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BackgroundThe physical and cognitive demands of combat flying may influence the development and persistence of flight-related neck pain (FRNP). The aim of this pilot study was to analyse the effect of a multimodal physiotherapy program which combined supervised exercise with laser-guided feedback and interferential current therapy on psychophysiological variables in fighter pilots with FRNP.MethodsThirty-one fighter pilots were randomly assigned to two groups (Intervention Group: n = 14; Control Group: n = 17). The intervention consisted of 8 treatment sessions (twice per week) delivered over 4 weeks. The following primary outcomes were assessed: perceived pain intensity (Numeric Pain Rating Scale-NPRS) and Heart Rate Variability (HRV; time-domain, frequency-domain and non-linear variables). A number of secondary outcomes were also assessed: myoelectric activity of the upper trapezius and sternocleidomastoid, pain catastrophizing (Pain Catastrophizing Scale-PCS) and kinesiophobia (TSK-11).ResultsStatistically significant differences (p≤0.05) within and between groups were observed for all outcomes except for frequency domain and non-linear HRV variables. A significant time*group effect (one-way ANOVA) in favour of the intervention group was found for all variables (pConclusionsThe use of a multimodal physiotherapy program consisting of supervised exercise with laser-guided feedback and interferential current appears to show clinical benefit in fighter pilots with FRNP.Trial registrationClinicalTrials.gov: NCT05541848.

BackgroundEffective nutrition management is fundamental in the comprehensive treatment of individuals with type 2 diabetes. Various strategies have been explored in this regard, demonstrating their potential usefulness in improving clinical outcomes. This systematic review aims to assess the impact of meals frequency on the well-being of these patients.Methods and findingsIn accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar databases were searched until July 10th, 2023. We included studies from the last 10 years in people with type 2 diabetes that had an intervention regarding their meal frequency. The risk of bias was evaluated based on the Cochrane tool according to the type of study. Of 77 retrieval articles, 13 studies matched our inclusion criteria. The primary focus of each study was to evaluate glycemic control as the major outcome. Studies suggest that meal frequency, time-restricted feeding, breakfast skipping, bedtime snacking, and chrononutrition practices all play roles in type 2 diabetes management and risk.ConclusionsRestricting feeding to 2 to 3 meals per day and practicing time restricted feeding with less than 10 hours of daily food intake promotes weight loss and glycemic control in patients with type 2 diabetes. Aligning food consumption with the body's natural rhythm is beneficial, whereas skipping breakfast disrupts this rhythm. Snacking after evening or waiting 3-4 hours after meal helps control glucose levels, but consuming pre-bedtime snacks do not provide the same benefits.Prospero registration numberCRD42023431785.

Background: The physical and cognitive demands of combat flying may influence the development and persistence of flight-related neck pain (FRNP). The aim of this pilot study was to analyse the effect of a multimodal physiotherapy program which combined supervised exercise with laser-guided feedback and interferential current therapy on psychophysiological variables in fighter pilots with FRNP. Methods: Thirty-one fighter pilots were randomly assigned to two groups (Intervention Group: n = 14; Control Group: n = 17). The intervention consisted of 8 treatment sessions (twice per week) delivered over 4 weeks. The following primary outcomes were assessed: perceived pain intensity (Numeric Pain Rating Scale–NPRS) and Heart Rate Variability (HRV; time-domain, frequency-domain and non-linear variables). A number of secondary outcomes were also assessed: myoelectric activity of the upper trapezius and sternocleidomastoid, pain catastrophizing (Pain Catastrophizing Scale–PCS) and kinesiophobia (TSK-11). Results: Statistically significant differences (p≤0.05) within and between groups were observed for all outcomes except for frequency domain and non-linear HRV variables. A significant time*group effect (one-way ANOVA) in favour of the intervention group was found for all variables (p<0.001). Effect sizes were large (d≥0.6). Conclusions: The use of a multimodal physiotherapy program consisting of supervised exercise with laser-guided feedback and interferential current appears to show clinical benefit in fighter pilots with FRNP. Trial registration: ClinicalTrials.gov: NCT05541848. [ABSTRACT FROM AUTHOR]

Aldehyde dehydrogenases (ALDHs) is a protein superfamily that catalyzes the oxidation of aldehyde molecules into their corresponding non-toxic carboxylic acids, and responding to different environmental stresses, offering promising genetic approaches for improving plant adaptation. The aim of the current study is the functional analysis for systematic identification of S. lycopersicum ALDH gene superfamily. We performed genome-based ALDH genes identification and functional classification, phylogenetic relationship, structure and catalytic domains analysis, and microarray based gene expression. Twenty nine unique tomato ALDH sequences encoding 11 ALDH families were identified, including a unique member of the family 19 ALDH. Phylogenetic analysis revealed 13 groups, with a conserved relationship among ALDH families. Functional structure analysis of ALDH2 showed a catalytic mechanism involving Cys-Glu couple. However, the analysis of ALDH3 showed no functional gene duplication or potential neo-functionalities. Gene expression analysis reveals that particular ALDH genes might respond to wounding stress increasing the expression as ALDH2B7. Overall, this study reveals the complexity of S. lycopersicum ALDH gene superfamily and offers new insights into the structure-functional features and evolution of ALDH gene families in vascular plants. The functional characterization of ALDHs is valuable and promoting molecular breeding in tomato for the improvement of stress tolerance and signaling.

BackgroundThe main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use.MethodsA retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL.Results135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic.ConclusionsIn a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.

The Cueva de Ardales is a hugely important Palaeolithic site in the south of the Iberian Peninsula owing to its rich inventory of rock art. From 2011–2018, excavations were carried out in the cave for the first time ever by a Spanish-German research team. The excavation focused on the entrance area of the cave, where the largest assemblage of non-figurative red paintings in the cave is found. A series of 50 AMS dates from the excavations prove a long, albeit discontinuous, occupation history spanning from the Middle Palaeolithic to the Neolithic. The dating of the Middle Palaeolithic layers agrees with the U/Th dating of some red non-figurative paintings in the entrance area. In addition, a large assemblage of ochre lumps was discovered in the Middle Palaeolithic layers. Human visits of the cave in the Gravettian and Solutrean can be recognized, but evidence from the Aurignacian and Magdalenian cannot be confirmed with certainty. The quantity and nature of materials found during the excavations indicate that Cueva de Ardales was not a campsite, but was mainly visited to carry out non-domestic tasks, such as the production of rock art or the burial of the dead.

Malignant pleural mesothelioma (MPM) is a cancer associated with asbestos exposure and its diagnosis is challenging due to the moderate sensitivities of the available methods. In this regard, miR-103a-3p was considered to increase the sensitivity of established biomarkers to detect MPM. Its behavior and diagnostic value in the Mexican population has not been previously evaluated. In 108 confirmed MPM cases and 218 controls, almost all formerly exposed to asbestos, we quantified miR-103-3a-3p levels in leukocytes using quantitative Real-Time PCR, together with mesothelin and calretinin measured in plasma by ELISA. Sensitivity and specificity of miR-103-3a-3p alone and in combination with mesothelin and calretinin were determined. Bivariate analysis was performed using Mann-Whitney U test and Spearman correlation. Non-conditional logistic regression models were used to calculate the area under curve (AUC), sensitivity, and specificity for the combination of biomarkers. Mesothelin and calretinin levels were higher among cases, remaining as well among males and participants ≤60 years old (only mesothelin). Significant differences for miR-103a-3p were observed between male cases and controls, whereas significant differences between cases and controls for mesothelin and calretinin were observed in men and women. At 95.5% specificity the individual sensitivity of miR-103a-3p was 4.4% in men, whereas the sensitivity of mesothelin and calretinin was 72.2% and 80.9%, respectively. Positive correlations for miR-103a-3p were observed with age, environmental asbestos exposure, years with diabetes mellitus, and glucose levels, while negative correlations were observed with years of occupational asbestos exposure, creatinine, erythrocytes, direct bilirubin, and leukocytes. The addition of miR-103a-3p to mesothelin and calretinin did not increase the diagnostic performance for MPM diagnosis. However, miR-103a-3p levels were correlated with several characteristics in the Mexican population.

BackgroundPeople in their fifties with HIV are considered older adults, but they appear not to be a homogeneous group.ObjectiveTo evaluate the differences among older adults with HIV according to their chronological age and the year of HIV diagnosis.MethodsCross-sectional study of the FUNCFRAIL cohort. Patients 50 or over with HIV were included and were stratified by both chronological age and the year of HIV diagnosis: before 1996 (long-term HIV survivors [LTHS]) and after 1996. We recorded sociodemographic data, HIV-related factors, comorbidities, frailty, physical function, other geriatric syndromes, and quality of life (QOL).ResultsWe evaluated 801 patients. Of these, 24.7% were women, 47.0% were LTHS, and 14.7% were 65 or over. Of the 65 or over patients, 73% were diagnosed after 1996. Higher rates of comorbidities among LTHS were found, being the more prevalent: COPD, history of cancer, osteoarthritis, depression, and other psychiatric disorders while the more prevalent among the 65 or over patients were: hypertension, diabetes, dyslipidemia, cancer, and osteoarthritis. LTHS showed a significantly worse QOL. There were no differences by the year of HIV diagnosis regarding frailty and functional impairment (SPPB ConclusionsA LTHS and a 65 or over person are both "older adults with HIV," but their characteristics and requirements differ markedly. It is mandatory to design specific approaches focused on the real needs of the different profiles.

BackgroundWorkplace violence in healthcare settings has long been studied in scientific literature, particularly in the nursing profession. Research has explored mostly user violence probably for its high prevalence and impact on health and job satisfaction. Yet this focus may overshadow another dangerous type of workplace violence: coworker violence. Exerted by co-workers with similar status, lateral violence differs from that yielded by a co-worker with a higher rank, known as vertical. This study aims to deepen the knowledge about lateral violence perceived by nurses and its interaction with other variables commonly associated with workplace violence in healthcare: burnout, job satisfaction, and self-perceived health.MethodA random block sampling was performed, prompting a total sample of 925 nursing professionals from 13 public hospitals located in the southeast of Spain. The sample distribution (mean and standard deviation) and the response percentages according to the study variables of the ad-hoc questionnaire were analyzed and classified with cluster analysis.ResultsThrough the cluster analysis, two subgroups were obtained: Cluster 1, composed of 779 participants, with low scores in the variables used for the classification, high levels of both extrinsic and intrinsic satisfaction, low levels of emotional exhaustion and cynicism, and low rates of somatization, anxiety, social dysfunction and depression; and Cluster 2, composed of 115 participants and characterized by moderate-high scores in the variables used for the classification, moderate extrinsic satisfaction, and low intrinsic satisfaction, high emotional exhaustion and cynicism and lower somatization, anxiety, social dysfunction, and depression scores. Excluded cases amounted to 31.ConclusionNursing professionals who experience lateral violence reveal a lower intrinsic satisfaction, feeling less self-accomplished in their job, and less positive work experience. Emotional exhaustion rises as a concerning progressive and long-term outcome of experiencing this type of violence.

PURPOSE:Uncertainty exists regarding the best way to communicate cardiovascular risk (CVR) to patients, and it is unclear whether the comprehension and perception of CVR varies according to the format used. The aim of the present work was to determine whether a strategy designed for communicating CVR information to patients with poorly controlled high blood pressure (HBP), but with no background of cardiovascular disease, was more effective than usual care in the control of blood pressure (BP) over the course of a year. METHODS:A pragmatic, two-arm, cluster-randomized controlled trial was performed. Consecutive patients aged 40-65 years, all diagnosed with HBP in the last 12 months, and all of whom showed poor control of their condition (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg), were recruited at 22 primary healthcare centres. Eleven centres were randomly assigned to the usual care arm, and 11 to the informative intervention arm (Educore arm). At the start of the study, the Educore arm subjects were shown the "low risk SCORE table", along with impacting images and information pamphlets encouraging the maintenance of good cardiovascular health. The main outcome variable measured was the control of HBP; the secondary outcome variables were SCORE table score, total plasma cholesterol concentration, use of tobacco, adherence to prescribed treatment, and quality of life. RESULTS:The study participants were 411 patients (185 in the Educore arm and 226 in the usual care arm). Multilevel logistic regression showed that, at 12 months, the Educore intervention achieved better control of HBP (OR = 1.57; 1.02 to 2.41). No statistically significant differences were seen between the two arms at 12 months with respect to the secondary outcomes. CONCLUSIONS:Compared to usual care, the Educore intervention was associated with better control of HBP after adjusting for age, baseline SBP and plasma cholesterol, at 12 months.

This work provides an in-depth computational performance study of the parallel finite-difference time-domain (FDTD) method. The parallelization is done at various levels including: shared- (OpenMP) and distributed- (MPI) memory paradigms and vectorization on three different architectures: Intel's Knights Landing, Skylake and ARM's Cavium ThunderX2. This study contributes to prove, in a systematic manner, the well-established claim within the Computational Electromagnetic community, that the main factor limiting FDTD performance, in realistic problems, is the memory bandwidth. Consequently a memory bandwidth threshold can be assessed depending on the problem size in order to attain optimal performance. Finally, the results of this study have been used to optimize the workload balancing of simulation of a bioelectromagnetic problem consisting in the exposure of a human model to a reverberation chamber-like environment.

Solar energy has become an important renewable energy source for reducing the use of fossil fuels and to mitigate global warming, for which solar collectors constitute a technology that is to be promoted. The use of nanofluids can increase the efficiency of solar into thermal energy conversion in solar collectors. Experimental values for the specific heat, thermal conductivity and viscosity of alumina/water nanofluids are needed to evaluate the influence of the solid content (from 0.25 to 5 v%) and the flow rate on the Reynolds, Nusselt and the heat transfer coefficient. In the laminar flow regime, thermal conductivity enhancement over specific heat decrement is key parameter, and a 2.34% increase in the heat transfer coefficient is theoretically obtained for 1 v% alumina nanofluid. To corroborate the results, experimental tests were run in a flat plate solar collector. A reduction in efficiency from 47% to 41.5% and a decrease in the heat removal factor were obtained using the nanofluid due to the formation of a nanoparticle deposition layer adding an addition thermal resistance to heat transfer. Nanofluids are recommended only if the nanoparticle concentration is high enough to enhance thermal conductivity, but no so high so as to avoid wall deposition.

OBJECTIVE:We investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts. METHODS:A case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count

The alkaliphilic bacterium Pseudomonas pseudoalcaligenes CECT5344 uses free cyanide and several metal-cyanide complexes as the sole nitrogen source and tolerates high concentrations of metals like copper, zinc and iron, which are present in the jewelry wastewaters. To understand deeply the regulatory mechanisms involved in the transcriptional regulation of cyanide-containing wastewaters detoxification by P. pseudoalcaligenes CECT5344, RNA-Seq has been performed from cells cultured with a cyanide-containing jewelry wastewater, sodium cyanide or ammonium chloride as the sole nitrogen source. Small RNAs (sRNAs) that may have potential regulatory functions under cyanotrophic conditions were identified. In total 20 sRNAs were identified to be differentially expressed when compared the jewelry residue versus ammonium as nitrogen source, 16 of which could be amplified successfully by RT-PCR. As predicted targets of these 16 sRNAs were several components of the nit1C gene cluster encoding the nitrilase NitC essential for cyanide assimilation, the cioAB gene cluster that codes for the cyanide-insensitive cytochrome bd-type terminal oxidase, the medium length-polyhydroxyalkanoates (ml-PHAs) gene cluster, and gene clusters related with a global nitrogen limitation response like those coding for glutamine synthase and urease. Other targets were non-clustered genes (or their products) involved in metal resistance and iron acquisition, such as metal extrusion systems and the ferric uptake regulatory (Fur) protein, and a GntR-like regulatory family member probably involved in the regulation of the cyanide assimilation process in the strain CECT5344. Induction of genes targeted by sRNAs in the jewelry residue was demonstrated by qRT-PCR.

It has long been thought that emotional intelligence (EI) involves skillful emotion regulation, but surprisingly little is known about the precise links between EI and emotion regulation. To address this gap in the literature, we examined the relation between EI-operationalised as an ability-and the use of two common emotion regulation strategies-cognitive reappraisal and expressive suppression. Seven hundred and twelve participants from a community sample in Spain were assessed on ability EI (using the MSCEIT) and emotion regulation (using the ERQ). Findings revealed that EI ability was positively associated with cognitive reappraisal and negatively associated with expressive suppression. These relationships were moderated by gender and age. The strength of the association between EI and cognitive reappraisal increased with age for men, while this strength decreased with age for women. Conversely, the strength of the association between EI and suppression decreased with age for men, but increased with age for women. These findings confirm the expectation that EI is associated with greater use of generally adaptive forms of emotion regulation (reappraisal), and lesser use of generally maladaptive forms of emotion regulation (suppression), although effect sizes were quite modest. Observed differences in the strength of associations between EI and emotion regulation may be the result of gender differences in the development of emotional skills along with cultural changes in emotional education and social norms.

OBJECTIVES:Sexualized intravenous drug use, also known as slamsex, seems to be increasing among HIV-positive men who have sex with men (MSM). Physical and psychopathological symptoms have previously been reported in this population, although research on the subject of slamsex is scarce. The objectives of our study were to describe the psychopathological background of a sample of HIV-positive MSM who engaged in slamsex during the previous year and to compare physical, psychopathological, and drug-related symptoms between these participants and those who engaged in non-injecting sexualized drug use. DESIGN AND METHODS:Participants (HIV-positive MSM) were recruited from the U-Sex study in 22 HIV clinics in Madrid during 2016-17. All participants completed an anonymous cross-sectional online survey on sexual behavior and recreational drug use. When participants met the inclusion criteria, physicians offered them the opportunity to participate and gave them a card with a unique code and a link to access the online survey. The present analysis is based on HIV-positive MSM who had engaged in slamsex and non-injecting sexualized drug use. RESULTS:The survey sample comprised 742 participants. Of all the participants who completed the survey, 216 (29.1%) had engaged in chemsex, and of these, 34 (15.7%) had engaged in slamsex. Participants who engaged in slamsex were more likely to have current psychopathology (depression, anxiety, and drug-related disorders) than participants who engaged in non-injecting sexualized drug use. In addition, participants who engaged in slamsex more frequently reported high-risk sexual behaviors and polydrug use and were more often diagnosed with sexually transmitted infections (STIs) and hepatitis C than those who did not inject drugs. Compared with participants who did not inject drugs, participants who engaged in slamsex experienced more severe drug-related symptoms (withdrawal and dependence), symptoms of severe intoxication (loss of consciousness), and severe psychopathological symptoms during or after slamsex (eg, paranoid thoughts and suicidal behaviors). CONCLUSION:Slamsex is closely associated with current psychiatric disorders and severe drug-related and psychiatric symptoms.

BackgroundDespite having influenza vaccination policies and programs, countries in the Americas underutilize seasonal influenza vaccine, in part because of insufficient evidence about severe influenza burden. We aimed to estimate the annual burden of influenza-associated respiratory hospitalizations in the Americas.MethodsThirty-five countries in the Americas with national influenza surveillance were invited to provide monthly laboratory data and hospital discharges for respiratory illness (International Classification of Diseases 10th edition J codes 0-99) during 2010-2015. In three age-strata (ResultsSixteen of 35 countries (46%) contributed primary data to the analyses, representing 79% of the America's population. The average pooled rate of influenza-associated respiratory hospitalization was 90/100,000 population (95% confidence interval 61-132) among children aged ConclusionsInfluenza-associated respiratory hospitalizations impose a heavy burden on health systems in the Americas. Countries in the Americas should use this information to justify investments in seasonal influenza vaccination-especially among young children and the elderly.

BACKGROUND:Thrombotic microangiopathy (TMA) is an important complication associated with several diseases that are rare and life-threatening. TMA is common to thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP is defined by a severe deficiency of ADAMTS13, and early treatment is associated with good prognosis. The diagnosis of HUS can be difficult due to the potential multiple etiologies, and the best treatment option in most cases is not well-established yet. The implementation of a multidisciplinary team (MDT) could decrease the time to diagnosis and treatment for HUS and may improve the outcomes of these patients. OBJECTIVE:To determine the impact of MDT on morbidity and mortality [death or chronic renal replacement therapy (CRRT) requirements], incidence and response time [(RT) defined as the period between hospital admission and the first day of direct therapy administration], length of stay at an intensive care unit (ICU-LOS) and total hospitalization (T-LOS) were also assessed. METHODS:We compared a pre-MDT implementation period (from January/2008 to May/2016) versus post-MDT period (from May/2016 to December/2016). The screening TMA diagnosis was made according the following criteria: hemolytic anemia, thrombocytopenia and acute renal damage and without ADAMTS13 deficiency. An online chat was implemented to provide instant medical information. RESULTS:Twenty-eight patients were included. The incidence changed from 2.3 cases/pre-MDT: (all cases: n = 18) to 10 cases/year post-MDT (all cases: n = 10). Two patients died in pre-MDT and post- MDT (11% versus 20%, P = 0.60). From pre-MDT, the number of patients who required CRRT by post-MDT decreased from 7 (39%) to 0, P = 0.03. Similarly, RT, ICU-LOS and T-LOS [median(p25-p75)] decreased from 10 (2-12) days to 0.5 (0-1.5) days, P = 0.04, from 16 (9-30) days to 10 (4-13) days, P = 0.01 and from 33 (22-53) days to 16 (12-32) days, P < 0.01, respectively. CONCLUSION:MDT implementation was associated with a greater number of patients who meet TMA criteria. A decrease in the RT and T-LOS periods were observed and associated with better outcomes in these patients.

Loneliness has social and health implications. The aim of this article is to evaluate the association of loneliness with all-cause mortality.Pubmed, PsycINFO, CINAHL and Scopus databases were searched through June 2016 for published articles that measured loneliness and mortality. The main characteristics and the effect size values of each article were extracted. Moreover, an evaluation of the quality of the articles included was also carried out. A meta-analysis was performed firstly with all the included articles and secondly separating by gender, using a random effects model.A total of 35 articles involving 77220 participants were included in the systematic review. Loneliness is a risk factor for all-cause mortality [pooled HR = 1.22, 95% CI = (1.10, 1.35), p < 0.001] for both genders together, and for women [pooled HR = 1.26, 95% CI = (1.07, 1.48); p = 0.005] and men [pooled HR = 1.44; 95% CI = (1.19, 1.76); p < 0.001] separately.Loneliness shows a harmful effect for all-cause mortality and this effect is slightly stronger in men than in women. Moreover, the impact of loneliness was independent from the quality evaluation of each article and the effect of depression.

T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection.96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31-60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored.Parameters significantly associated with CD4 depletion in cART-naïve group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035).Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.

evaluate whether manual lymphatic drainage (MLD) or active exercise (AE) is associated with shoulder range of motion (ROM), wound complication and changes in the lymphatic parameters after breast cancer (BC) surgery and whether these parameters have an association with lymphedema formation in the long run.Clinical trial with 106 women undergoing radical BC surgery, in the Women's Integrated Healthcare Center-University of Campinas. Women were matched for staging, age and body mass index and were allocated to performed AE or MLD, 2 weekly sessions during one month after surgery. The wound was evaluated 2 months after surgery. ROM, upper limb circumference measurement and upper limb lymphoscintigraphy were performed before surgery, and 2 and 30 months after surgery.The incidence of seroma, dehiscence and infection did not differ between groups. Both groups showed ROM deficit of flexion and abduction in the second month postoperative and partial recovery after 30 months. Cumulative incidence of lymphedema was 23.8% and did not differ between groups (p = 0.29). Concerning the lymphoscintigraphy parameters, there was a significant convergent trend between baseline degree uptake (p = 0.003) and velocity visualization of axillary lymph nodes (p = 0.001) with lymphedema formation. A reduced marker uptake before or after surgery predicted lymphedema formation in the long run (>2 years). None of the lymphoscintigraphy parameters were shown to be associated with the study group. Age ≤39 years was the factor with the greatest association with lymphedema (p = 0.009). In women with age ≤39 years, BMI >24Kg/m2 was significantly associated with lymphedema (p = 0.017). In women over 39 years old, women treated with MLD were at a significantly higher risk of developing lymphedema (p = 0.011).Lymphatic abnormalities precede lymphedema formation in BC patients. In younger women, obesity seems to be the major player in lymphedema development and, in older women, improving muscle strength through AE can prevent lymphedema. In essence, MLD is as safe and effective as AE in rehabilitation after breast cancer surgery.

BACKGROUND:In pregnant women, the use of Mycophenolic acid (MPA) is associated with teratogenicity. Recently, the European Medicines Agency (EMEA) and the Spanish Agency of Medicine and Sanitary Products (AEMPS) warned about the potential teratogenic effects of MPA. These adverse events may occur even in children from males on treatment with MPA. However, evidence of malformations in offsprings of male kidney transplanted patients (KT) exposed to MPA is limited. Thus, the present study aimed to evaluate the incidence of offspring malformations in children of renal transplanted males under MPA. MATERIALS AND METHODS:We conducted a retrospective study in which we evaluated the incidence of malformations in descendants from male recipients that were exposed or not to MPA before and at the time of conception. Two groups of patients were evaluated. Those exposed to MPA (MPA group, n = 20) and the non-MPA group (n = 13) that included patients that did not receive AZA (n = 5) and eight that did receive AZA (n = 8) at the time of conception. RESULTS:A total of forty-nine post-transplant conceptions were identified from 33 different renal transplanted males. MPA was used as the immunosuppressant in 28 of the conceptions. Males from the non-MPA group fathered the other 21 children. Median time from grafting to conception was 6.1 (IQR 2.4-11.1) years, and it was similar between groups. There were eight miscarriage episodes, 2 in the non-MPA group and 6 in the MPA group although differences were not reached. After that, all patients had children without problems. No malformations were detected in any of the 49 regardless whether they were exposed or not to MPA. CONCLUSIONS:No evidence of MPA-associated malformations was observed in descendants of kidney transplanted males on treatment with MPA. Further research is warranted to confirm our findings to properly advice transplanted males keen to procreate.

BACKGROUND:Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. DESIGN:Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. METHODS:We evaluated effectiveness (defined as maintenance of HIV-1-RNA

BACKGROUND:There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. PATIENTS AND METHODS:Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study. All patients were untreated for both infections. Several CD4 and CD8 T-cell subsets involved in HIV-pathogenesis were investigated. Non-parametric tests were used to establish differences between groups and associations between variables. Multivariate linear regression was used to ascertain the variables independently associated with CD4 counts. RESULTS:HIV-patients presented significant differences compared to healthy controls in most of the parameters analyzed. Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia. Compared to HIV group, HIV/HCV group presented significantly higher levels of exhaustion (Tim3+PD1- subset) in total CD8+ T-cells (p = 0.003), and higher levels of exhaustion in CD8+HLADR+CD38+ (p = 0.04), CD8+HLADR-CD38+ (p = 0.009) and CD8+HLADR-CD38- (p = 0.006) subsets of CD8+ T-cells. Interestingly these differences were maintained after adjusting by CD4 counts and HIV-viremia. CONCLUSIONS:We show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection. The relevance of this phenomenon on immunological and/or clinical HIV progression prompts HCV treatment to improve management of coinfected patients.

Biological treatments to degrade cyanide are a powerful technology for cyanide removal from industrial wastewaters. It has been previously demonstrated that the alkaliphilic bacterium Pseudomonas pseudoalcaligenes CECT5344 is able to use free cyanide and several metal-cyanide complexes as the sole nitrogen source. In this work, the strain CECT5344 has been used for detoxification of the different chemical forms of cyanide that are present in alkaline wastewaters from the jewelry industry. This liquid residue also contains large concentrations of metals like iron, copper and zinc, making this wastewater even more toxic. To elucidate the molecular mechanisms involved in the bioremediation process, a quantitative proteomic analysis by LC-MS/MS has been carried out in P. pseudoalcaligenes CECT5344 cells grown with the jewelry residue as sole nitrogen source. Different proteins related to cyanide and cyanate assimilation, as well as other proteins involved in transport and resistance to metals were induced by the cyanide-containing jewelry residue. GntR-like regulatory proteins were also induced by this industrial residue and mutational analysis revealed that GntR-like regulatory proteins may play a role in the regulation of cyanide assimilation in P. pseudoalcaligenes CECT5344. The strain CECT5344 has been used in a batch reactor to remove at pH 9 the different forms of cyanide present in industrial wastewaters from the jewelry industry (0.3 g/L, ca. 12 mM total cyanide, including both free cyanide and metal-cyanide complexes). This is the first report describing the biological removal at alkaline pH of such as elevated concentration of cyanide present in a heterogeneous mixture from an industrial source.

As climate change is expected to have a significant impact on species distributions, there is an urgent challenge to provide reliable information to guide conservation biodiversity policies. In addressing this challenge, we propose a remote sensing-based approach to forecast the future habitat quality for European badger, a species not abundant and at risk of local extinction in the arid environments of southeastern Spain, by incorporating environmental variables related with the ecosystem functioning and correlated with climate and land use. Using ensemble prediction methods, we designed global spatial distribution models for the distribution range of badger using presence-only data and climate variables. Then, we constructed regional models for an arid region in the southeast Spain using EVI (Enhanced Vegetation Index) derived variables and weighting the pseudo-absences with the global model projections applied to this region. Finally, we forecast the badger potential spatial distribution in the time period 2071-2099 based on IPCC scenarios incorporating the uncertainty derived from the predicted values of EVI-derived variables. By including remotely sensed descriptors of the temporal dynamics and spatial patterns of ecosystem functioning into spatial distribution models, results suggest that future forecast is less favorable for European badgers than not including them. In addition, change in spatial pattern of habitat suitability may become higher than when forecasts are based just on climate variables. Since the validity of future forecast only based on climate variables is currently questioned, conservation policies supported by such information could have a biased vision and overestimate or underestimate the potential changes in species distribution derived from climate change. The incorporation of ecosystem functional attributes derived from remote sensing in the modeling of future forecast may contribute to the improvement of the detection of ecological responses under climate change scenarios.

Despite the huge body of research on social support, literature has been primarily focused on its beneficial role for both physical and mental health. It is still unclear why people with mental and neurological disorders experience low levels of social support. The main objective of this study was to explore what are the strongest factors related to social support and how do they interact with each other in neuropsychiatric disorders. The study used cross-sectional data from 722 persons suffering from dementia, depression, epilepsy, migraine, multiple sclerosis, Parkinson's disease, schizophrenia, stroke, and substance use disorders. Multiple linear regressions showed that disability was the strongest factor for social support. Extraversion and agreeableness were significant personality variables, but when the interaction terms between personality traits and disability were included, disability remained the only significant variable. Moreover, level of disability mediated the relationship between personality (extraversion and agreeableness) and level of social support. Moderation analysis revealed that people that had mental disorders experienced lower levels of support when being highly disabled compared to people with neurological disorders. Unlike previous literature, focused on increasing social support as the origin of improving disability, this study suggested that interventions improving day-to-day functioning or maladaptive personality styles might also have an effect on the way people perceive social support. Future longitudinal research, however, is warranted to explore causality.

Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups' classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease.

Over the last decades, global changes have altered the structure and properties of natural and semi-natural mountain grasslands. Those changes have contributed to grassland loss mainly through colonization by woody species at low elevations, and increases in biomass and greenness at high elevations. Nevertheless, the interactions between agropastoral components; i.e., ecological (grassland, environmental, and geolocation properties), social, and economic components, and their effects on the grasslands are still poorly understood. We estimated the vulnerability of dense grasslands in the Central Pyrenees, Spain, based on the connectivity loss (CL) among grassland patches that has occurred between the 1980s and the 2000s, as a result of i) an increase in biomass and greenness (CL-IBG), ii) woody encroachment (CL-WE), or iii) a decrease in biomass and greenness (CL-DBG). The environmental and grassland components of the agropastoral system were associated with the three processes, especially CL-IBG and CL-WE, in relation with the succession of vegetation toward climax communities, fostered by land abandonment and exacerbated by climate warming. CL-IBG occurred in pasture units that had a high proportion of dense grasslands and low current livestock pressure. CL-WE was most strongly associated with pasture units that had a high proportion of woody habitat and a large reduction in sheep and goat pressure between the 1930s and the 2000s. The economic component was correlated with the CL-WE and the CL-DBG; specifically, expensive pastures were the most productive and could maintain the highest rates of livestock grazing, which slowed down woody encroachment, but caused grassland degradation and DBG. In addition, CL-DBG was associated with geolocation of grasslands, mainly because livestock tend to graze closer to passable roads and buildings, where they cause grassland degradation. To properly manage the grasslands, an integrated management plan must be developed that includes an understanding of all components of the agropastoral system and takes into account all changes that have occurred in dense mountain grasslands. Addressing the problems individually risks the improvement of some grasslands and the deterioration of others.

The ability to eliminate undesired cells by apoptosis is a key mechanism to maintain organismal health and homeostasis. Failure to clear apoptotic cells efficiently can cause autoimmune diseases in mammals. Genetic studies in Caenorhabditis elegans have greatly helped to decipher the regulation of apoptotic cell clearance. In this study, we show that the loss of levamisole-sensitive acetylcholine receptor, but not of a typical neuronal acetylcholine receptor causes a reduction in the number of persistent cell corpses in worms suffering from an engulfment deficiency. This reduction is not caused by impaired or delayed cell death but rather by a partial restoration of the cell clearance capacity. Mutants in acetylcholine turn-over elicit a similar phenotype, implying that acetylcholine signaling is the process responsible for these observations. Surprisingly, tissue specific RNAi suggests that UNC-38, a major component of the levamisole-sensitive receptor, functions in the dying germ cell to influence engulfment efficiency. Animals with loss of acetylcholine receptor exhibit a higher fraction of cell corpses positive for the "eat-me" signal phosphatidylserine. Our results suggest that modulation by ion channels of ion flow across plasma membrane in dying cells can influence the dynamics of phosphatidylserine exposure and thus clearance efficiency.

We examine the large-scale distribution patterns of the nano- and microphytoplankton collected from 145 oceanic stations, at 3 m depth, the 20% light level and the depth of the subsurface chlorophyll maximum, during the Malaspina-2010 Expedition (December 2010-July 2011), which covered 15 biogeographical provinces across the Atlantic, Indian and Pacific oceans, between 35°N and 40°S. In general, the water column was stratified, the surface layers were nutrient-poor and the nano- and microplankton (hereafter phytoplankton, for simplicity, although it included also heterotrophic protists) community was dominated by dinoflagellates, other flagellates and coccolithophores, while the contribution of diatoms was only important in zones with shallow nutriclines such as the equatorial upwelling regions. We applied a principal component analysis to the correlation matrix among the abundances (after logarithmic transform) of the 76 most frequent taxa to synthesize the information contained in the phytoplankton data set. The main trends of variability identified consisted of: 1) A contrast between the community composition of the upper and the lower parts of the euphotic zone, expressed respectively by positive or negative scores of the first principal component, which was positively correlated with taxa such as the dinoflagellates Oxytoxum minutum and Scrippsiella spp., and the coccolithophores Discosphaera tubifera and Syracosphaera pulchra (HOL and HET), and negatively correlated with taxa like Ophiaster hydroideus (coccolithophore) and several diatoms, 2) a general abundance gradient between phytoplankton-rich regions with high abundances of dinoflagellate, coccolithophore and ciliate taxa, and phytoplankton-poor regions (second principal component), 3) differences in dominant phytoplankton and ciliate taxa among the Atlantic, the Indian and the Pacific oceans (third principal component) and 4) the occurrence of a diatom-dominated assemblage (the fourth principal component assemblage), including several pennate taxa, Planktoniella sol, Hemiaulus hauckii and Pseudo-nitzschia spp., in the divergence regions. Our findings indicate that consistent assemblages of co-occurring phytoplankton taxa can be identified and that their distribution is best explained by a combination in different degrees of both environmental and historical influences.

Aldehyde dehydrogenases (ALDHs) is a protein superfamily that catalyzes the oxidation of aldehyde molecules into their corresponding non-toxic carboxylic acids, and responding to different environmental stresses, offering promising genetic approaches for improving plant adaptation. The aim of the current study is the functional analysis for systematic identification of S. lycopersicum ALDH gene superfamily. We performed genome-based ALDH genes identification and functional classification, phylogenetic relationship, structure and catalytic domains analysis, and microarray based gene expression. Twenty nine unique tomato ALDH sequences encoding 11 ALDH families were identified, including a unique member of the family 19 ALDH. Phylogenetic analysis revealed 13 groups, with a conserved relationship among ALDH families. Functional structure analysis of ALDH2 showed a catalytic mechanism involving Cys-Glu couple. However, the analysis of ALDH3 showed no functional gene duplication or potential neo-functionalities. Gene expression analysis reveals that particular ALDH genes might respond to wounding stress increasing the expression as ALDH2B7. Overall, this study reveals the complexity of S. lycopersicum ALDH gene superfamily and offers new insights into the structure-functional features and evolution of ALDH gene families in vascular plants. The functional characterization of ALDHs is valuable and promoting molecular breeding in tomato for the improvement of stress tolerance and signaling.

Eelgrass (Zostera marina) populations occupying coastal waters of Alaska are separated by a peninsula and island archipelago into two Large Marine Ecosystems (LMEs). From populations in both LMEs, we characterize genetic diversity, population structure, and polarity in gene flow using nuclear microsatellite fragment and chloroplast and nuclear sequence data. An inverse relationship between genetic diversity and latitude was observed (heterozygosity: R2 = 0.738, P < 0.001; allelic richness: R2 = 0.327, P = 0.047), as was significant genetic partitioning across most sampling sites (θ = 0.302, P < 0.0001). Variance in allele frequency was significantly partitioned by region only in cases when a population geographically in the Gulf of Alaska LME (Kinzarof Lagoon) was instead included with populations in the Eastern Bering Sea LME (θp = 0.128-0.172; P < 0.003), suggesting gene flow between the two LMEs in this region. Gene flow among locales was rarely symmetrical, with notable exceptions generally following net coastal ocean current direction. Genetic data failed to support recent proposals that multiple Zostera species (i.e. Z. japonica and Z. angustifolia) are codistributed with Z. marina in Alaska. Comparative analyses also failed to support the hypothesis that eelgrass populations in the North Atlantic derived from eelgrass retained in northeastern Pacific Last Glacial Maximum refugia. These data suggest northeastern Pacific populations are derived from populations expanding northward from temperate populations following climate amelioration at the terminus of the last Pleistocene glaciation.

Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43-/- mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43-/- mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43-/- mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes.

Chicoric acid (CA) is a caffeoyl derivative previously described as having potential anti-diabetic properties. As similarities in cellular mechanism similarities between diabetes and aging have been shown, we explored on L6 myotubes the effect of CA on the modulation of intracellular pathways involved in diabetes and aging. We also determined its influence on lifespan of Caenorhabditis elegans worm (C. elegans). In L6 myotubes, CA was a potent reactive oxygen species (ROS) scavenger, reducing ROS accumulation under basal as well as oxidative stress conditions. CA also stimulated the AMP-activated kinase (AMPK) pathway and displayed various features associated with AMPK activation: CA (a) enhanced oxidative enzymatic defences through increase in glutathion peroxidase (GPx) and superoxide dismutase (SOD) activities, (b) favoured mitochondria protection against oxidative damage through up-regulation of MnSOD protein expression, (c) increased mitochondrial biogenesis as suggested by increases in complex II and citrate synthase activities, along with up-regulation of PGC-1α mRNA expression and (d) inhibited the insulin/Akt/mTOR pathway. As AMPK stimulators (e.g. the anti-diabetic agent meformin or polyphenols such as epigallocatechingallate or quercetin) were shown to extend lifespan in C. elegans, we also determined the effect of CA on the same model. A concentration-dependant lifespan extension was observed with CA (5-100 μM). These data indicate that CA is a potent antioxidant compound activating the AMPK pathway in L6 myotubes. Similarly to other AMPK stimulators, CA is able to extend C. elegans lifespan, an effect measurable even at the micromolar range. Future studies will explore CA molecular targets and give new insights about its possible effects on metabolic and aging-related diseases.

ObjectiveTo construct a metric of the impact of brain disorders on people's lives, based on the psychosocial difficulties (PSDs) that are experienced in common across brain disorders.Study designPsychometric study using data from a cross-sectional study with a convenience sample of 722 persons with 9 different brain disorders interviewed in four European countries: Italy, Poland, Spain and Finland. Questions addressing 64 PSDs were first reduced based on statistical considerations, patient's perspective and clinical expertise. Rasch analyses for polytomous data were also applied.SettingIn and outpatient settings.ResultsA valid and reliable metric with 24 items was created. The infit of all questions ranged between 0.7 and 1.3. There were no disordered thresholds. The targeting between item thresholds and persons' abilities was good and the person-separation index was 0.92. Persons' abilities were linearly transformed into a more intuitive scale ranging from zero (no PSDs) to 100 (extreme PSDs).ConclusionThe metric, called PARADISE 24, is based on the hypothesis of horizontal epidemiology, which affirms that people with brain disorders commonly experience PSDs. This metric is a useful tool to carry out cardinal comparisons over time of the magnitude of the psychosocial impact of brain disorders and between persons and groups in clinical practice and research.

BackgroundPersons with brain disorders experience significant psychosocial difficulties (PSD) in daily life, e.g. problems with managing daily routine or emotional lability, and the level of the PSD depends on social, physical and political environments, and psychologic-personal determinants. Our objective is to determine a brief set of environmental and psychologic-personal factors that are shared determinants of PSD among persons with different brain disorders.MethodsCross-sectional study, convenience sample of persons with either dementia, stroke, multiple sclerosis, epilepsy, migraine, depression, schizophrenia, substance dependence or Parkinson's disease. Random forest regression and classical linear regression were used in the analyses.Results722 subjects were interviewed in four European countries. The brief set of determinants encompasses presence of comorbidities, health status appraisal, stressful life events, personality changes, adaptation, self-esteem, self-worth, built environment, weather, and health problems in the family.ConclusionsThe identified brief set of common determinants of PSD can be used to support the implementation of cross-cutting interventions, social actions and policy tools to lower PSD experienced by persons with brain disorders. This set complements a recently proposed reliable and valid direct metric of PSD for brain disorders called PARADISE24.

The bacterial stringent response is triggered by deficiencies of available nutrients and other environmental stresses. It is mediated by 5'-triphosphate-guanosine-3'-diphosphate and 5'-diphosphate-guanosine-3'-diphosphate (collectively (p)ppGpp) and generates global changes in gene expression and metabolism that enable bacteria to adapt to and survive these challenges. Borrelia burgdorferi encounters multiple stressors in its cycling between ticks and mammals that could trigger the stringent response. We have previously shown that the B. burgdorferi stringent response is mediated by a single enzyme, RelBbu, with both (p)ppGpp synthase and hydrolase activities, and that a B. burgdorferi 297 relBbu null deletion mutant was defective in adapting to stationary phase, incapable of down-regulating synthesis of rRNA and could not infect mice. We have now used this deletion mutant and microarray analysis to identify genes comprising the rel regulon in B. burgdorferi cultured at 34°C, and found that transcription of genes involved in glycerol metabolism is induced by relBbu. Culture of the wild type parental strain, the relBbu deletion mutant and its complemented derivative at 34°C and 25°C in media containing glucose or glycerol as principal carbon sources revealed a growth defect in the mutant, most evident at the lower temperature. Transcriptional analysis of the glp operon for glycerol uptake and metabolism in these three strains confirmed that relBbu was necessary and sufficient to increase transcription of this operon in the presence of glycerol at both temperatures. These results confirm and extend previous findings regarding the stringent response in B. burgdorferi. They also demonstrate that the stringent response regulates glycerol metabolism in this organism and is likely crucial for its optimal growth in ticks.

We recently reported the rapid expansion of an HIV-1 subtype F cluster among men who have sex with men (MSM) in the region of Galicia, Northwest Spain. Here we update this outbreak, analyze near full-length genomes, determine phylogenetic relationships, and estimate its origin. For this study, we used sequences of HIV-1 protease-reverse transcriptase and env V3 region, and for 17 samples, near full-length genome sequences were obtained. Phylogenetic analyses were performed via maximum likelihood. Locations and times of most recent common ancestors were estimated using Bayesian inference. Among samples analyzed by us, 100 HIV-1 F1 subsubtype infections of monophyletic origin were diagnosed in Spain, including 88 in Galicia and 12 in four other regions. Most viruses (n = 90) grouped in a subcluster (Galician subcluster), while 7 from Valladolid (Central Spain) grouped in another subcluster. At least 94 individuals were sexually-infected males and at least 71 were MSM. Seventeen near full-length genomes were uniformly of F1 subsubtype. Through similarity searches and phylogenetic analyses, we identified 18 viruses from four other Western European countries [Switzerland (n = 8), Belgium (n = 5), France (n = 3), and United Kingdom (n = 2)] and one from Brazil, from samples collected in 2005-2011, which branched within the subtype F cluster, outside of both Spanish subclusters, most of them corresponding to recently infected individuals. The most probable geographic origin and age of the Galician subcluster was Ferrol, Northwest Galicia, around 2007, while the Western European cluster probably emerged in Switzerland around 2002. In conclusion, a recently expanded HIV-1 subtype F cluster, the largest non-subtype B cluster reported in Western Europe, continues to spread among MSM in Spain; this cluster is part of a larger cluster with a wide geographic circulation in diverse Western European countries.

In previous studies, we characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43) acting as a mitochondrial transcription factor. In in vitro and in vivo studies, we have shown that p43 increases mitochondrial transcription and mitochondrial biogenesis. In addition, p43 overexpression in skeletal muscle stimulates mitochondrial respiration and induces a shift in metabolic and contractile features of muscle fibers which became more oxidative.Here we have studied the influence of p43 overexpression in skeletal muscle of mice during aging. We report that p43 overexpression initially increased mitochondrial mass. However, after the early rise in mitochondrial DNA occurring at 2 months of age in transgenic mice, we observed a progressive decrease of mitochondrial DNA content which became 2-fold lower at 23 months of age relatively to control animals. Moreover, p43 overexpression induced an oxidative stress characterized by a strong increase of lipid peroxidation and protein oxidation in quadriceps muscle, although antioxidant enzyme activities (catalase and superoxide dismutase) were stimulated. In addition, muscle atrophy became detectable at 6 months of age, probably through a stimulation of the ubiquitin proteasome pathway via two muscle-specific ubiquitin ligases E3, Atrogin-1/MAFbx and MuRF1.Taken together, these results demonstrate that a prolonged stimulation of mitochondrial activity induces muscle atrophy. In addition, these data underline the importance of a tight control of p43 expression and suggest that a deregulation of the direct T3 mitochondrial pathway could be one of the parameters involved in the occurrence of sarcopenia.

BackgroundPeople with brain disorders - defined as both, mental disorders and neurological disorders experience a wide range of psychosocial difficulties (PSDs) (e.g., concentrating, maintaining energy levels, and maintaining relationships). Research evidence is required to show that these PSDs are common across brain disorders.ObjectivesTo explore and gain deeper understanding of the experiences of people with seven brain disorders (alcohol dependency, depression, epilepsy, multiple sclerosis, Parkinson's disease, schizophrenia, stroke). It examines the common PSDs and their influencing factors.MethodsSeventy seven qualitative studies identified in a systematic literature review and qualitative data derived from six focus groups are used to generate first-person narratives representing seven brain disorders. A theory-driven thematic analysis of these narratives identifies the PSDs and their influencing factors for comparison between the seven disorders.ResultsFirst-person narratives illustrate realities for people with brain disorders facilitating a deeper understanding of their every-day life experiences. Thematic analysis serves to highlight the commonalities, both of PSDs, such as loneliness, anger, uncertainty about the future and problems with work activities, and their determinants, such as work opportunities, trusting relationships and access to self-help groups.ConclusionsThe strength of the methodology and the narratives is that they provide the opportunity for the reader to empathise with people with brain disorders and facilitate deeper levels of understanding of the complexity of the relationship of PSDs, determinants and facilitators. The latter reflect positive aspects of the lives of people with brain disorders. The result that many PSDs and their influencing factors are common to people with different brain disorders opens up the door to the possibility of using cross-cutting interventions involving different sectors. This strengthens the message that 'a great deal can be done' to improve the lived experience of persons with brain disorders when medical interventions are exhausted.