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In the field of architecture, codesign has been explored through various methodologies and tools, with the latter still in their nascent stages regarding their ability to effectively communicate with users, potentially leading to less inclusive processes. In this context, the use of full-scale models emerges as an alternative codesign tool due to its capacity to provide information, engage users, and encourage mutual learning. This research delves into this topic, contrasting full-scale models with two traditional participatory tools, namely architectural visualisations and small-scale models. Two design processes were experimented with, applying action research as a methodology with a primarily qualitative focus. Through maps, photographic documentation, and surveys, the interactions experienced by users with the three tools were graphically represented. This information was then compared using an evaluation table, which demonstrated the advantages of each tool that mitigate their respective limitations. For example, architectural visualisations excel in rapid information transmission, small-scale models offer flexibility, and full-scale models enhance inclusivity. This table can serve as a guide for planning other codesign processes. [ABSTRACT FROM AUTHOR]

Introduction: Sexuality influences thoughts, feelings, actions and interactions and therefore also affects our physical and mental health. It is a complex part of life, shaped by many factors, including religious ones. Religiosity can guide the sexual and loving experience, directly influencing the individual's sexual understanding, such as the use or not of condoms during sexual practice. Therefore, the present study aims to identify in the literature the influence of religion on female sexuality. Methodology: A narrative review of the literature was carried out in the PubMed database. Articles published in English, Spanish, Portuguese and Arabic from January 2017 to December 2022 were included, such as: clinical trials, meta-analysis and systematic review, which exclusively addressed female sexuality and religion. Studies that addressed male sexuality were excluded. Results: 74 articles were found, of which 28 were selected for reading according to the summary and 10 studies met the inclusion criteria and were analyzed. Most of the studies were on the Muslim, Islamic and Christian religions. Important points related to religious beliefs were identified, such as non-use of contraceptive methods, lack of knowledge about reproductive health, religious conflicts, marital status, virginity, sexual submission and menstrual taboos that negatively influence the quality of sexual life of religious women.. Studies with greater methodological rigor are needed to address this important issue. Conclusion: This review showed that religion can have an adverse impact on the sexual health and quality of life of Islamic, Christian and Muslim women. Highlighting the need to conduct research in this area to understand and address this relationship. Financing: No conflict. [ABSTRACT FROM AUTHOR]

Introduction: There are several aspects that involve the sexual function of an individual, such as biological, psychological and interpersonal factors. Based on this, symptoms of female sexual dysfunction are classified according to the response phase of the affected sexual cycle. In physiotherapy there are some resources that are used for the treatment of sexual dysfunctions, including vibration, which is used with the aim of improving muscle condition and vascularization, but the real effects of applying this technique in the treatment are not known. of sexual dysfunctions. Thus, the objective of this study was to identify evidence on the benefits of vibration in female sexual dysfunctions. Methodology: The PubMed and VHL databases were searched according to a search strategy defined by PICOS: ((((sexuality) OR (sexual dysfunction)) OR (pelvic floor disorders)) OR (women's health)) AND (vibration), which included systematic reviews, meta-analyses and clinical trials from 2012 to 2022 that approached vibration as a resource investigated or used in female sexual dysfunctions. Other study designs were excluded, as well as those that did not use vibration as a resource or that were aimed solely at the male audience. Results: A total of 89 articles were found, of which 83 were excluded for not meeting the inclusion criteria; six articles were selected to compose this review. Among the selected articles, three brought vibration as a purely evaluative resource, and three articles also looked for evidence on the use of vibration as a treatment for female sexual dysfunctions. Conclusion: No studies were found in which vibration has been used as a therapeutic resource in female sexual dysfunctions, which opens precedents for future studies in this regard. Financing: No conflict. [ABSTRACT FROM AUTHOR]

Introduction: Erectile dysfunction, premature ejaculation, retrograde ejaculation, delayed ejaculation, anejaculation, painful ejaculation, anorgasmia, hematospermia and low sexual desire are the main male sexual dysfunctions. The 2022 European Association of Urology recommends the use of vibratory stimulation and vacuum erection devices in the treatment of male sexual dysfunctions (mainly anejaculation and erectile dysfunction), both as adjuvant therapy and as combination therapy with other interventions. The objective of the study was to verify if there is scientific evidence for the use of vibrating stimulation and the vacuum erection device in male sexual dysfunctions that allow clinical indication in an effective and safe manner. Methods: Literature review by searching for scientific articles in the Pubmed database of the National Library of Medicine published in the last 10 years, including randomized clinical trials, meta-analysis studies, pilot studies, systematic literature reviews and guidelines. Results: As a result 1,230 articles on male sexual dysfunction. After screening, 16 studies were selected that are part of this research, seven articles on vibratory stimulation and nine on vacuum erection devices. Conclusion: This review suggests that vacuum erection and vibratory stimulation devices, as they offer low risk, minimal side effects, are accessible and cost-effective compared to other approaches, are promising devices for the non-invasive treatment of male dysfunctions. sex. Other studies with greater methodological rigor are needed. Descriptors: Vibratory stimulation; sexual dysfunction; penis vibrator; male sexual dysfunction; vacuum erectile; vacuum erection; Peyronie's disease Financing: No conflict. [ABSTRACT FROM AUTHOR]

Time-resolved small angle X-ray measurements are used to investigate the dynamic response to nonlinear oscillatory stresses and strains of a nematic dispersion of colloidal gibbsite platelets. We track the full 3D rotational motion of the director by employing plate-plate and concentric cylinder Couette geometries as well as a vertical X-ray beam. Under nonlinear oscillatory stress, we observe strong offsets in the rheological response as well as asymmetrical behavior in the microscopic structural response. This offset and asymmetry are connected to the yielding behavior of the platelets. By increasing the stress amplitude, we observed that the offset of the rheological response diminishes and the microscopic response becomes more symmetric; however, this strongly depends on the frequency of the stress input, and hence the time necessary for the system to yield. [ABSTRACT FROM AUTHOR]

Evasion of cell death is fundamental to the development of cancer and its metastasis. The role of the BCL-2-mediated (intrinsic) apoptotic program in these processes remains poorly understood. Here we have investigated the relevance of the pro-apoptotic protein BIM to breast cancer progression using the MMTV-Polyoma middle-T (PyMT) transgenic model. BIM deficiency in PyMT females did not affect primary tumor growth, but substantially increased the survival of metastatic cells within the lung. These data reveal a role for BIM in the suppression of breast cancer metastasis. Intriguingly, we observed a striking correlation between the expression of BIM and the epithelial to mesenchymal transition transcription factor SNAI2 at the proliferative edge of the tumors. Overexpression and knockdown studies confirmed that these two genes were coordinately expressed, and chromatin immunoprecipitation analysis further revealed that Bim is a target of SNAI2. Taken together, our findings suggest that SNAI2-driven BIM-induced apoptosis may temper metastasis by governing the survival of disseminating breast tumor cells. [ABSTRACT FROM AUTHOR]

Background Tranexamic acid ( TXA) reduces blood transfusion in surgery but the extent of the reduction in blood loss and how it relates to the dose of TXA is unclear. Methods A systematic review of randomized trials was performed. Data were extracted on blood loss from trials comparing intravenous TXA with no TXA or placebo in surgical patients. A Bayesian linear regression was used to describe the relationship between the reduction in blood loss with TXA and the extent of bleeding as measured by the mean blood loss in the control group. A meta-analysis of the log-transformed data was conducted to quantify the effect of TXA on blood loss, stratified by type of surgery, timing of TXA administration and trial quality. Meta-regression was used to explore the effect of TXA dosage. Results Data from 104 trials were examined. Although the absolute reduction in blood loss with TXA increased as surgical bleeding increased, the percentage reduction was similar. TXA reduced blood loss by 34 per cent (pooled ratio 0·66, 95 per cent confidence interval 0·65 to 0·67; P < 0·001). The percentage reduction in blood loss with TXA differed by type of surgery, timing of TXA administration and trial quality, but the differences were small. The effect of TXA on blood loss did not vary over the range of doses assessed (5·5-300 mg/kg). Conclusion TXA reduces blood loss in surgical patients by about one-third. A total dose of 1 g appears to be sufficient for most adults. There is no evidence to support the use of high doses. [ABSTRACT FROM AUTHOR]

A number of risk scores already exist to predict cardiovascular (CV) events. However, scores developed with data collected some time ago might not accurately predict the CV risk of contemporary hypertensive patients that benefit from more modern treatments and management. Using data from the randomised clinical trial Anglo-Scandinavian Cardiac Outcomes Trial-BPLA, with 15 955 hypertensive patients without previous CV disease receiving contemporary preventive CV management, we developed a new risk score predicting the 5-year risk of a first CV event (CV death, myocardial infarction or stroke). Cox proportional hazard models were used to develop a risk equation from baseline predictors. The final risk model (ASCORE) included age, sex, smoking, diabetes, previous blood pressure (BP) treatment, systolic BP, total cholesterol, high-density lipoprotein-cholesterol, fasting glucose and creatinine baseline variables. A simplified model (ASCORE-S) excluding laboratory variables was also derived. Both models showed very good internal validity. User-friendly integer score tables are reported for both models. Applying the latest Framingham risk score to our data significantly overpredicted the observed 5-year risk of the composite CV outcome. We conclude that risk scores derived using older databases (such as Framingham) may overestimate the CV risk of patients receiving current BP treatments; therefore, 'updated' risk scores are needed for current patients. [ABSTRACT FROM AUTHOR]

Abstract: The electrospinning of urethane based low molecular weight polymers differing only in the nature of the hydrogen bonding end-groups has been investigated. For the end-groups with the lowest binding constants at maximum solubility only droplets, are produced at the electrode; in contrast, increasing the binding constant of the end-group results in electrospun fibres being produced. The properties of the fibres produced are subject to changes in solvent, concentration and temperature. Typical diameters for these fibres were found to be some 10s of μm, rather than the sub-micron dimensions often produced in electrospinning systems. Such diameters are related to the high initial concentrations required; this also may influence the rate of solvent removal and preferential surface solidification which feature in these examples. A simple theoretical model is used to relate the association constant to the molecular weight required for fibre formation; significantly lower levels of association are required for higher molecular weight macromonomers compared to smaller molecular systems. [Copyright &y& Elsevier]

The pro-apoptotic BH3-only protein Bim has a major role in hematopoietic homeostasis, particularly in the lymphocyte compartment, where it strongly affects immune function. The three major Bim isoforms (BimEL, BimL and BimS) are generated by alternative splicing. BimEL, the most abundant isoform, contains a unique sequence that has been reported to be the target of phosphorylation by several MAP kinases. In particular, Erk1/2 has been shown to interact with BimEL through the DEF2 domain of BimEL and specifically phosphorylate this isoform, thereby targeting it for ubiquitination and proteasomal degradation. To examine the physiological importance of this mechanism of regulation and of the alternative splicing of Bim, we have generated several Bim knock-in mouse strains and analyzed their hematopoietic system. Although mutation in the DEF2 domain reduces BimEL degradation in some circumstances, this mutation did not significantly increase Bim's pro-apoptotic activity in vivo nor impact on the homeostasis of the hematopoietic system. We also show that BimEL and BimL are interchangeable, and that BimS is dispensable for the function of Bim. Hence, we conclude that physiological regulation of Bim relies on mechanisms independent of its alternative splicing or the Erk-dependent phosphorylation of BimEL. [ABSTRACT FROM AUTHOR]

Background: The detection of adverse events following immunization (AEFI) fundamentally depends on how these events are classified. Standard methods impose a choice between either grouping similar events together to gain power or splitting them into more specific definitions. We demonstrate a method of medically guided Bayesian information sharing that avoids grouping or splitting the data, and we further combine this with the standard epidemiological tools of stratification and multivariate regression.Objective: The aim of this study was to assess the ability of a Bayesian hierarchical model to identify gastrointestinal AEFI in children, and then combine this with testing for effect modification and adjustments for confounding.Study Design: Reporting odds ratios were calculated for each gastrointestinal AEFI and vaccine combination. After testing for effect modification, these were then re-estimated using multivariable logistic regression adjusting for age, sex, year and country of report. A medically guided hierarchy of AEFI terms was then derived to allow information sharing in a Bayesian model.Setting: All spontaneous reports of AEFI in children under 18 years of age in the WHO VigiBase™ (Uppsala Monitoring Centre, Uppsala, Sweden) before June 2010. Reports with missing age were included in the main analysis in a separate category and excluded in a subsequent sensitivity analysis.Exposures: The 15 most commonly prescribed childhood vaccinations, excluding influenza vaccines.Main Outcome Measures: All gastrointestinal AEFI coded by WHO Adverse Reaction Terminology.Results: A crude analysis identified 132 signals from 655 reported combinations of gastrointestinal AEFI. Adjusting for confounding by age, sex, year of report and country of report, where appropriate, reduced the number of signals identified to 88. The addition of a Bayesian hierarchical model identified four further signals and removed three. Effect modification by age and sex was identified for six vaccines for the outcomes of vomiting, nausea, diarrhoea and salivary gland enlargement.Conclusion: This study demonstrated a sequence of methods for routinely analysing spontaneous report databases that was easily understandable and reproducible. The combination of classical and Bayesian methods in this study help to focus the limited resources for hypothesis testing studies towards adverse events with the strongest support from the data. [ABSTRACT FROM AUTHOR]

Aims To evaluate, in hypertensive patients, whether the metabolic syndrome is a better predictor of new-onset diabetes compared with impaired fasting glucose, obesity or its other individual components alone, or collectively. Methods Cox models were developed to assess the risk of new-onset diabetes associated with the metabolic syndrome after adjusting for a priori confounders (age, sex, ethnicity and concomitant use of non-cardiovascular medications), its individual components and other determinants of new-onset diabetes. Area under receiver operator curves using the metabolic syndrome or models of impaired fasting glucose were compared, and the ability of these models to correctly identify those who (after 5-years of follow-up) would or would not develop diabetes was assessed. Results The metabolic syndrome adjusted for a priori confounders and its individual components, and further adjusted for other determinants, was associated with significantly increased risk of new-onset diabetes [1.19 (1.00-1.40), P = 0.05 and 1.22 (1.03-1.44), P = 0.02, respectively]. The discriminative ability of the metabolic syndrome model [area under receiver operating curve: 0.764 (0.750-0.778)] was significantly better than the model of impaired fasting glucose [0.742 (0.727-0.757)] (P < 0.001). The metabolic syndrome correctly allocates the risk of new-onset diabetes in a significantly higher proportion of patients (62.3%) than impaired fasting glucose status (37.7%) (P < 0.001). The presence of both the metabolic syndrome and impaired fasting glucose were associated with an approximately 9-fold (7.47-10.45) increased risk of new-onset diabetes. Among normoglycaemic patients, the metabolic syndrome was also associated with significantly increased risk of new-onset diabetes, after adjusting for BMI and a priori confounders [1.66 (1.29-2.13)]. Conclusions Both impaired fasting glucose and the metabolic syndrome predict the risk of new-onset diabetes; however, the metabolic syndrome is a better predictor than impaired fasting glucose in assigning the risk of new-onset diabetes in hypertensive patients, and among those with normoglycaemia. [ABSTRACT FROM AUTHOR]

Introduction Along with death engraftment, in recent years, antibody-mediated damage has been identified as the leading cause of loss of kidney transplants. Despite the recognition of the role of the B-lymphocyte subpopulation in the development of both tolerance and rejection, little is known about the trigger mechanisms and effectors of this humoral response. Background We analyzed the relationship between B lymphocyte subpopulations and levels of B-cell–activating factor (BAFF) with the histological findings in biopsies of renal transplantation. Material and Methods We selected 35 patients whose kidney transplant biopsy was performed between January and November 2015. The biopsy specimens were classified according to Banff criteria. At the moment of the biopsy BAFF levels and B-lymphocyte subpopulations in blood were measured using enzyme-linked immunosorbent assay (ELISA) and using flow cytometry, respectively. Results Mean BAFF levels were 493 ± 245 pg/mL. The median performance of biopsy post-transplantation was 12.9 (11.7-23.9) months. BAFF levels correlated with pretransplantation antibodies ( r = 0.523; P = .002) but not with kidney function. In biopsies performed more than 1 year after transplantation BAFF levels correlated with the severity of chronic glomerular (cg) involvement ( r = 0.625; P = .003). Histological variables related to antibody-mediated injury selected by principal component analysis (glomerulitis, peritubular capillary, and chronic glomerulopathy) related to BAFF levels (B factor, 116; 95% confidence interval [CI], 12–220; P = .029). Biopsy specimens with transplant glomerulopathy (TG) showed lower levels of circulating naive CD19 + subpopulation, IgD+, and CD27- (32.7 ± 28.1 vs 87.9 ± 79.1; P = .017) compared with biopsy specimens without TG. Conclusions Elevated levels of BAFF are associated with increased presence and severity of TG and a set of variables related to antibody-mediated histological damage. TG is associated with changes in circulating B-lymphocyte subpopulations that could contribute to its pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: White adipose tissue (WAT) is a major source of production of cytokines involved in chronic diseases such as obesity, type 2 diabetes, and atherosclerosis. Long-term exercise has been proposed as a therapy to reduce chronic inflammation. We investigated here the influence of an intense exercise training (over 7 weeks) on several cytokine concentrations including interleukin 1 receptor antagonist (IL-1ra), IL-1β, and IL-12 in serum, WAT, and skeletal muscle (SM) from non-obese rats. Two groups of 10 rats were investigated: one group was progressively trained (the two last weeks: 120min per day, 25m/min, 7% grade, 5 days per week) and the other age-matched group was used as a sedentary control. Compared to sedentary rats, weight gain was lower in the trained rats (P <0.01). In WAT, concentrations of IL-1ra, IL-1β, and IL-12 were lower (P <0.001 for IL-1ra and IL-12, P <0.05 for IL-1β) while they were higher in SM (P <0.01 for IL-1ra, P <0.001 for IL-1β, P <0.05 for IL-12), and similar in serum. Significant correlations were noted between (i) body weight and WAT concentrations of IL-1ra, IL-1β, and IL-12 (0.595, 0.450, and 0.481, respectively), (ii) body weight and IL-1β concentration in SM (−0.526). We also observed significant negative correlations between WAT and SM concentrations of the three cytokines. We show here for the first time that intense exercise training with weight loss reduced concentrations of IL-1ra, IL-1β, and IL-12 in WAT, while it increased them in SM. These results suggest that exercise could help reduce inflammation in WAT through mobilization of immune cells producing pro- and anti-inflammatory cytokines in SM. [Copyright &y& Elsevier]

This investigation examined the impact of a multistressor situation on salivary immunoglobulin A (sIgA) levels, and incidence of upper respiratory tract infection (URTI) during the French commando training (3 weeks of training followed by a 5-day combat course). For the URTI, the types of symptoms were classified according to the anatomical location of the infection. Saliva samples were collected (8 a.m.) from 21 males [21 (2) years] before entry into the commando training, the morning following the 3 weeks of training, after the 5-day combat course, and after 1 week of recovery. sIgA, protein and cortisol concentrations were measured. Symptoms of URTI were recorded during the study from health logs and medical examinations. After the 3 weeks of training, the sIgA concentration was not changed, although it was reduced after the 5-day course [from 120 (14) mg l(-1) to 71 (9) mg l(-1), P<0.01]. It returned to pre-training levels within a week of recovery. The incidence of URTI increased during the trial (chi(2)=53.48; P<0.01), but was not related to sIgA. Among the 30 episodes of URTI reported, there were 12 rhino-pharyngitis, 6 bronchitis, 5 tonsillitis, 4 sinusitis and 3 otitis. Cortisol levels were raised after the 3-week training (P<0.01), dropping below baseline after the combat course (P<0.01). Stressful situations have an adverse effect on mucosal immunity and incidence of URTI. However, the relationship between sIgA and illness remained unclear. The large proportion of rhino-pharyngitis indicated that the nasopharyngeal cavity is at a higher risk of infection. [ABSTRACT FROM AUTHOR]

Aims. – To examine the different components of fatigue.Current knowledge. – Numerous works have shown that enhanced physical load could result in fatigue which is characterised by a decrease in physical and mental performance. Fatigue is caused by an energy imbalance between nutritional intake and energy expenditure due to muscular work. Supplementary chronobiological and psychological stress facilitates fatigue. The general effect of these different factors is responsible for hormonal and immune changes.Points of view and plans. – The main hormonal axes, which respond to fatigue, are the gonadal and somatotrope axes, the hypothalamo–pituitary–adrenal axis, the medullo-sympathetic axis, and the neurotransmitters. The metabolic and hormonal changes during fatigue are responsible of important modifications, both of some central neurotransmitters and of some immune functions. Several data underline that increases and decreases in serotonergic activity during prolonged exercise hasten and delay fatigue. It has been also shown that there is a functional link between the hormonal response and the immune status decrease, which is under influence of muscle inflammation because of exercise excess. [Copyright &y& Elsevier]

Aims. – To examine the effects of physical exercise on leptin levels.Current knowledge. – Leptin plays a key role in the regulation of energy balance. Leptin acts as a satiety factor informing the central nervous system of changes in the amount of adipose tissue in the body and plays a role in the lipid metabolism. Exercise may contribute to the regulation of circulating leptin levels and leptin action. It would be a threshold in energy expenditure to reach during acute exercise (~800 kcal) to reduce leptin levels. A short or long-term training (< or > to 12 weeks) will not modify basal leptin levels without changes in body composition (body fat reduction). Caloric restriction is necessary during training to modify leptin levels.Points of views and plans. – Physiological mechanisms are now proposed to explain exercise-induced changes in leptin levels. Exercise-induced reduction in insulin levels and elevation in circulating catecholamines could be considered as mediators of leptin response. Determination of changes in leptin levels during exercise could represent an important indicator of nutritional status, body composition, and reproductive disorders. It would be of interest during the overtraining syndrome. [Copyright &y& Elsevier]

This study was designed to determine whether the immune and hormonal systems were affected by a 5-day military course following 3 weeks of combat training in a population of 26 male soldiers (mean age, 21 +/- 2 years). The combination of continuous heavy physical activity and sleep deprivation led to energy deficiency. At the beginning of the training program and immediately after the combat course, saliva samples were assayed for secretory immunoglobulin A and plasma samples were assayed for interleukin-6, dehydroepiandrosterone sulfate, prolactin, catecholamines, glucocorticoids, and testosterone. Secretory immunoglobulin A was lower and circulating interleukin-6 was increased by the end of the course, which was attributed to sympathoadrenergic stimulation. Dehydroepiandrosterone sulfate, prolactin, and testosterone levels fell significantly. These results suggest that prolonged and repeated exercise such as that encountered in a military training program induces immune impairment via a decrease in mucosal immunity and a release of interleukin-6 into the circulation. The impaired secretion of dehydroepiandrosterone sulfate and prolactin, two immunomodulatory hormones, was thought to be a response to the chronic stressors. Lowered testosterone reflects a general decrease in steroid synthesis as a consequence of the physical and psychological strain. [ABSTRACT FROM AUTHOR]

ABSTRACT The relationship between brain glucose and serotonin is still unclear and no direct evidence of an action of brain glucose on serotonergic metabolism in central fatigue phenomena has been shown yet. In order to determine whether or not brain glucose could influence the brain 5-hydroxytryptamine (5-HT) system, we have monitored in microdialysis the effects of a direct injection of glucose in rat brain hippocampus on serotonergic metabolism [i.e. 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan (TRP)], during high intensive treadmill running. The injection was performed just before and after exercise. We have shown that glucose induced a decrease of brain 5-HT levels to a minimum of 73.0 ± 3.5% of baseline after the first injection (P < 0.01) and to 68.5 ± 5.5% of baseline after the second injection (P < 0.01) and consequently prevented the exercise-induced 5-HT enhanced levels. We have observed the same phenomenon concerning the 5-HIAA, but brain TRP levels were not decreased by the injections. In conclusion, this study demonstrates that brain glucose can act on serotonergic metabolism and thus can prevent exercise-induced increase of 5-HT levels. The results also suggest that extracellular brain glucose does not act on the synthesis way of 5-HT, but probably on the release/reuptake system. [ABSTRACT FROM AUTHOR]

ABSTRACT The influence of the two distinct training programmes, moderate (M) and intensive (I), on hypothalamo–pituitary–adrenal (HPA) axis was investigated, in rats. Changes in plasma concentrations of adrenocorticotropin hormone (ACTH) and corticosterone were followed in response to (i) a 60-min acute running session performed on 2nd, 4th and 6th of the seven training weeks (ii) an acute restraint stress of 40 min applied after the final training programme. After 2nd, 4th and 6th week of the two training programmes, a 60-min running resulted in an enhanced secretion of ACTH and corticosterone, compared with both the baseline values (i.e. before running) and to the sedentary (S) group. However, on 4th and 6th weeks compared with 2nd week, ACTH and corticosterone remained elevated in intensive group when they are significantly reduced in moderate group. We could suggest that a moderate training resulted in an adapted hormonal response whereas a deadapted process occurred for the intensive programme. The day after the last training session, basal ACTH, corticosterone and corticosteroid-binding globulin (CBG) capacity were not affected by training. Hypothalamic corticotropin-releasing factor tissue-content (CRF) was increased significantly in the two trained groups. When compared with the sedentary group, the body weight of the rats in the two trained groups was significantly decreased with a total adrenal mass increasing but only in intensive group. The surimposed restraint stress resulted in significant increases in plasma ACTH and corticosterone both in trained and in sedentary animals. This result suggests that the adapted HPA axis response induced by both a moderate and intensive training do not prevent against the effects of a novel stress such as restraint stress. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess extracellular glucose changes in hippocampus in response to physical exercise and to determine the influence of glucose supplementation. In the same time, we have observed the changes in serotonin, in order to study the relationship between glucose and serotonin during exercise. Both glucose and serotonin were assessed using microdialysis. Exercise induced an increase in extracellular glucose levels over baseline during exercise to 121.1 ± 3.0% (P < 0.001), then a decrease to baseline during recovery. The serotonin followed glucose changes during the first 90 min of exercise, but followed a different pattern during recovery, increasing to a maximum of 129.9 ± 7.0% after 30 min of recovery (P < 0.001). When a 15% glucose solution was infused (10 μL min–1) during exercise and recovery, blood glucose concentration was increased, but extracellular brain glucose decreased to reach a minimum of 73.3 ± 4.6% after 90 min of recovery (P < 0.001). Serotonin was always the mirror-reflect of cerebral glucose, with a maximum increase of 142.0 ± 6.9% after 90 min of recovery (P < 0.001). These results show that exercise induces changes in brain glucose and 5-hydroxytryptamine (5-HT) levels, which were dramatically modified by glucose infusion. Taking into account the implication of brain 5-HT in central fatigue, they suggest that if glucose supplementation, before and during exercise, undoubtedly increase performance because of its peripheral positive action, it would have a negative impact on the quality of recovery after the end of the exercise. [ABSTRACT FROM AUTHOR]

[Display omitted] Soft, waterborne polyurethane dispersions are indispensable components in many state-of-the-art materials, with applications ranging from binders for coatings and adhesives to matrixes for flexible devices. While the static bulk nanostructure of such systems is widely studied, the influence that environmental conditions such as relative humidity and airflow have on their film formation and phase segregation behavior in supported films is unknown. Here, we elucidate the nanostructure evolution occurring during drying of an industrially relevant, soft polyurethane, utilizing real-time, non-destructive grazing incidence X-ray scattering analysis. Using an environmental-controlled casting cell, we highlight the differences between the drying mechanism under different conditions generated by tuning the airflow and the relative humidity. Our results show how the environment's relative humidity strongly influences chain aggregation and chain interdiffusion due to extended plasticization of the hard segment at high humidities, while accelerated air flows are responsible for the occurrence of (partial) skinning. Interestingly, despite changes in the chain aggregation behavior and occurrence of skinning and skin breakup during drying resulting in higher roughness at the film surface, minor influence is registered on the bulk tensile properties of the films, revealing the resilient nature towards environmental conditions of these soft weakly phase segregating polyurethane systems. [ABSTRACT FROM AUTHOR]

Magnetic form factors corresponding to elastic electron scattering from odd- A nuclei are presented. The calculations are carried out in plane-wave Born approximation. The one-body properties are obtained in a deformed self-consistent mean-field calculation based on a Skyrme HF+BCS method. Collective effects are also included in the cranking approximation. Results on several stable nuclei are compared with the available experimental information. It is shown that a deformed formalism improves the agreement with experiment in deformed nuclei, while reproducing equally well spherical nuclei by taking properly the spherical limit of the deformed model and the effect of nucleon-nucleon correlations. Thus, the capability of the model to describe magnetic form factors is demonstrated. This opens the door to explore also unstable nuclei of particular interest that could be measured in future experiments on electron-radioactive beam colliders. [ABSTRACT FROM AUTHOR]

Introduction: Sexual dysfunction is an alteration in one or more components of the sexual response cycle and dyspareunia is the dysfunction in which the woman experiences pain before, during or after vaginal penetration, which impairs quality of life and relationship with the couple. Physiotherapy uses several techniques to address this dysfunction, including pelvic floor muscle training (PFMT) and perineal massage (PM), but studies on the actual effects of these techniques and the resolution of dyspareunia are still scarce. Therefore, the objective of this study is to identify the evidence on the use of PFMT and MP techniques in the treatment of women with dyspareunia. Materials/Methods: Research carried out in the PEDro, Pubmed and MEDLINE databases. Articles of the type were included: clinical trials, meta-analysis and systematic reviews, published in English and Portuguese; in the period from 2013 to 2023; who addressed TMAP and MP techniques in the treatment of dyspareunia. Those who did not meet the inclusion criteria were excluded. Results: In total, 525 articles were identified, but only 9 studies were selected for this review as they met the inclusion criteria. Most of the results showed significant responses to treatment with the use of PFMT and MP, and even the studies in which they did not obtain significance did not rule out the possibility of these techniques, since they do not present side effects and have good potential. to improve. Many studies have low methodological quality. Conclusion: It was observed in the literature that PFMT and MP have good responses in the treatment of dyspareunia, but there is not enough support in the literature to demonstrate their effectiveness. It is necessary to develop future studies with better methodological quality for more solid scientific evidence. Financing: No conflict. [ABSTRACT FROM AUTHOR]

Purpose: TGF-β1 and 2 exert fibrogenic and hypertrophic effects in the myocardium under biomechanical stress. Another member of the TGF-β family, Bone Morphogenetic Protein 7 (BMP7), opposes TGF-β-induced fibrogenesis. Herein, we assessed the role of BMP7 in the LV remodeling response to pressure overload and in the LV reverse remodeling after pressure overload release.Methods: C57BL6 and BMP7+/- mice were subjected to 4 wk aortic arch banding (AB) or 4 wk banding followed by debanding surgery (DB). Echocardiography was performed using Vevo-770 equipment (VisualSonics). Histological fibrosis (Masson trichrome) and myocardial expression of fibrosis related genes (qPCR) were analyzed. Statistical analyses: ANOVA and Bonferroni test.Results: s.c. delivery (4 wk) of recombinant BMP7 (rBMP7) to AB mice diminished LV hypertrophy (LV mass, 4wk AB: 117.3±3.5 mg vs 4wk B+BMP7: 93.2±2.5 mg, p<0.001) and gene and histological fibrosis. Systolic [(LVEF, 4 wk AB: 39±1.5% vs 4wk AB+BMP7: 58±3.5%, p<0.001); (MAPSE, 4 wk AB: 0.42±0.02 mm vs 4wk AB+BMP7: 0.56±0.02 mm p<0.001)] and diastolic (E/E`, 4 wk AB: 41±1 vs 4wk AB+BMP7: 29±1, p<0.001) dysfunctions were lessened. Following debanding (DB), most of the reverse remodeling occurred over the first postoperative week. One week treatment with a neutralizing BMP7-Ab, starting at DB, hampered remodeling regression [LV mass (1 wk DB: 104±3.6 mg vs 1 wk DB+BMP7-Ab: 114±3.5 mg; p<0.05); fibrotic area (1 wk DB: 0.4±0.09 % vs 1 wk DB+BMP7-Ab: 2.4±0.7 %; p<0.01)] and the recovery of LV dysfunction [(LVEF, 1 wk DB: 51±1.4% vs 1wk DB+BMP7-Ab: 45±1.4%, p<0.05); (MAPSE, 1 wk DB: 0.61±0.02 mm vs 1wk DB+BMP7-Ab: 0.49±0.03 mm p<0.01); (E/E`, 1 wk DB: 28±1.4 vs 1wk DB+BMP7-Ab: 39±2.2, p<0.01)]. Similarly, the myocardium from mice deficient in BMP7 displayed a poorer remodeling regression [LV mass (1 wk DB: 104±3.6 mg vs 1 wk DB-BMP7+/-: 111±4 mg); fibrotic area (1 wk DB: 0.4±0.09 % vs 1 wk DB-BMP7+/-: 2.8±0.5 %; p<0.01)] and less functional recovery than WT mice [(LVEF, 1 wk DB: 51±1.4% vs 1wk DB-BMP7+/-: 44±1.4%, p<0.05); (MAPSE, 1 wk DB: 0.61±0.02 mm vs 1wk DB-BMP7+/-: 0.42±0.02 mm p<0.001); (E/E`, 1 wk DB: 28±1.4 vs 1wk DB-BMP7+/-: 40±1.6, p<0.001)].Conclusion: BMP7 attenuated the myocardial remodeling response to pressure overload and facilitated the reverse remodeling and functional recovery after releasing the aortic constriction. Strategies to modulate the activity of BMP7 signaling and its consequences on the LV remodeling regression may have putative therapeutic value after valve replacement in patients with aortic stenosis. Funding: ISCIII PI12/00999. [ABSTRACT FROM PUBLISHER]

Highlights: [•] A reduced-complexity kinetic model for the FTS over Co–Re/Al2O3 was formulated. [•] The model described well the catalyst performance for CO conversions below 50%. [•] Strong diffusional limitations develop at high space-times and CO conversions. [•] Isothermal plug-flow model is valid for microreactors at moderate CO conversion. [•] Transport effects may become an issue for the FTS in microstructured reactors. [ABSTRACT FROM AUTHOR]

In this work, we report the genetic basis of C7 deficiency in two different Spanish families. In family 1, by using exon-specific polymerase chain reaction and sequencing, a recently described mutation was found in homozygosity in the patient; a single base change in exon 15 (C2107T) leading to a stop codon that causes truncation of the C-terminal portion of C7 (Q681X). Patient’s father, mother and sister were heterozygous for this mutation. Interestingly, patient’s parents were not related. In family 2, a new single base mutation in exon 2 (G90A), leading to a stop codon that causes the premature truncation of C7 (W8X), was found in the patient, mother and sister 1. Additionally, patient 2, her father and sisters, displayed a missense mutation in exon 9 (G1135C) resulting in a change of aminoacid (G357R). Although sister 1 bore the same mutations in the C7 gene that patient 2, she remains asymptomatic. Because both mutations were found in the patient and her sister, we analyse other defence mechanisms such as FcγR polymorphisms as well as mannose-binding lectin alleles ( MBL2 gene) and MBL levels. Results showed that both siblings bore identical combinations of FcγR allotypes and different MBL2 alleles, exhibiting patient 2 a MBL-insufficient genotype. Normal MBL levels were found in patient 1 and in two previously studied C7-deficient siblings, suggesting the involvement of other mechanisms of immunity distinct of FcγR variants and the MBL pathway, for the absence of meningococcal recurrent infections in certain C7-deficient individuals. [ABSTRACT FROM AUTHOR]

This study examined the effect of a probiotics supplementation on respiratory tract infection (RTI) and immune and hormonal changes during the French Commando training (3-week training followed by a 5-day combat course). Cadets (21 +/- 0.4 years) received either a probiotics (n = 24) or a placebo (n = 23) supplementation over the training period. We found no difference in the RTI incidence between groups but a significantly greater proportion of rhinopharyngitis in the probiotic group (p < 0.05). Among immune parameters, the major finding was an immunoglobulin A decrease after the combat course only in the placebo group (p < 0.01), but the difference between the two groups was not significant. A greater increase in dehydroepiandrostane sulfate was observed in the probiotics group after the combat course (p < 0.05). This study suggested that the benefits of a probiotics supplementation in a multistressor environment relied mainly on its capacity to prevent the infection to spread throughout the respiratory tract. [ABSTRACT FROM AUTHOR]

Abstract: Serotonin (5-HT) is a neurotransmitter and an immune modulator. At the periphery, the serotonergic system appears to possess a regulatory activity via 5-HT1B receptors. The present study investigated the effects of a 5-day military course following 3 weeks of combat training on the functional activity of 5-HT1B/1D receptors in peripheral blood lymphocytes of male soldiers. The results of [35S]GTPγS binding assays showed that h5-HT1B/1D receptors were desensitized after the training program, although serum 5-HT was unchanged. These data suggest the existence of a control on T cells mediated through h5-HT1B/1D receptors leading cytokine production modulation after a physical training. [Copyright &y& Elsevier]

Abstract: Objectives. – This study assesses on patients with myophosphorylase deficiency (McArdle’s disease) the effects of a moderate aerobic training program (8 weeks, 3 sessions of 45 minutes per week at 60–70% of maximal heart rate) on the physiological response during exercise. Methods. – The cardiorespiratory, electromyographic (EMG) and metabolic responses are evaluated on four patients before and after training to an acute exercise (1 h) on an ergometric bicycle (20–35 Watts) followed by 30 minutes recovery. Results. – Before training, the EMG activity is very high during the first ten minutes of exercise while oxygen uptake (VO2) remains stable over the 60 minutes of exercise. The heart rate (FC) and the rate of perceived exertion (RPE) are markedly increased. Patients highly use circulatory glucose and free fatty acids for oxidation. During exercise, the 8-week training program reduces EMG activity, FC, RPE and the time of second-wind apparition whereas it has any effect on VO2. At the end of exercise recovery, patients use more circulatory glucose and product lactate; moreover, their respiratory exchange ratio is increased. Conclusion. - Patients with McArdle disease show an exacerbation of cardiorespiratory, electromyographic and metabolic responses to exercise. A moderate aerobic training program induces muscle, cardiac and metabolic adaptations to physical strain and improves the tolerance of the patients to the physical exercise. [Copyright &y& Elsevier]

Dispersions of colloidal platelets in the nematic phase display strong wall anchoring, which competes with the reorientational motion of the director when the system is subjected to flow. We show that the mechanical response to large amplitude oscillatory strain and stress depends on the confinement of the system due to this competition. We elucidate the underlying structural response by deflecting a x-ray beam vertically along the vorticity direction of a Couette geometry, such that the structure can be probed throughout the gap with an unprecedented spatial resolution while recording in situ the mechanical response. We observe strong inhomogeneities in terms of the orientation of the nematic director, depending on the extent of the system's yield during an oscillation. At small strain amplitudes, we observe a small region where the director oscillates between wall anchoring and the Leslie angle, while in the bulk, the director tilts out of the flow–flow gradient plane. At large strain amplitudes, the oscillations of the director are symmetric, close to the wall, and propagate into the bulk. Here, a twinning is observed where the director rotates out-of-plane in two opposite directions. Using the sequence of physical process method to analyze the LAOStrain response for both the mechanical and structural response, we locate the yielding in a small time-window around flow reversal and identify that the bulk is the main contributor to the mechanical response. The structural response to LAOStress is much less pronounced even when the stress amplitude causes significant shear thinning. [ABSTRACT FROM AUTHOR]

The brain serotonin (5-HT) system and circulating corticosteroids are in close interaction and both implicated in the pathogenesis of affective disorders. We evaluated the effects of adrenalectomy (ADX) on 5-HT1B receptors mRNA expression in cerebellum, frontal cortex, striatum and hippocampus in rats, using the RNase protection assay technique. Eight weeks after bilateral adrenalectomy, 5-HT1B receptor mRNA levels were decreased in the cerebellum and in the frontal cortex. The expression of 5-HT1B receptors mRNA was unchanged in the hippocampus and in the striatum. This data indicates regional differences in the effects of long term adrenalectomy on the expression of 5-HT1B receptors. [Copyright &y& Elsevier]

Background: Liver stiffness (LS) at sustained viral response (SVR) is strongly associated with a lower incidence of subsequent hepatic events. HIV NNRTIs may have a beneficial impact on fibrogenesis.Objectives: Our aim was to analyse the influence of NNRTI-based therapy on the change in LS from starting direct-acting antiviral (DAA) therapy to achieving SVR in HIV/HCV-coinfected patients.Methods: Three hundred and thirteen HIV/HCV-coinfected patients who fulfilled the following criteria were included: (i) had achieved SVR with an IFN-free, DAA-including regimen; (ii) LS ≥9.5 kPa before therapy; (iii) LS measurement available at SVR; (iv) seronegative for HBsAg; and (v) ART containing 2 NRTIs plus either 1 NNRTI or 1 integrase inhibitor (INI) or 1-2 NRTIs plus 1 PI. LS changes were assessed.Results: Seventy-four patients received NNRTI-based combinations [53 (71.6%) rilpivirine and 16 (21.6%) efavirenz] and 239 patients received other regimens. At baseline, the median (IQR) LS was 16.7 kPa (11.8-25.6) in the NNRTI group and 17.3 kPa (11.9-27.4) in the non-NNRTI group (P = 0.278). The median (IQR) percentage of LS decrease from baseline to SVR was 35.2% (18.2%-52.3%) for NNRTI-based therapy and 29.5% (10%-45.9%) for PI- or INI-based therapy (P = 0.018). In multivariate analysis, adjusted for sex, age, HCV genotype, NRTI backbone and propensity score for HIV therapy, NNRTI-based regimen use was associated with a higher LS decrease [β = 11.088 (95% CI = 1.67-20.51); P = 0.021].Conclusions: Treatment with NNRTI plus 2 NRTI combinations is associated with a higher LS decline than other ART combinations in HIV/HCV-coinfected patients receiving DAA-based therapy. [ABSTRACT FROM AUTHOR]

Background Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). Methods In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication—hepatic decompensation or hepatocellular carcinoma (HCC)—or requiring liver transplant after SVR. Results During a median (Q1–Q3) follow-up of 31.6 (22.7–36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28–9.12]), pretreatment CPT class B or C (62.5 [3.08–1246.42]) and MELD scores (1.37 [1.03–1.82]), CPT class B or C at SVR (10.71 [1.32–87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49–13.15]), FIB-4 index at SVR (1.39 [1.13–1.70]), and LS at SVR (1.05 [1.02–1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. Conclusions LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs. [ABSTRACT FROM AUTHOR]

Summary: Background: A long‐term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. Objectives: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate‐to‐severe atopic eczema, to assess the long‐term safety risk of these therapies in a routine clinical care setting. Methods: We describe a registry‐embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. Conclusions: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long‐term data on the safety of systemic immunomodulating therapies in patients with atopic eczema.Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long‐term safety profile against established therapies.Large numbers of patients with a long duration of follow‐up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries.We present a protocol for an investigator‐initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate‐to‐severe atopic eczema.This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations. Plain language summary available online [ABSTRACT FROM AUTHOR]

• Emulsifier and dispersed phase compositions are optimized to obtain stable PCMEs. • Suspended droplets remain nanometric through storage time and thermal cycling. • Optimized PCM emulsions exhibit reduced subcooling degrees (∼3 °C). • Slurries show Newtonian viscosities when dispersed droplets are liquid. • The stored energy by PCMEs is up to 18–31% larger than that of water. Phase change material emulsions (PCME) have gained increasing scientific interest due to their potential to enhance the storage capability of thermal facilities. Herein we present the design and characterization of oil−in−water (O/W) nanoemulsions by employing a dispersed phase mixture (2–12 wt%) enriched in methyl myristate as phase change material. The emulsifier and dispersed phase compositions were optimized based on dynamic light scattering and calorimetric analyses. A two−surfactant formulation composed of sodium dodecyl sulfate and BrijTM S2 (20:49 in weight) was selected to produce stable colloidal dispersions of a methyl stearate: n –hexadecane:methyl myristate mixture (at a mass proportion of 1:3:36) in water. No phase separation or significant growth in emulsified droplet size was detected under storage conditions or when the slurries were subjected to different heating−cooling cycles. The melting/crystallization transitions, rheological behavior, thermal conductivity and density of optimized nanoemulsions were experimentally investigated in order to further understand how the concentration and physical state of suspended droplets may influence those thermal and physical properties. According to differential scanning calorimetry studies, slurries showed moderate subcooling degrees (∼3 °C), even though their solid−liquid transitions extended over a slightly wider range of temperatures than the same mixture used as the dispersed phase but in bulk−form. The shear−thinning character observed for developed nanoemulsions at low temperatures disappeared with the melting of suspended droplets. Considering an operating temperature interval of 15 °C around melting−crystallization phase changes, the 12 wt% optimized suspension presented a storage capacity 18 % higher than that of water under the same conditions. Furthermore, thermal reliability tests verified that phase change characteristics did not significantly changed after 8 months of storage and throughout 500 thermal cycles. [ABSTRACT FROM AUTHOR]

• Supramolecular polyurethanes with varied loadings of a low molecular weight bis-urea additive. • LMWAs cooperatively self-assemble with supramolecular polyurethanes. • LMWAs enhance the properties of the addressable and healable polymer networks. Low molecular weight additives which can cooperatively self-assemble with supramolecular polyurethanes via complementary hydrogen bonding interactions offer an attractive route to enhancing the properties of addressable polymer networks. Here, we present the design, synthesis, characterisation and mechanical properties of a series of supramolecular polyurethanes with varied loadings of a low molecular weight bis-urea additive. These additives are able to self-assemble with analogous recognition motifs within the supramolecular polyurethanes to form polar 'hard' domains, promoting phase separation within the material and, crucially, increasing the strength of the polymer network. In addition, the bis-urea additive is a by-product within the polymerisation and thus can be synthesised in situ , without the need for complex purification or blending. The mechanical properties of these reinforced polymers were enhanced when compared to the pristine supramolecular polyurethane alone, as a result of higher degrees of order within the polymer matrix. Furthermore, a formulation comprising the small molecule blended with the supramolecular polyurethane was produced to examine the effect of material preparation and filler dispersion within the polymer matrix. Interestingly, the mechanical performance of a blended material was diminished as a result of modest dispersion and incorporation within the polymer matrix. These findings thus demonstrate a facile, one-pot, method that does not require purification to produce reinforced supramolecular polyurethanes. This methodology may find use in industrial applications in which enhancements to the physical and mechanical properties can be easily achieved through the in situ synthesis of low molecular weight additives within the polymerisation. [ABSTRACT FROM AUTHOR]

Objectives: Our objective was to identify patient factors associated with being untreated for hepatitis C virus (HCV) infection in HIV‐coinfected patients. Methods: A prospective longitudinal study was carried out. HIV‐infected patients with active chronic HCV infection included in the HERACLES cohort (NCT02511496) constituted the study population. The main study outcome was receipt of HCV direct‐acting antiviral (DAA) treatment from 1 May 2015 to 1 May 2017. The population was divided into patients who were receiving HCV treatment during follow‐up and those who were not. Results: Of the 15 556 HIV‐infected patients in care, 3075 (19.7%) presented with chronic HCV infection and constituted the study population. At the end of the follow‐up, 1957 patients initiated HCV therapy (63.6%). Age < 50 years, absence of or minimal liver fibrosis, being treatment‐naïve, HCV genotype 3 infection, being in the category of people who inject drugs using opioid substitutive therapy (OST‐PWID), and being in the category of recent PWID were identified as significant independent risk factors associated with low odds of DAA implementation. When a multivariate analysis was performed including only the PWID population, both OST‐PWID [odds ratio (OR) 0.552; 95% confidence interval (CI) 0.409–0.746) and recent PWID (OR 0.019; 95% CI 0.004–0.087) were identified as independent factors associated with low odds of treatment implementation. Conclusions: We identified factors, which did not include prioritization of a DAA uptake strategy, that limited access to HCV therapy. The low treatment uptake in several populations seriously jeopardizes the elimination of HCV infection in the coming years. [ABSTRACT FROM AUTHOR]

Little data are available on renal toxicity exerted by direct-acting antivirals (DAAs) in real life. The aim of this study was to assess the impact of direct-acting antivirals against hepatitis C virus infection currently used in Spain and Portugal on the estimated glomerular filtration rate (eGFR) in clinical practise. From an international, prospective multicohort study, patients treated with DAAs for at least 12 weeks and with eGFR ≥30 mL/min per 1.73 m2 at baseline were selected. eGFR was determined using the CKD-EPI formula. A total of 1131 patients were included; 658 (58%) were HIV/HCV-coinfected patients. Among the 901 patients treated for 12 weeks, median (interquartile range) eGFR was 100 (87-107) at baseline vs 97 (85-105) mL/min per 1.73 m2 at week 12 of follow-up (FU12) post-treatment (P < .001). For HIV-coinfected subjects who received tenofovir plus a ritonavir-boosted HIV protease inhibitor (PI/r), baseline vs FU12 eGFR were 104 (86-109) vs 104 (91-110) mL/min per 1.73 m2 (P = .913). Among subjects receiving ombitasvir/paritaprevir with or without dasabuvir, eGFR did not show any significant change. Of 1100 subjects with eGFR >60 mL/min per 1.73 m2 at baseline, 22 (2%) had eGFR <60 mL/min per 1.73 m2 at FU12, but none presented with eGFR <30 mL/min per 1.73 m2. In conclusion, eGFR slightly declines during therapy with all-oral DAAs and this effect persists up to 12 weeks after stopping treatment in subjects with normal to moderately impaired renal function, regardless of HIV status. Concomitant use of tenofovir plus PI/r does not seem to have an impact on eGFR. [ABSTRACT FROM AUTHOR]

Objectives Fatty liver disease ( FLD) is frequently observed in HIV-infected patients. Obesity and type 2 diabetes mellitus (T2 DM) are strongly associated with FLD. Because genetic variants within the fat mass and obesity-associated ( FTO) gene have been associated with both pathologies, our aim was to evaluate the association of single nucleotide polymorphisms ( SNPs) within the FTO, previously related to obesity or T2 DM, with FLD in HIV-infected patients. Methods FLD was defined as a value of the controlled attenuation parameter ( CAP) ≥ 238 dB/m, obtained by transient elastography. Four SNPs within FTO intron 1 (rs11642841, rs8050136, rs9939609 and rs9940128) were genotyped in 421 individuals using a custom Golden Gate protocol. The results were replicated in a validation sample consisting of a further 206 HIV-infected patients. Multivariate logistic regression analyses were conducted in the entire population. Results Three SNPs (rs8050136, rs9939609 and rs9940128) were associated with FLD, with rs9940128 showing the strongest association. This polymorphism also showed an association with FLD in the validation sample. In total, rs9940128 was genotyped in 627 HIV-infected patients, including 267 (42.6%) FLD-diagnosed individuals. The frequency of FLD among rs9940128 AA carriers was 55.7% (63 of 113 individuals) and that in patients without this genotype was 39.7% (204 of 514 individuals) [ P = 0.009; adjusted odds ratio 1.88; 95% confidence interval ( CI) 1.17-3.01]. Conclusions Variations within FTO may be predictors of FLD in HIV-infected patients independently of metabolic factors. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to evaluate the impact of liver stiffness (LS) on the response to direct-acting antiviral (DAA)-based therapy against hepatitis C virus (HCV) infection in cirrhotic patients. Those patients included in two Spanish prospective cohorts of patients receiving therapy based on at least one DAA, who showed a baseline LS ≥ 12.5 kPa and who had reached the scheduled time point for sustained virological response evaluation 12 weeks after completing therapy (SVR12) were analysed. Pegylated interferon/ribavirin-based therapy plus an HCV NS3/4A protease inhibitor (PR-PI group) was administered to 198 subjects, while 146 received interferon-free regimens (IFN-free group). The numbers of patients with SVR12 according to an LS < 21 kPa versus ≥21 kPa were 59/99 (59.6%) versus 46/99 (46.5%) in the PR-PI group ( p = 0.064) and 41/43 (95.3%) versus 90/103 (87.4%) in the IFN-free group ( p = 0.232). Corresponding figures for the relapse rates in those who presented end-of-treatment response (ETR) were 3/62 (4.8%) versus 10/56 (17.9%, p = 0.024) and 1/42 (2.4%) versus 8/98 (8.2%, p = 0.278), respectively. In a multivariate analysis adjusted for age, sex and use of interferon, a baseline LS ≥ 21 kPa was identified as an independent predictor of relapse [adjusted odds ratio, AOR (95% confidence interval, CI): 4.228 (1.344-13.306); p = 0.014] in those patients with ETR. LS above 21 kPa is associated with higher rates of relapse to DAA-based therapy in HCV-infected patients with cirrhosis in clinical practice. LS could help us to tailor the duration and composition of DAA-based combinations in cirrhotic subjects, in order to minimise the likelihood of relapse. [ABSTRACT FROM AUTHOR]

In April 2015, the Spanish National Health System (SNHS) developed a national strategic plan for the diagnosis, treatment, and management of hepatitis C virus (HCV). Our aim was to analyze the impact of this on human immunodeficiency virus (HIV)-infected patients included in the HERACLES cohort during the first 6 months of its implementation. The HERACLES cohort (NCT02511496) was set up in March 2015 to evaluate the status and follow-up of chronic HCV infection in patients co-infected with HIV in the south of Spain. In September 2015, the data were analyzed to identify clinical events (death, liver decompensation, and liver fibrosis progression) and rate of treatment implementation in this population. The study population comprised a total of 3474 HIV/HCV co-infected patients. The distribution according to liver fibrosis stage was: 1152 F0-F1 (33.2 %); 513 F2 (14.4 %); 641 F3 (18.2 %); 761 F4 (21.9 %); and 407 whose liver fibrosis was not measured (12.3 %). During follow-up, 248 patients progressed by at least one fibrosis stage [7.1 %; 95 % confidence interval (CI): 6.3-8 %]. Among cirrhotic patients, 52 (6.8 %; 95 % CI: 5.2-8.9 %) developed hepatic decompensation. In the overall population, 50 patients died (1.4 %; 95 % CI: 1.1-1.9 %). Eight hundred and nineteen patients (23.56 %) initiated interferon (IFN)-free treatment during follow-up, of which 47.8 % were cirrhotic. In our study, during 6 months of follow-up, 23.56 % of HIV/HCV co-infected patients included in our cohort received HCV treatment. However, we observed a high incidence of negative short-term outcomes in our population. [ABSTRACT FROM AUTHOR]

Total sleep deprivation (TSD) in humans is associated with altered hormonal levels, which may have clinical relevance. Less is known about the effect of an extended sleep period before TSD on these hormonal changes. Fourteen subjects participated in two experimental counterbalanced conditions (randomised cross-over design): extended sleep (21.00–07.00 h time in bed, EXT) and habitual sleep (22.30–07.00 h time in bed, HAB). For each condition, subjects performed two consecutive phases: six nights of either EXT or HAB. These nights were followed by 3 days in the sleep laboratory with blood sampling at 07.00 and 17.00 h at baseline (B-07.00 and B-17.00), after 24 and 34 h of continuous awakening (24 h-CA, 34 h-CA) and after one night of recovery sleep (R-07.00 and R-17.00) to assess testosterone, cortisol, prolactin and catecholamines concentrations. At 24 h of awakening, testosterone, cortisol and prolactin concentrations were significantly lower compared to B-07.00 and recovered basal levels after recovery sleep at R-07.00 (P < 0.001 for all). However, no change was observed at 34 h of awakening compared to B-17.00. No effect of sleep extension was observed on testosterone, cortisol and catecholamines concentrations at 24 and 34 h of awakening. However, prolactin concentration was significantly lower in EXT at B-07.00 and R-07.00 compared to HAB (P < 0.05, P < 0.001, respectively). In conclusion, 24 h of awakening inhibited gonadal and adrenal responses in healthy young subjects and this was not observed at 34 h of awakening. Six nights of sleep extension is not sufficient to limit decreased concentrations of testosterone and cortisol at 24 h of awakening but may have an impact on prolactin concentration. [ABSTRACT FROM AUTHOR]

The implementation of hepatitis C (HCV) direct-acting antiviral drugs is prioritized in several populations in which its application provides the most immediate and impactful benefit. In this scenario, a precise knowledge of the situation of human immunodeficiency virus (HIV)/HCV chronic co-infection is required to adequately address this disease. This cross-sectional study was performed in 21 hospitals in Andalusia (Spain). The study population consisted of HIV-infected patients with an active HCV chronic infection who were not receiving HCV treatment at the time of inclusion. A total of 13,506 HIV-infected patients were included in the study. Of them, 2561 (18.9 %) presented chronic HCV infection. The majority of the patients included were on highly active antiretroviral therapy (HAART; 96.2 %), showed plasma levels with an undetectable HIV viral load (92.5 %), and had a good immunological status (median CD4+ cell count of 486 cells/mL). The HCV genotype distribution was as follows: 58.1 % were genotype 1, 1.1 % were genotype 2, 16.1 % were genotype 3, and 22.1 % were genotype 4 (2.6 % were missing data). In total, 24.8 % of the patients showed liver fibrosis stage F0-F1, 27.9 % showed stage F2, 16.7 % showed stage F3, and 21 % showed stage F4 (9.6 % were missing data). With regards to previous HCV treatment experiences, 68.05 % of the patients were naïve and 31.95 % had failed to respond to a previous treatment. The burden of HCV/HIV co-infected patients in our population was reported as one in five HIV-infected patients requiring HCV treatment. The implementation of extra resources to face this important health challenge is mandatory. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the efficacy of and the risk of major bleeding during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients according to the pretreatment platelet count. Two hundred and seventy-four HCV/HIV-coinfected, previously naïve individuals with compensated cirrhosis enrolled in one Spanish prospective cohort who received peg-IFN/RBV were included in this study. The frequency of severe bleeding and sustained virological response (SVR) rate were compared between patients with a pretreatment platelet count ≤70,000/mm and >70,000/mm, respectively. Sixty-one (22 %) patients had a baseline platelet count ≤70,000/mm. The median (Q1-Q3) pretreatment platelet count was 58,000 (49,000-65,000) cells/mm in the platelet ≤70,000 group and 129,000 (102,500-166,000) cells/mm in the platelet >70,000 group ( p < 0.0001). Seventeen (28 %) subjects of the platelet ≤70,000 group and 71 (33 %) patients of the platelet >70,000 group achieved SVR ( p = 0.4). Only 2 (3.2 %) patients in the platelet ≤70,000 group developed a severe hemorrhagic event, specifically esophageal variceal bleeding. The efficacy of therapy with peg-IFN/RBV in HIV/HCV-coinfected patients with low pretreatment platelet counts is comparable to that found in the overall subset of subjects with compensated cirrhosis. The frequency of severe hemorrhagic events related with this therapy is low in this population. [ABSTRACT FROM AUTHOR]

Structure formation during flow, a common phenomenon driving polymer processing, can have a major effect on the rheological behavior of a polymer melt. This can cause large increases of the pressure and thus large changes in thermodynamical properties which, in turn, will strongly influence the structure formation. Consequently, a complex, mutual, self-influencing process, occurring at rather short times, arises. This process is investigated with combined in situ small-angle X-ray scattering and wide-angle X-ray diffraction at high acquisition frequency (30 Hz) in a piston driven slit flow device using linear low density polyethylene as a model material. A decrease of crystallinity is observed immediately after flow and related to an unusual melting of part of the oriented crystals. The experimental observation is explained in terms of pressure dependency of the undercooling. The undercooling first increases during flow because of the pressure rise and then drops when pressure relaxes to equilibrium values; as a consequence, the critical stable lamellar thickness is not constant in time, although the experiments are conducted in isothermal conditions. A mechanism is proposed and validated using a structural model to fit SAXS data: the increase of undercooling during flow promotes nucleation of gradually thinner lamellae on the pre-existing kebab nucleated from shish cores that relax back to the melt state after depressurization. Our results show that in modeling real-life processes involving combination of flow and high pressures, like injection molding, the effect of pressure on the shear layer formation cannot be neglected. [ABSTRACT FROM AUTHOR]