (contact with boat) during a trip occurred within ARS: 36.8% of all large-scale ARS (n = 212) and 14.7% of all small-scale ARS (n = 1476) were associated with the presence of a boat. During small-scale ARS, birds spent more time and had greater sinuosity during boat-associated ARS compared with other ARS that we considered natural. For, small-scale ARS associated with boats, those performed over shelves were longer in duration, had greater sinuosity, and birds spent more time sitting on water compared with oceanic ARS associated with boats. We also found that the proportion of small-scale ARS tend to be more frequently nested in larger-scale ARS was higher for birds associated with boats and that ARS behaviour differed between oceanic (tuna fisheries) and shelf-edge (mainly Patagonian toothfish fisheries) habitats. We suggest that, in seabird species attracted by boats, a significant amount of ARS behaviours are associated with boats, and that it is important to be able to separate ARS behaviours associated to boats from natural searching behaviours. Our study suggest that studying ARS characteristics should help attribute specific behaviours associated to the presence of boats and understand associated risks between fisheries.

BackgroundOral antithrombotic (AT) drugs, which include antiplatelet and anticoagulant therapies, are widely implicated in serious preventable bleeding events. Avoiding inappropriate oral AT combinations is a major concern. Numerous practical guidelines have been released; a document to enhance prescriptions of oral AT combinations for adults would be of great help.ObjectiveTo synthesize guidelines on the prescription of oral AT combinations in adults and to create a prescription support-tool for clinicians about chronic management (≥ one month) of oral AT combinations.MethodsA systematic review of guidelines published between January 2012 and April 2017, in English or in French, from Trip database, Guideline International Network and PubMed, dealing with the prescription of oral ATs in adults was conducted. In-hospital management of ATs, bridging therapy and switches of ATs were not considered. Some specific topics requiring specialized follow-up (cancer, auto-immune disease, haemophilia, HIV, paediatrics and pregnancy) were excluded. Last update was made in November 2018.ResultsA total of 885 guidelines were identified and 70 met the eligibility criteria. A prescription support-tool summarizing medical conditions requiring chronic management of oral AT combinations in adults with drug types, dosage and duration, on a double-sided page, was provided and tested by an external committee of physicians. The lack of specific guidelines for old people (age 75 years and older) is questioned considering the specific vulnerability of this age group to serious bleedings.ConclusionsRecommendations on prescriptions about chronic management of oral AT combinations in adults were mainly consensual but dispersed in numerous guidelines according to the medical indication. We provide a prescription support-tool for clinicians. Further studies are needed to assess the impact of this tool on appropriate prescribing and the prevention of serious adverse drug events.

Traditionally, commercial testing for vaccine efficacy has relied on the mass infection of vaccinated and unvaccinated animals and the comparison of mortality prevalence and incidence. For some infection models where disease does not cause mortality this approach to testing vaccine efficacy is not useful. Additionally, in fish experimental studies on vaccine efficacy and immune response the norm is that several individuals are lethally sampled at sequential timepoints, and results are extrapolated to represent the kinetics of immune and disease parameters of an individual fish over the entire experimental infection period. In the present study we developed a new approach to vaccine testing for viremic viruses in fish by following the same individuals over the course of a DNA vaccination and experimental infection through repeated blood collection and analyses. Injectable DNA vaccines are particularly efficient against viral disease in fish. To date, two DNA vaccines have been authorised for use in fish farming, one in Canada against Infectious Haemorrhagic Necrotic virus and more recently one in Europe against Salmon Pancreatic Disease virus (SPDv) subtype 3. In the current study we engineered and used an experimental DNA vaccine against SPDv subtype 1. We measured viremia using a reporter cell line system and demonstrated that the viremia phase was completely extinguished following DNA vaccination. Differences in viremia infection kinetics between fish in the placebo group could be related to subsequent antibody levels in the individual fish, with higher antibody levels at terminal sampling in fish showing earlier viremia peaks. The results indicate that sequential non-lethal sampling can highlight associations between infection traits and immune responses measured at asynchronous timepoints and, can provide biological explanations for variation in data. Similar to results observed for the SPDv subtype 3 DNA vaccine, the SPDv subtype 1 DNA vaccine also induced an interferon type 1 response after vaccination and provided high protection against SPDv under laboratory conditions when fish were challenged at 7 weeks post-vaccination.

O objetivo do estudo foi analisar o nível de desempenho técnico-tático de jogadores de voleibol dos escalões de formação em Santa Catarina. Participaram no estudo 271 jogadores de 24 equipas de voleibol, finalistas do campeonato estadual de 2010, dos escalões mirim, infantil e infanto-juvenil. Os jogos foram filmados e, posteriormente, as ações técnico-táticas analisadas por meio do Instrumento de Avaliação do Desempenho Técnico-Tático no Voleibol. Na análise dos dados foram utilizadas a estatística descritiva e inferencial através do Programa SPSS versão 23, para apresentar os níveis de desempenho dos jogadores e associá-los com o género e o escalão competitivo. No desempenho global, os resultados mostraram que a maioria dos jogadores apresentou nível adequado de desempenho técnico-tático, com destaque para as componentes ajustamento e eficiência. Nas componentes tomada de decisão e eficácia, a maioria dos jogadores apresentou níveis intermediários de desempenho, com resultados semelhantes quando consideradas os diferentes escalões e géneros. Conclui-se que, por se tratar de escalões de formação, as componentes táticas poderão ser aperfeiçoadas a partir das vivências com a modalidade, melhorando a qualidade e a velocidade na tomada de decisão, fatores que influenciam diretamente a eficácia do jogador.

Epidemiology of diphtheria in the southwestern Indian Ocean is poorly documented. We analyzed 14 cases of infection with toxigenic Corynebacterium diphtheriae reported during 2007–2015 in Mayotte, a French department located in this region. Local control of diphtheria is needed to minimize the risk for importation of the bacterium into disease-free areas.

O objetivo deste estudo é avaliar qual modelo de atenção, entre unidade básica de saúde (UBS) tradicional e aquelas com Estratégia Saúde da Família (ESF), é mais orientado à atenção primária à saúde (APS) da criança, considerando a presença e a extensão dos atributos essenciais e derivados da APS. Foram entrevistados 1.484 familiares e ou cuidadores de crianças menores de 10 anos de idade cadastradas em unidades de saúde da família de João Pessoa na Paraíba, Brasil, e UBS tradicionais de Cascavel, e UBS mistas de Londrina, ambas no Paraná, Brasil. Para tanto, utilizou-se o Primary Care Assessment Tool Brasil, versão criança. Para análise utilizou-se o teste ANOVA one way paramétrica, para identificação de diferença estatisticamente significante entre os modelos de atenção, seguida do teste de comparação múltipla (post hoc) de Tukey, para apontar qual modelo apresentava diferença. Apesar de limitações no desenho do estudo, os achados levantam a hipótese de que a UBS mista é o modelo mais orientado à APS no cuidado à criança. Isso pode estar relacionado ao fato de que os diferentes modelos avaliados pertenciam a municípios diferentes, sem possibilidade de ajustar, na análise, as variáveis ligadas aos diferentes contextos. Assim, estudos futuros, com desenhos mais robustos, e ampliando para outros usuários e profissionais de saúde, poderão comprovar esta hipótese.

Guidelines for thyroid function evaluation recommend testing TSH first, then assessing fT4 only if TSH is out of the reference range (two-step), but many clinicians initially request both TSH and fT4 (one-step). Given limitations of previous studies, we aimed to compare the two-step with the one-step approach in an unselected community-dwelling study population, and develop a prediction score based on clinical parameters that could identify at-risk patients for thyroid dysfunction.Cross-sectional analysis of the population-based Busselton Health Study.We compared the two-step with the one-step approach, focusing on cases that would be missed by the two-step approach, i.e. those with normal TSH, but out-of-range fT4. We used likelihood ratio tests to identify demographic and clinical parameters associated with thyroid dysfunction and developed a clinical prediction score by using a beta-coefficient based scoring method.Following the two-step approach, 93.0% of all 4471 participants had normal TSH and would not need further testing. The two-step approach would have missed 3.8% of all participants (169 of 4471) with a normal TSH, but a fT4 outside the reference range. In 85% (144 of 169) of these cases, fT4 fell within 2 pmol/l of fT4 reference range limits, consistent with healthy outliers. The clinical prediction score that performed best excluded only 22.5% of participants from TSH testing.The two-step approach may avoid measuring fT4 in as many as 93% of individuals with a very small risk of missing thyroid dysfunction. Our findings do not support the simultaneous initial measurement of both TSH and fT4.

The most accessible points of call for most African populations with respect to primary health care are traditional health systems that include spiritual, religious, and herbal medicine. This review focusses only on the use of herbal medicines. Most African people accept herbal medicines as generally safe with no serious adverse effects. However, the overlap between conventional medicine and herbal medicine is a reality among countries in health systems transition. Patients often simultaneously seek treatment from both conventional and traditional health systems for the same condition. Commonly encountered conditions/diseases include malaria, HIV/AIDS, hypertension, tuberculosis, and bleeding disorders. It is therefore imperative to understand the modes of interaction between different drugs from conventional and traditional health care systems when used in treatment combinations. Both conventional and traditional drug entities are metabolized by the same enzyme systems in the human body, resulting in both pharmacokinetics and pharmacodynamics interactions, whose properties remain unknown/unquantified. Thus, it is important that profiles of interaction between different herbal and conventional medicines be evaluated. This review evaluates herbal and conventional drugs in a few African countries and their potential interaction at the pharmacogenomics level.

cuantitativo descriptivo que objetivó describir algunos aspectos de la atención prenatal de adolescentes en hospitales de enseñanza de la región Sur y Nordeste de Brasil, basado en los criterios de calidad del Programa de Humanización del Prenatal. Es un recorte de la “pesquisa “Redes sociales de apoyo a la paternidad en la adolescencia”. La colecta de los datos ocurrió de diciembre de 2008 a diciembre de 2009. La amuestra se constituyó de 559 puérperas adolescentes. Los resultados evidenciaron que 98% de las pesquisadas realizaron prenatal, 67,2% frecuentaron seis o más consultas médicas y 62,5% empezaron en el primer trimestre de gestación. Cuanto a los análisis de rutina, ni todos fueron realizados y 41,8% negaron haber recibido informaciones acerca del trabajo de parto y parto durante las consultas prenatales. Se concluye que la mayoría de las adolescentes realizó el prenatal conforme los criterios preconizados por el Programa, pero todavía hacen falta acciones educativas y orientaciones durante las consultas.