Search

Dairy production in the UK has undergone substantial restructuring over the last few decades. Farming intensification has led to a reduction in the total numbers of farms and animals, while the average herd size per holding has increased. These ever-changing circumstances have important implications for the health and welfare of dairy cows, as well as the overall business performance of farms. For decision-making in dairy farming, it is essential to understand the underlying causes of the inefficiencies and their relative impact. The investigation of yield gaps regarding dairy cattle has been focused on specific causes. However, in addition to the risk of overestimating the impact of a specific ailment, this approach does not allow understanding of the relative contribution to the total, nor does it allow understanding of how well-described that gap is in terms of underlying causes. Using the English and Welsh dairy sectors as an example, this work estimates the Loss Gap-composed of yield losses and health expenditure - using a benchmarking approach and scenario analysis. The Loss Gap was estimated by comparing the current performance of dairy herds as a baseline with that of scenarios where assumptions were made about the milk production of cows, production costs, market prices, mortality, and expenditure related to health events. A deterministic model was developed, consisting of an enterprise budget, in which the cow was the unit, with milking herd and young stock treated separately. When constraining milk production, the model estimated an annual Loss Gap of £148 to £227 million for the whole sector. The reduction in costs of veterinary services and medicines, alongside herd replacement costs, were important contributors to the estimate with some variation between the scenarios. Milk price had a substantial impact in the estimate, with revenue from milk yield representing more than 30% of the Loss Gap, when milk price was benchmarked against that of the top performing farms. This framework provides the boundaries for understanding the relative burden from specific causes in English and Welsh dairy cattle, ensuring that the sum of the estimated losses due to particular problem does not exceed the losses from all-causes, health or non-health related.

Central nervous system (CNS) malignant neoplasms may lead to venous thromboembolism (VTE) and bleeding, which result in rehospitalization, morbidity and mortality. We aimed to assess the incidence of VTE and bleeding in this population.MethodsThis systematic review and meta-analysis (PROSPERO CRD42023423949) were based on a standardized search of PubMed, Virtual Health Library and Cochrane (n = 1653) in July 2023. After duplicate removal, data screening and collection were conducted by independent reviewers. The combined rates and 95% confidence intervals for the incidence of VTE and bleeding were calculated using the random effects model with double arcsine transformation. Subgroup analyses were performed based on sex, age, income, and type of tumor. Heterogeneity was calculated using Cochran's Q test and I2 statistics. Egger's test and funnel graphs were used to assess publication bias.ResultsOnly 36 studies were included, mainly retrospective cohorts (n = 30, 83.3%) from North America (n = 20). Most studies included were published in high-income countries. The sample size of studies varied between 34 and 21,384 adult patients, mostly based on gliomas (n = 30,045). For overall malignant primary CNS neoplasm, the pooled incidence was 13.68% (95%CI 9.79; 18.79) and 11.60% (95%CI 6.16; 18.41) for VTE and bleeding, respectively. The subgroup with elderly people aged 60 or over had the highest incidence of VTE (32.27% - 95%CI 14.40;53.31). The studies presented few biases, being mostly high quality. Despite some variability among the studies, we observed consistent results by performing sensitivity analysis, which highlight the robustness of our findings.ConclusionsOur study showed variability in the pooled incidence for both overall events and subgroup analyses. It was highlighted that individuals over 60 years old or diagnosed with GBM had a higher pooled incidence of VTE among those with overall CNS malignancies. It is important to note that the results of this meta-analysis refer mainly to studies carried out in high-income countries. This highlights the need for additional research in Latin America, and low- and middle-income countries.

[This corrects the article DOI: 10.1371/journal.pone.0225638.].

On the edge of causing the sixth big mass extinction event, the development of positive attitudes towards the conservation of intraspecific diversity from early ages is essential to overcome the biodiversity crisis we currently face. However, there is no information available on elementary school students' attitudes toward intraspecific diversity conservation nor is there a framework available to perform such analysis. For this study we designed, implemented, and evaluated an educational activity planned for third graders (8 to 13 years old) to explore the intraspecific diversity of vegetables and promote healthy eating habits. Additionally, a framework was developed to evaluate students' attitudes towards intraspecific diversity conservation and applied to semi-structured interviews conducted with students before and after engaging in the educational activity. In this paper we present a reliable framework, developed aligned with the ABC model of attitudes, based on literature, and adapted to elementary school students' responses, to evaluate students' attitudes toward intraspecific diversity. Our results show that, before the educational activity, most students choose a non-biodiverse option, justifying this choice with the affective component of attitudes: mostly emotional factors but also aesthetic and social/cultural factors. After the educational activity, we observed a significant increase in the frequency of students that choose the biodiverse option and that justified it with the cognitive component of attitudes: mainly with biology and health knowledge factors, but also with economic and ethical knowledge factors. Our findings support the positive impact of educational activities that explore vegetable varieties on students' attitudes toward intraspecific diversity conservation. This activity may also be used to foster education for sustainability and address socioscientific issues aligned with diverse sustainable development goals.

IntroductionRecently, the search for novel molecular markers in adult-type diffuse gliomas has grown substantially, yet with few novel breakthroughs. As the presence of a necrotic center is a differential diagnosis for more aggressive entities, we hypothesized that genes involved in necroptosis may play a role in tumor progression.AimGiven that MLKL is the executioner of the necroptotic pathway, we evaluated whether this gene would help to predict prognosis of adult gliomas patients.MethodsWe analyzed a publicly available retrospective cohort (n = 530) with Kaplan Meier survival analysis (pResultsWe determined that MLKL is an independent predictive prognostic marker for overall survival in these patients (HR: 2.56, p

Argyrosomus regius (commonly referred to as meagre), is one of Europe's largest coastal bony fish species and supports important recreational and commercial fisheries in the Atlantic and Mediterranean coasts. Demand for this species, and more recently for their swim bladders, has led to regional population declines and growing importance as an aquaculture species. Despite intense research in captivity, little is known about the spatial ecology of A. regius's wild population, including basic information such as vertical migrations and depth/temperature preferences. Previous research based on indirect data suggests a seasonal habitat shift from shallow to deeper waters, but this has never been validated through direct high-resolution movement data. In this study, we tagged 13 adult A. regius with pop-up satellite archival tags in the South of Portugal, which successfully returned data from 11 individuals including high-resolution data from six recovered tags (mean, range: 167 days, 28-301 days). We found that adults of this population spend 95.2% of their time between 5 and 75 m depth (mean ± SD, 30.9m ± 18.3m) and do not venture beyond 125 m. Across seasons, A. regius move across water temperatures between 13.3 and 24.8°C with a preferred thermal range between 14 and 18°C where they spent 75.4% of their time. The inferential modelling using this electronic data validated previous hypotheses by showing significant differences between a shallower and warmer summer habitat vs. a deeper and cooler winter habitat. Visual investigation of the diel effects on depth preferences suggests subtle changes in depth use between day and night during the warmer months of the year. We speculate that these patterns are in response to the species' behavioural ecology and physiology, reflecting the seasonal changes in water stratification and presence of prey, as well as on the species reproduction, which results in summer spawning aggregations in shallower areas.

IntroductionSentinel lymph node biopsy is the technique recommended for the axillary staging of patients with breast cancer in the initial stages without clinical axillary involvement. Three techniques are widely used globally to detect sentinel lymph nodes: patent blue, the radiopharmaceutical technetium 99 with gamma probe, and the combination of these two.ObjectivesTo evaluate the sentinel lymph node detection rate with an innovative technique: indocyanine green (ICG) associated with fluorescence in breast cancer patients, and compare it with patent blue and a combination of patent blue and indocyanine green.Methods99 patients were sequentially (not randomly) allocated into 3 arms with 33 patients submitted to sentinel lymph node techniques. One arm underwent patent blue dying, the other indocyanine green, and the third received a combination of both. The detection rates between arms were compared.ResultsThe detection rate in identifying the sentinel lymph node was 78.8% with patent blue, 93.9% with indocyanine green, and 100% with the combination. Indocyanine green identified two sentinel nodes in 48.5% of patients; the other groups more commonly had only one node identified. The mean time to sentinel lymph node identification was 20.6 ± 10.7 SD (standard deviation) minutes among patients submitted to the patent blue dye, 8.6 ± 6.6 minutes in the indocyanine green arm, and 10 ± 8.9 minutes in the combined group (PConclusionsThe sentinel lymph node detection rate by fluorescence using indocyanine green was 93.9%, considered adequate. The rates using patent blue, indocyanine green, and patent blue plus indocyanine green (combined) were significantly different, and the indocyanine green alone is also acceptable, since it has a good performance in sentinel lymph node identification and it can avoid tattooing, with a 100% sentinel lymph node detection rate when combined with patent blue.

PurposeTo analyze the long-term consequences of critical COVID-19, regarding physical, mental, cognitive and functional impairments, and to describe its evolution through time.MethodsProspective cohort study, with consecutive inclusion of patients admitted due to SARS-CoV-2 to intensive care units(ICU) of a tertiary-care center, between May/2020 and September/2021. All included patients were included in Physical and Rehabilitation Medicine(PRM) inpatient programs during ICU stay. Eligible patients were evaluated on PRM appointments 6 and 12 months after ICU discharge. In each visit, physical examination and a predefined set of scales were applied, aiming to comprehensively evaluate the three domains (physical, mental and cognitive) of post-intensive care syndrome and the patients' functionality. Statistical analysis encompassed descriptive and univariate analysis.ResultsA total of 42 patients were included: 66.7% males, mean age of 62 yo. In the physical domain, 6 months after ICU discharge, there was a significant reduction in quality of life (p-value = 0.034), muscle strength (p-value = 0.002), gait ability (p-valueConclusionCritical COVID-19 survivors present significant physical, mental and cognitive impairments 6 and 12 months after ICU discharge, despite their positive evolution through time.

The coastal intertidal ecosystem of the Bijagós Archipelago, Guinea-Bissau, one of the largest and most important in West Africa, sustains a considerable proportion of the migratory shorebird populations of the East Atlantic Flyway and operates as a nursery area for benthic fish in the region. The macrozoobenthos in these mudflats constitute the main food source for both groups so that spatial and temporal variation in their abundance and community composition is likely to influence the abundance and distribution of fish and birds. In this study we described the spatial and temporal dynamics in the density, biomass, and community composition of macrozoobenthos across six intertidal flats in three islands of the Bijagós Archipelago. Overall, the Bijagós Archipelago was characterised by a highly species-rich macrozoobenthic community, with ca. 88 taxa identified across all sites, reaching a mean density of 1871 ± 58.3 ind.m-2 (mean ± SE) and mean biomass of 5.65 ± 0.41 g of AFDM.m-2 (ash-free dry mass per m2), values much lower than what was described for nearby intertidal areas, namely the Band d'Arguin, Mauritania. Density and biomass of major macrozoobenthos classes (Bivalvia, Polychaeta, Malacostraca and Gastropoda) differed across sites and months, displaying an overall increase in density towards the final months of the dry season (March and April). Similarly, community composition also differed significantly between sites and throughout the season. The site with most distinct community composition (Adonga) supported low diversity and high abundance of a few bivalve species, whilst other two sites that hosted the most diverse communities, were also the most similar between them (Anrumai and Abu). These spatial and temporal patterns constitute an important baseline to improve knowledge of this intertidal ecosystem and will contribute towards a better understanding of the spatial and temporal distribution patterns of their consumers.

We aimed to evaluate the correlation of plasma levels of thiobarbituric acid reactive substances (TBARS) and reduced thiols with morbidity, mortality and immune response during and after SARS-CoV-2 infection. This was an observational study that included inpatients with SARS-CoV-2 infection older than 65 years. The individuals were followed up to the twelfth month post-discharge. Plasma levels of TBARS and reduced thiols were quantified as a measure of lipid and protein oxidation, respectively. Fatal and non-fatal events were evaluated during admission and at the third, sixth and twelfth month post-discharge. Differences in oxidative stress markers between the groups of interest, time to a negative RT-qPCR and time to significant anti-SARS-CoV-2 IgM titers were assessed. We included 61 patients (57% women) with a mean age of 83 years old. After multivariate analysis, we found differences in TBARS and reduced thiol levels between the comparison groups in fatal and non-fatal events during hospital admission. TBARS levels were also correlated with fatal events at the 6th and 12th months post-discharge. One year after hospital discharge, other predictors rather than oxidative stress markers were relevant in the models. The median time to reach significant anti-SARS-CoV-2 IgM titers was lower in patients with low levels of reduced thiols. Assessment of some parameters related to oxidative stress may help identify groups of patients with a higher risk of morbidity, mortality and delayed immune response during and after SARS-CoV-2 infection.

Background Severe coronavirus disease 2019 (COVID-19) patients frequently require mechanical ventilation (MV) and undergo prolonged periods of bed rest with restriction of activities during the intensive care unit (ICU) stay. Our aim was to address the degree of mobilization in critically ill patients with COVID-19 undergoing to MV support. Methods Retrospective single-center cohort study. We analyzed patients’ mobility level, through the Perme ICU Mobility Score (Perme Score) of COVID-19 patients admitted to the ICU. The Perme Mobility Index (PMI) was calculated [PMI = ΔPerme Score (ICU discharge–ICU admission)/ICU length of stay], and patients were categorized as “improved” (PMI > 0) or “not improved” (PMI ≤ 0). Comparisons were performed with stratification according to the use of MV support. Results From February 2020, to February 2021, 1,297 patients with COVID-19 were admitted to the ICU and assessed for eligibility. Out of those, 949 patients were included in the study [524 (55.2%) were classified as “improved” and 425 (44.8%) as “not improved”], and 396 (41.7%) received MV during ICU stay. The overall rate of patients out of bed and able to walk ≥ 30 meters at ICU discharge were, respectively, 526 (63.3%) and 170 (20.5%). After adjusting for confounders, independent predictors of improvement of mobility level were frailty (OR: 0.52; 95% CI: 0.29–0.94; p = 0.03); SAPS III Score (OR: 0.75; 95% CI: 0.57–0.99; p = 0.04); SOFA Score (OR: 0.58; 95% CI: 0.43–0.78; p < 0.001); use of MV after the first hour of ICU admission (OR: 0.41; 95% CI: 0.17–0.99; p = 0.04); tracheostomy (OR: 0.54; 95% CI: 0.30–0.95; p = 0.03); use of extracorporeal membrane oxygenation (OR: 0.21; 95% CI: 0.05–0.8; p = 0.03); neuromuscular blockade (OR: 0.53; 95% CI: 0.3–0.95; p = 0.03); a higher Perme Score at admission (OR: 0.35; 95% CI: 0.28–0.43; p < 0.001); palliative care (OR: 0.05; 95% CI: 0.01–0.16; p < 0.001); and a longer ICU stay (OR: 0.79; 95% CI: 0.61–0.97; p = 0.04) were associated with a lower chance of mobility improvement, while non-invasive ventilation within the first hour of ICU admission and after the first hour of ICU admission (OR: 2.45; 95% CI: 1.59–3.81; p < 0.001) and (OR: 2.25; 95% CI: 1.56–3.26; p < 0.001), respectively; and vasopressor use (OR: 2.39; 95% CI: 1.07–5.5; p = 0.03) were associated with a higher chance of mobility improvement. Conclusion The use of MV reduced mobility status in less than half of critically ill COVID-19 patients.

Arbovirus outbreaks in communities are affected by how vectors, hosts and non-competent species interact. In this study, we investigate how ecological interactions between species and epidemiological processes influence the invasion potential of a vector-borne disease. We use an eco-epidemiological model to explore the basic reproduction number R0 for a range of interaction strengths in key processes, using West Nile virus infection to parameterize the model. We focus our analysis on intra and interspecific competition between vectors and between hosts, as well as competition with non-competent species. We show that such ecological competition has non-linear effects on R0 and can greatly impact invasion risk. The presence of multiple competing vector species results in lower values for R0 while host competition leads to the highest values of risk of disease invasion. These effects can be understood in terms of how the competitive pressures influence the vector-to-host ratio, which has a positive relationship with R0. We also show numerical examples of how vector feeding preferences become more relevant in high competition conditions between hosts. Under certain conditions, non-competent hosts, which can lead to a dilution effect for the pathogen, can have an amplification effect if they compete strongly with the competent hosts, hence facilitating pathogen invasion in the community.

BackgroundFluoride has become widely used in dentistry because of its effectiveness in caries control. However, evidence indicates that excessive intake interferes with the metabolic processes of different tissues. Thus, this study aimed to investigate the effects of long-term exposure to F on the parotid salivary gland of mice, from the analysis of oxidative, proteomic and genotoxic parameters.Materials and methodsThe animals received deionized water containing 0, 10 or 50 mg/L of F, as sodium fluoride, for 60 days. After, parotid glands were collected for analysis of oxidative biochemistry, global proteomic profile, genotoxicity assessment and histopathological analyses.ResultsThe results revealed that exposure to fluoride interfered in the biochemical homeostasis of the parotid gland, with increased levels of thiobarbituric acid reactive species and reduced glutathione in the exposed groups; as well as promoted alteration of the glandular proteomic profile in these groups, especially in structural proteins and proteins related to oxidative stress. However, genotoxic assessment demonstrated that exposure to fluoride did not interfere with DNA integrity in these concentrations and durations of exposure. Also, it was not observed histopathological alterations in parotid gland.ConclusionsThus, our results suggest that long-term exposure to fluoride promoted modulation of the proteomic and biochemical profile in the parotid glands, without inducing damage to the genetic component. These findings reinforce the importance of rationalizing the use of fluorides to maximize their preventative effects while minimizing the environmental risks.

IntroductionThe Coronavirus Disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. Data on the mobility level of patients with COVID-19 in the intensive care unit (ICU) are needed.ObjectiveTo describe the mobility level of patients with COVID-19 admitted to the ICU and to address factors associated with mobility level at the time of ICU discharge.MethodsSingle center, retrospective cohort study. Consecutive patients admitted to the ICU with confirmed COVID-19 infection were analyzed. The mobility status was assessed by the Perme Score at admission and discharge from ICU with higher scores indicating higher mobility level. The Perme Mobility Index (PMI) was calculated [PMI = ΔPerme Score (ICU discharge-ICU admission)/ICU length of stay]. Based on the PMI, patients were divided into two groups: "Improved" (PMI > 0) and "Not improved" (PMI ≤ 0).ResultsA total of 136 patients were included in this analysis. The hospital mortality rate was 16.2%. The Perme Score improved significantly when comparing ICU discharge with ICU admission [20.0 (7-28) points versus 7.0 (0-16) points; P < 0.001]. A total of 88 patients (64.7%) improved their mobility level during ICU stay, and the median PMI of these patients was 1.5 (0.6-3.4). Patients in the improved group had a lower duration of mechanical ventilation [10 (5-14) days versus 15 (8-24) days; P = 0.021], lower hospital length of stay [25 (12-37) days versus 30 (11-48) days; P < 0.001], and lower ICU and hospital mortality rate. Independent predictors for mobility level were lower age, lower Charlson Comorbidity Index, and not having received renal replacement therapy.ConclusionPatients' mobility level was low at ICU admission; however, most patients improved their mobility level during ICU stay. Risk factors associated with the mobility level were age, comorbidities, and use of renal replacement therapy.

This study aimed to investigate the characteristics related to SARS-CoV-2 in Luanda, Angola. A total of 622 individuals were screened for SARS-CoV-2 from January to September 2020. Chi-square and logistic regression were used to identify the relationship between sociodemographic characteristics and SARS-CoV-2. Of the 622 tested, 14.3% tested positive. The infection rate was the same for both genders (14.3%). Individuals ≥40 years old, from non-urbanized areas, and healthcare professionals had a higher frequency of infection. The risk of infection was very high in individuals ≥60 years old (AOR: 23.3, 95% CI: 4.83-112), in women (AOR: 1.24, 95% CI: 0.76-2.04), in Luanda (AOR: 7.40, 95% CI: 1.64-33.4), and healthcare professionals (AOR: 1.27, 95% CI: 0.60-2.71), whereas a low risk was observed in individuals from urbanized areas (AOR: 0.44, 95% CI: 0.26-0.75). Our results suggest that Angolan authorities should implement a greater effort in non-urbanized areas and among healthcare professionals since when these individuals presented any indication for a COVID-19 test, such as fever/cough/myalgia, they were more likely to test positive for SARS-CoV-2 than having some other cause for symptoms.

[This corrects the article DOI: 10.1371/journal.pone.0249249.].

IntroductionCampylobacter spp. are zoonotic bacteria that cause gastroenteritis in humans worldwide, whose main symptom is diarrhea. In certain cases, extra intestinal manifestations may occur, such as Guillain Barré syndrome. The bacteria cause severe diarrhea mostly in children and in immunocompromised individuals. This review aims to address the prevalence of Campylobacter spp. in humans in sub-Saharan Africa. It also aims to understand the impact of HIV in the prevalence, as well as to report data on antibiotic resistance and propose research priorities.MethodsWe followed PRISMA guidelines to find studies on the occurrence of Campylobacter spp. in humans in all countries from sub-Saharan Africa. Studies published between 2000 and 2020 were searched in PubMed, Cochrane Library, CINAHL, African Index Medicus, African Journals Online, Google Scholar and Science Direct. We have conducted a random-effect meta-analysis and calculated the proportion of resistant isolates to different antibiotics.Results and discussionWe found 77 studies that described such occurrence in humans in 20 out of 53 sub-Saharan African countries. Campylobacter jejuni was the most prevalent species. Pooled prevalence was 9.9% (CI: 8.4%-11.6%). No major variations within the different sub-regions were found. Most studies reported Campylobacter spp. as the cause of diarrhea, mainly in children. Some studies reported the bacteria as a possible etiologic agent of acute flaccid paralysis and urinary tract infection. Campylobacter spp. presented a higher pooled prevalence in HIV infected patients, although not statistically significant. High proportions of resistant strains were reported for many antibiotics, including erythromycin and tetracycline.ConclusionCampylobacter spp. occur in sub-Saharan Africa, although information is scarce or inexistent for many countries. Research priorities should include investigation of the understudied species; extra intestinal manifestations; the impact of HIV infection and associated risk factors. Control strategies should be reinforced to contain the spread of this pathogen and drug resistance.

ObjectiveThis umbrella review was conducted to summarize the evidence and qualify the methodological quality of SR and SRMA published on small-sided games in team ball sports.MethodsA systematic review of Web of Science, PubMed, Cochrane Library, Scopus, and SPORTDiscus databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsFrom the 176 studies initially identified, 12 (eight SR and four SRMA) were fully reviewed, and their outcome measures were extracted and analyzed. Methodological quality (with the use of AMSTAR-2) revealed that seven reviews had low quality and five had critically low quality. Two major types of effects of SSGs were observed: (i) short-term acute effects and (ii) long-term adaptations. Four broad dimensions of analysis were found: (i) physiological demands (internal load); (ii) physical demands (external load) or fitness status; (iii) technical actions; and (iv) tactical behavior and collective organization. The psychological domain was reduced to an analysis of enjoyment. The main findings from this umbrella review revealed that SSGs present positive effects in improving aerobic capacity and tactical/technical behaviors, while neuromuscular adaptations present more heterogeneous findings. Factors such as sex, age group, expertise, skill level, or fitness status are also determinants of some acute effects and adaptations.ConclusionThe current umbrella review allowed to identify that most of the systematic review and meta-analysis conducted in SSGs presents low methodological quality considering the standards. Most of the systematic reviews included in this umbrella revealed that task constraints significantly change the acute responses in exercise, while SSGs are effective in improving aerobic capacity. Future original studies in this topic should improve the methodological quality and improve the experimental study designs for assessing changes in tactical/technical skills.

BackgroundNeurodegenerative diseases are sporadic hereditary conditions characterized by progressive dysfunction of the nervous system. Among the symptoms, vestibulopathy is one of the causes of discomfort and a decrease in quality of life. Hereditary spastic paraplegia is a heterogeneous group of hereditary degenerative diseases involving the disorder of a single gene and is characterized by the progressive retrograde degeneration of fibers in the spinal cord.ObjectiveTo determine the benefits of vestibular rehabilitation involving virtual reality by comparing pre intervention and post intervention assessments in individuals with hereditary spastic paraplegia.MethodsIn this randomized controlled clinical trial from the Rebec platform RBR-3jmx67 in which allocation concealment was performed and the evaluators be blinded will be included. The participants will include 40 patients diagnosed with hereditary spastic paraplegia. The interventions will include vestibular rehabilitation with virtual reality using the Wii® console, Wii-Remote and Wii Balance Board (Nintendo), and the studies will include pre- and post intervention assessments. Group I will include twenty volunteers who performed balance games. Group II will include twenty volunteers who performed balance games and muscle strength games. The games lasted from 30 minutes to an hour, and the sessions were performed twice a week for 10 weeks (total: 20 sessions).ResultsThis study provides a definitive assessment of the effectiveness of a virtual reality vestibular rehabilitation program in halting the progression of hereditary spastic paraplegia, and this treatment can be personalized and affordable.ConclusionThe study will determine whether a vestibular rehabilitation program with the Nintendo Wii® involving virtual reality can reduce the progressive effect of hereditary spastic paraplegia and serve as an alternative treatment option that is accessible and inexpensive. Rebec platform trial: RBR-3JMX67.

Scorpion venoms are mixtures of proteins, peptides and small molecular compounds with high specificity for ion channels and are therefore considered to be promising candidates in the venoms-to-drugs pipeline. Transcriptomes are important tools for studying the composition and expression of scorpion venom. Unfortunately, studying the venom gland transcriptome traditionally requires sacrificing the animal and therefore is always a single snapshot in time. This paper describes a new way of generating a scorpion venom gland transcriptome without sacrificing the animal, thereby allowing the study of the transcriptome at various time points within a single individual. By comparing these venom-derived transcriptomes to the traditional whole-telson transcriptomes we show that the relative expression levels of the major toxin classes are similar. We further performed a multi-day extraction using our proposed method to show the possibility of doing a multiple time point transcriptome analysis. This allows for the study of patterns of toxin gene activation over time a single individual, and allows assessment of the effects of diet, season and other factors that are known or likely to influence intraindividual venom composition. We discuss the gland characteristics that may allow this method to be successful in scorpions and provide a review of other venomous taxa to which this method may potentially be successfully applied.

AimsAssess trends and factors associated with interhospital transfers (IHT) and 30-day acute coronary syndrome (ACS) rehospitalizations in a national administrative database of patients admitted with an ACS between 2000-2015.Methods and resultsCohort study of patients hospitalized with ACS from 2000 to 2015, using a validated linkage algorithm to identify and link patient-level sequential hospitalizations occurring within 30 days from first admission (considering all hospitalizations within the 30-day timeframe as belonging to the same ACS episode of care-ACS-EC). From 212,481 ACS-EC, 42,670 (20.1%) had more than one hospitalization. ACS-EC hospitalization rates decreased throughout the study period (2000: 207.7/100.000 person-years to 2015: 185,8/100,000 person-years, p for trend ConclusionIHT and 30-day ACS rehospitalization reflect coronary referral network efficiency and access to specialized treatment. Identifying factors associated with higher likelihood of IHT and 30-day ACS rehospitalization may allow heightened surveillance and interventions to reduce rehospitalizations and inequities in access to specialized treatment.

Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in South East Asia. It has been suggested that, as a consequence of the inflammatory process during JEV infection, there is disruption of the blood-brain barrier (BBB) tight junctions that in turn allows the virus access to the central nervous system (CNS). However, what happens at early times of JEV contact with the BBB is poorly understood. In the present work, we evaluated the ability of both a virulent and a vaccine strain of JEV (JEV RP9 and SA14-14-2, respectively) to cross an in vitro human BBB model. Using this system, we demonstrated that both JEV RP9 and SA14-14-2 are able to cross the BBB without disrupting it at early times post viral addition. Furthermore, we find that almost 10 times more RP9 infectious particles than SA14-14 cross the model BBB, indicating this BBB model discriminates between the virulent RP9 and the vaccine SA14-14-2 strains of JEV. Beyond contributing to the understanding of early events in JEV neuroinvasion, we demonstrate this in vitro BBB model can be used as a system to study the viral determinants of JEV neuroinvasiveness and the molecular mechanisms by which this flavivirus crosses the BBB during early times of neuroinvasion.

BackgroundFluoride (F) is a naturally exists in nature but several studies have indicated it as an environmental toxicant to all leaving beings. Human F exposure has increased over the years since this ion has been used by industry on foods, beverages, toothpastes and on water supply. Although F is safe at optimal concentrations in water supply, human exposure to high levels could trigger neurofunctional deficits.Materials and methodsIn this study, human glial-like (U87) and neuronal-like (IMR-32) cells lineages were used to access F toxicity and CNS cell sensibility on both cell facing the same protocol. Cells were exposed to F over 3, 5 and 10 days on two different F concentrations. Fluoride exposed cells were evaluated by standard toxicity assays to cell viability, apoptosis, necrosis and general cell metabolism. Oxidative stress parameters were evaluated by ATP and ROS levels, lipid peroxidation, GSH/GSSG ratio and comet assay.ResultsNo changes were observed in IMR-32 at any given time while after 10 days of exposure to 0.22μg/mL, U87 glial-like cells showed signs of toxicity such as decreased cell viability by necrosis while general cell metabolism was increased. Oxidative stress parameters were next evaluated only on U87 glial-like cells after 10 days of exposure. F induced a decrease on ATP levels while no changes were observed on reactive oxygen species and lipid peroxidation. GSH/GSSG ratio was decreased followed by DNA damage both on 0.22μg/mL F.ConclusionsOur results suggest an important differential behavior of the distinct types of cells exposed to the different fluoride concentrations, pointing that the U87 glial-like cells as more susceptible to damage triggered by this ion.

INTRODUCTION:This study explores the possibility of a relationship between the sphericity degree of a target volume with the dose distribution. This relationship is evaluated based on the ratio isodose volume / target volume (IV/TV) and the metrics coverage, i.e., selectivity, gradient index, conformity index and mean dose when planning radiosurgery for vestibular schwannoma. METHODS:Sphericity degree (φ) was calculated for each target volume (TV) of 64 patients who underwent stereotactic radiosurgery (SRS) for vestibular schwannoma. The calculation of this parameter was developed using the theoretical definition for operational sphericity φ = VP/VCS. The values found are evaluated considering the following metrics:-Coverage (C), selectivity (S), gradient index (GI), Paddick conformity index (CIPaddick) and dose distribution (IV/TV). The planning was also carried out considering a spherical target volume defined in a spherical phantom. The spherical volume is the same as the target used in the treatment plan. The planning of the spherical target was considered as a reference plan to evaluate the dose distribution inside and outside the volume. RESULTS:It was possible to observe that the majority of target volumes has (ϕ) around 0,66-0,77, corresponding to 54,7% of the total. Considering the mean values for metrics, the results are: C = 0,98, S = 0,78, GI = 3,11 and CI = 0,81. The dose distribution was equivalent for treatment plans and reference plans. Quantitative analysis for IV/TV shows that these values are higher than 30% for treatment plans where shot density is large. CONCLUSION:This study demonstrates that de sphericity degree (φ) can be related to the dose distribution (IV/TV). Therefore the sphericity degree is a good parameter to evaluate the dose distribution of a plan for vestibular schwannoma treatment, considering the reference plan as being a spherical target using a leksell gamma knife® perfexion (LGKP). This study shows that the sphericity degree offers important information of the dose distribution outside and inside the target volume. This is not evaluated by the other parameters already implemented as metric to analyzing the GKP plans.

Autophagy is a mechanism responsible for intracellular degradation and recycling of macromolecules and organelles, essential for cell survival in adverse conditions. More than 40 autophagy-related (ATG) genes have been identified and characterized in fungi, among them ATG4 and ATG8. ATG4 encodes a cysteine protease (Atg4) that plays an important role in autophagy by initially processing Atg8 at its C-terminus region. Atg8 is a ubiquitin-like protein essential for the synthesis of the double-layer membrane that constitutes the autophagosome vesicle, responsible for delivering the cargo from the cytoplasm to the vacuole lumen. The contributions of Atg-related proteins in the pathogenic yeast in the genus Cryptococcus remain to be explored, to elucidate the molecular basis of the autophagy pathway. In this context, we aimed to investigate the role of autophagy-related proteins 4 and 8 (Atg4 and Atg8) during autophagy induction and their contribution with non-autophagic events in C. neoformans. We found that Atg4 and Atg8 are conserved proteins and that they interact physically with each other. ATG gene deletions resulted in cells sensitive to nitrogen starvation. ATG4 gene disruption affects Atg8 degradation and its translocation to the vacuole lumen, after autophagy induction. Both atg4 and atg8 mutants are more resistant to oxidative stress, have an impaired growth in the presence of the cell wall-perturbing agent Congo Red, and are sensitive to the proteasome inhibitor bortezomib (BTZ). By that, we conclude that in C. neoformans the autophagy-related proteins Atg4 and Atg8 play an important role in the autophagy pathway; which are required for autophagy regulation, maintenance of amino acid levels and cell adaptation to stressful conditions.

The hospitalizations are part of cancer care and has been studied by researchers worldwide. A better understanding about their associated factors may help to achieve improvements on this area. The aims of this study were to investigate the association between demographic and clinical characteristics and hospitalizations, as well as between these characteristics and the length of stay (LOS), within the first year of outpatient treatment, for the most incident cancers in the Brazilian population. In this cohort study, we investigated 417,477 patients aged 19 years or more, who started outpatient cancer treatment, from 2010-2014, for breast, prostate, colorectal, cervix, lung and stomach cancers. The outcomes evaluated were: i) Hospitalizations within the first year of outpatient cancer treatment; and ii) LOS of the hospitalized patients. It was performed a binary logistic regression to evaluate the association between the explanatory variables and the hospitalizations and a negative binomial regression to evaluate their influence on the length of hospital stay. The hospitalizations occurred for 34% of patients, with a median of LOS of 6 days (IQR: 2-15). Female patients were 16% less likely to be hospitalized (OR: 0.84; 95% CI: 0.82-0.86), with lower average of LOS (AR: 0.98; 95% CI: 0.97-0.99), each additional year of age reduced in 2% the hospitalization odds (OR: 0.98; 95% CI: 0.98-0.99) and in 1% the average of LOS (AR: 0.99; 95% CI: 0.98-0.99), patients from South region had twice more chances of hospitalization than from North region (OR: 2.01; 95% CI: 1.93-2.10) and patients with colorectal cancer had greater probability of hospitalization (OR: 4.42; 95% CI: 4.27-4.48), with the highest average of LOS (AR: 1.37; 95% CI: 1.35-1.40). In view of our results, we consider that the government must expand the policies with potential to reduce the number of hospitalizations.

This paper employs a solution to the agent-guidance problem in an environment with obstacles, whose avoidance techniques have been extensively used in the last years. There is still a gap between the solution times required to obtain a trajectory and those demanded by real world applications. These usually face a tradeoff between the limited on-board processing performance and the high volume of computing operations demanded by those real-time applications. In this paper we propose a deferred decision-based technique that produces clusters used for obstacle avoidance as the agent moves in the environment, like a driver that, at night, enlightens the road ahead as her/his car moves along a highway. By considering the spatial and temporal relevance of each obstacle throughout the planning process and pruning areas that belong to the constrained domain, one may relieve the inherent computational burden of avoidance. This strategy reduces the number of operations required and increases it on demand, since a computationally heavier problem is tackled only if the simpler ones are not feasible. It consists in an improvement based solely on problem modeling, which, by example, may offer processing times in the same order of magnitude than the lower-bound given by the relaxed form of the problem.

BackgroundRelapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS).Methods and findingsWe conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; PConclusionsThis retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.

This paper proposes a dynamic model to describe and forecast the dynamics of the coronavirus disease COVID-19 transmission. The model is based on an approach previously used to describe the Middle East Respiratory Syndrome (MERS) epidemic. This methodology is used to describe the COVID-19 dynamics in six countries where the pandemic is widely spread, namely China, Italy, Spain, France, Germany, and the USA. For this purpose, data from the European Centre for Disease Prevention and Control (ECDC) are adopted. It is shown how the model can be used to forecast new infection cases and new deceased and how the uncertainties associated to this prediction can be quantified. This approach has the advantage of being relatively simple, grouping in few mathematical parameters the many conditions which affect the spreading of the disease. On the other hand, it requires previous data from the disease transmission in the country, being better suited for regions where the epidemic is not at a very early stage. With the estimated parameters at hand, one can use the model to predict the evolution of the disease, which in turn enables authorities to plan their actions. Moreover, one key advantage is the straightforward interpretation of these parameters and their influence over the evolution of the disease, which enables altering some of them, so that one can evaluate the effect of public policy, such as social distancing. The results presented for the selected countries confirm the accuracy to perform predictions.

The aim of this retrospective study was to evaluate the survival and associated factors for the longevity of direct posterior restorations and to verify whether the geographic location of public health units could influence the long-term survival of such restorations. Data were extracted from electronic patient files of the Brazilian public oral health services. The sample comprised 2,405 class I and II restorations performed 4 to 24 years ago (mean, 8.9 years) in 351 patients (6.8 teeth/patient) across 12 public health units located in different city regions (42 professionals-55 restorations). The restoration was considered successful if it had not been repaired or replaced at the time of evaluation; failure was defined as replacement of the restoration, the need for endodontic treatment, tooth/restoration fracture or tooth extraction. Data were analyzed using the Kaplan-Meier test for restoration survival and Cox regression to evaluate the factors associated with failure. The majority of the restorations involved the use of amalgam (85%), involved a single face (70%), and were without pulp/dentin capping (85%). The overall survival rate was 95%, and the mean observation time was 8.9 years. The restoration survival was 79% (95% CI: 60.6-89.5) over 24 years, and the mean survival time was 22.2 years (95% CI: 21.9-22.6 years). The annual failure rate up to 24 years was 0.9%. After the adjustment, only the number of restored faces and the geographic location where the restoration was performed remained associated with failure of the restoration. The direct posterior restorations performed at the evaluated public health service units presented high survival rates. The restorations of people with lower access to POHS had lower survival rates. Class I restorations presented higher survival rates than class II restorations with two or more faces, regardless of the restorative material used.

The Brazilian stingless bee Scaptotrigona depilis requires the brood cells-associated fungus Zygosaccharomyces sp. as steroid source for metamorphosis. Besides the presence of Zygosaccharomyces sp., other fungi inhabit S. depilis brood cells, but their biological functions are unknown. Here we show that Candida sp. and Monascus ruber, isolated from cerumen of S. depilis brood provisions, interact with Zygosaccharomyces sp. and modulate its growth. Candida sp. produces volatile organic compounds (VOCs) that stimulate Zygosacchromyces sp. development. Monascus ruber inhibits Zygosacchromyces sp. growth by producing lovastatin, which blocks steroid biosynthesis. We also observed that in co-cultures M. ruber inhibits Candida sp. through the production of monascin. The modulation of Zygosaccharomyces sp. growth by brood cell-associated fungi suggests their involvement in S. depilis larval development. This tripartite fungal community opens new perspectives in the research of microbial interactions with bees.

Studies on diabetic nephropathy rarely take into account that the co-existence of diabetes and hypertension is frequent and further aggravates the prognosis of renal dysfunction. Adenosine can activate four subtypes of adenosine receptors (A1, A2A, A2B and A3) and has been implicated in diabetic nephropathy. However, it is not known if, in hypertensive conditions, diabetes alters the presence/distribution profile of renal adenosine receptors. The aim of this work was to describe the presence/distribution profile of the four adenosine receptors in six renal structures (superficial/deep glomeruli, proximal/distal tubules, loop of Henle, collecting tubule) of the hypertensive kidney and to evaluate whether it is altered by diabetes. Immunoreactivities against the adenosine receptors were analyzed in six renal structures from spontaneously hypertensive rats (SHR, the control group) and from SHR rats with diabetes induced by streptozotocyin (SHR-STZ group). Data showed, for the first time, that all adenosine receptors were present in the kidney of SHR rats, although the distribution pattern was specific for each adenosine receptor subtype. Also, induction of diabetes in the SHR was associated with downregulation of adenosine A2A receptors, which might be relevant for the development of hypertensive diabetic nephropathy. This study highlights the adenosine A2A receptors as a potential target to explore to prevent and/or treat early diabetes-induced hyperfiltration, at least in hypertensive conditions.

BACKGROUND:Female breast cancer is the most common cancer in Latin American and Caribbean (LAC) countries and is the leading cause of cancer deaths. The high mortality-to-incidence ratio in the regions is associated with mainly the high proportion of advanced stage diagnosis, and also to inadequate access to health care. In this study we aimed to systematically review the proportion of advanced stage (III-IV) at diagnosis (pas) and the five-year stage-specific survival estimates of breast cancer in LAC countries. METHODS:We searched MEDLINE, Embase, and LILACS (Latin American and Caribbean Health Science Literature) to identify studies, in any language, indexed before Nov 5, 2018. We also conducted manual search by reviewing citations of papers found. pas was summarized by random effects model meta-analysis, and meta-regression analysis to identify sources of variation. Stage-specific survival probabilities were described as provided by study authors, as it was not possible to conduct meta-analysis. PROSPERO CRD42017052493. RESULTS:For pas we included 63 studies, 13 of which population-based, from 22 countries comprising 221,255 women diagnosed from 1966 to 2017. The distribution of patients by stage varied greatly in LAC (pas 40.8%, 95%CI 37.0% to 44.6%; I2 = 99%; p

Plasmodium (P.) falciparum malaria during pregnancy has been frequently associated with severe consequences such as maternal anemia, abortion, premature birth, and reduced birth weight. Placental damage promotes disruption of the local homeostasis; though, the mechanisms underlying these events are still to be elucidated. Autophagy is a fundamental homeostatic mechanism in the natural course of pregnancy by which cells self-recycle in order to survive in stressful environments. Placentas from non-infected and P. falciparum-infected women during pregnancy were selected from a previous prospective cohort study conducted in the Brazilian Amazon (Acre, Brazil). Newborns from infected women experienced reduced birth weight (P = 0.0098) and placental immunopathology markers such as monocyte infiltrate (P < 0.0001) and IL-10 production (P = 0.0122). The placentas were evaluated for autophagy-related molecules. As a result, we observed reduced mRNA levels of ULK1 (P = 0.0255), BECN1 (P = 0.0019), and MAP1LC3B (P = 0.0086) genes in placentas from P. falciparum-infected, which was more striking in those diagnosed with placental malaria. Despite the protein levels of these genes followed the same pattern, the observed reduction was not statistically significant in placentas from P. falciparum-infected women. Nevertheless, our data suggest that chronic placental immunopathology due to P. falciparum infection leads to autophagy dysregulation, which might impair local homeostasis during malaria in pregnancy that may result in poor pregnancy outcomes.

INTRODUCTION:Obesity and overweight strongly contribute to increasing cardiovascular morbidity and mortality, and are becoming a worldwide health issue. The prevalence of obesity has increased dramatically in Latin America. Child obesity is a major issue. Fast food is strongly suspected of contributing to this epidemic of obesity, although there is a lack of evidence. METHODS:We studied the correlation between the number of McDonald restaurants and overweight and obesity prevalence by region stratified by gender and age. Data on prevalences were obtained within national studies conducted by the Brazilian Ministry of Health. Three age sub-groups were analyzed: 5 to 9-year-olds, 10 to 19-year-olds and over 19-year-olds. RESULTS:There was a very strong positive correlation between overweight rates and the number of McDonald restaurants for both males and females between 5 and 9 years old (R2 respectively = 0.92 and 0.84) and a strong positive correlation for females between 10 and 19 years old (R2 = 0.68). There was a very strong positive correlation between obesity rates and the number of McDonald restaurants for males between 5 and 9 years old (R2 = 0.95). This positive correlation was strong for both males and females between 10 and 19 years old (R2 respectively = 0.77 and 0.63). Other correlations were not significant. CONCLUSION:A strong correlation between the prevalence of overweight and obesity and the number of McDonald restaurants was found for Brazilian children and was most important within the group of youngest children. These results should be taken into consideration by education and prevention campaigns.

IntroductionTuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. The advent of immunobiologic therapy with TNF inhibitors agents, has been associated with a significant increase in incident cases of tuberculosis in this population.ObjectiveTo estimate the incidence of tuberculosis in patients receiving TNF inhibitors therapy for rheumatic diseases. As secondary objectives, we sought to evaluate mortality and the clinical impact of screening for latent tuberculosis infection.MethodsThis retrospective study included patients with rheumatic diseases of Public Health System from the Brazilian state, a high TB incidence area, who received prescriptions of TNF inhibitors agents between 2006 and 2016.ResultsA total of 5853 rheumatic disease patients were included. Patients were predominantly women (68.7%) aged 49.5 (± 14.7) years old. Forty-three cases of TB were found (2.86 cases per 1000 person-years; 18 times higher than in the general population). Adalimumab and certolizumab users presented a higher risk for TB development compared to etanercept users (RR: 3.11, 95%CI 1.16-8.35; 7.47, 95%CI 1.39-40.0, respectively). In a subgroup of patients, screening for latent tuberculosis infection was performed in 86% of patients, and 30.2% had a positive tuberculin skin test. Despite latent TB treatment, TB was diagnosed in 2 out of 74 (2.7%) patients. Overall, TB diagnosis did not increase mortality.ConclusionIn this population-based study of rheumatic disease patients from a high incident area, TNF inhibitor exposure was associated with an 18-time increased TB incidence. Adalimumab and certolizumab were associated with greater and earlier TB diagnosis compared to etanercept.

BackgroundTherapeutic footwear becomes the first treatment line in the prevention of diabetic foot ulcer and future complications of diabetes. Previous studies and the International Working Group on the Diabetic Foot have described therapeutic footwear as a protective factor to reduce the risk of re-ulceration. In this study, we aimed to analyze the efficacy of a rigid rocker sole to reduce the recurrence rate of plantar ulcers in patients with diabetic foot.MethodsBetween June 2016 and December 2017, we conducted a randomized controlled trial in a specialized diabetic foot unit.Participants and interventionFifty-one patients with diabetic neuropathy who had a recently healed plantar ulcer were randomized consecutively into the following two groups: therapeutic footwear with semi-rigid sole (control) or therapeutic footwear with a rigid rocker sole (experimental). All patients included in the study were followed up for 6 months (one visit each 30 ± 2 days) or until the development of a recurrence event.Main outcome and measurePrimary outcome measure was recurrence of ulcers in the plantar aspect of the foot.FindingsA total of 51 patients were randomized to the control and experimental groups. The median follow-up time was 26 [IQR-4.4-26.1] weeks for both groups. On an intention-to-treat basis, 16 (64%) and 6 (23%) patients in the control and experimental groups had ulcer recurrence, respectively. Among the group with >60% adherence to therapeutic footwear, multivariate analysis showed that the rigid rocker sole improved ulcer recurrence-free survival time in diabetes patients with polyneuropathy and DFU history (P = 0.019; 95% confidence interval, 0.086-0.807; hazard ratio, 0.263).ConclusionsWe recommend the use of therapeutic footwear with a rigid rocker sole in patients with diabetes with polyneuropathy and history of diabetic foot ulcer to reduce the risk of plantar ulcer recurrence.Trial registrationClinicalTrials.gov NCT02995863.

BackgroundPrison inmates are considered a high-risk population for blood-borne and enterically transmitted infections before and during their imprisonment. Hepatitis E virus (HEV) prevalence is unknown among French inmates, whereas a reassessment of human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalences is required to describe the epidemiologic evolution in this high-risk population.MethodsA prospective survey was conducted from June to December 2017 in Fresnes prison, a penitentiary center with 2,581 inmates. In addition to HIV, HAV, HBV and HCV testing, which is offered to all patients at admission, we systematically offered HEV screening. Retrospective serological data for HIV, HBV and HCV, collected annually from 2014 to 2017, were also used to assess evolution.ResultsIn 2017, 1,093 inmates were screened for HEV, HIV, HAV, HBV and HCV. Prevalences in this population were 8.2%, 1.3%, 62.7%, 1.9% and 2.9%, respectively. HEV seroprevalence increased with age (pConclusionsCompared to the reported prevalence in French blood donors, HEV seroprevalence was remarkably low in French inmates. HIV, HAV, HBV and HCV prevalences among prisoners were higher than reported in the general population.

BackgroundThe diagnosis of sickle cell disease (SCD) is made by hemoglobin assays such as high-performance liquid chromatography (HPLC), isoelectric focusing and cellulose acetate or citrate agar electrophoresis. These assays are easy to perform and used in large-scale newborn screening in many countries. These tests however may not easily differentiate Sβ0 thalassemia from SS or identify other hemoglobin variants, and in this case, hemoglobin (HBB) gene sequencing may be necessary.ObjectivesTo develop a high throughput DNA based confirmatory assay for SCD and to detect mutations in the HBB gene.MethodsWe developed an automated pyrosequencing technique (PyS) based on QIAGEN technology (Hilden, Germany) to detect homozygous or heterozygous hemoglobin S mutations as well as hemoglobin C mutations. The technique was tested on 2,748 samples from patients enrolled in a multi-center SCD cohort in Brazil. Patients were previously tested using HPLC to diagnose SCD as part of routine clinical care. Any subjects with discrepant results between HPLC and PyS or with heterozygous hemoglobin S detected had Sanger sequencing of the HBB gene.ResultsWe identified 168 samples with discrepant results between HPLC and PyS and 100 with concordant PyS = heterozygous S and HPLC, which would suggest SB-thalassemia or other heterozygous S variants. The PyS assay correctly identified 1906 (98.7%) of the 1930 HbSS and 628 (98.7%) of the 636 HbSC samples. Of the 179 remaining samples, PyS correctly indicated S heterozygosis in 165 (92.2%). Of the 165 heterozygous S samples confirmed by Sanger as consistent with Sβ thalassemia genotype, 84 samples were classified as Sβ0 thalassemia and 81 as Sβ+ thalassemia. The most frequent beta thalassemia mutations of Sβ0 and Sβ+ were HBB: c.118C>T (Gln40Stop) and HBB c.92 + 6T> C, respectively.DiscussionThe PyS proved to be satisfactory for large-scale confirmatory testing of hemoglobin mutation. Moreover, with this study we were able to describe the most common β+ and β0 mutations in SCD patients with Sβ-thalassemia in a large multi-institutional SCD cohort in Brazil.

Highly pathogenic avian influenza (HPAI) virus subtype H7N3 has been circulating in poultry in Mexico since 2012 and vaccination has been used to control the disease. In this study, eight Mexican H7N3 HPAI viruses from 2015-2017 were isolated and fully sequenced. No evidence of reassortment was detected with other avian influenza (AI) viruses, but phylogenetic analyses show divergence of all eight gene segments into three genetic clusters by 2015, with 94.94 to 98.78 percent nucleotide homology of the HA genes when compared to the index virus from 2012. The HA protein of viruses from each cluster showed a different number of basic amino acids (n = 5-7) in the cleavage site, and six different patterns at the predicted N-glycosylation sites. Comparison of the sequences of the Mexican lineage H7N3 HPAI viruses and American ancestral wild bird AI viruses to characterize the virus evolutionary dynamics showed that the nucleotide substitution rates in PB2, PB1, PA, HA, NP, and NS genes greatly increased once the virus was introduced into poultry. The global nonsynonymous and synonymous ratios imply strong purifying selection driving the evolution of the virus. Forty-nine positively selected sites out of 171 nonsynonymous mutations were identified in the Mexican H7N3 HPAI viruses, including 7 amino acid changes observed in higher proportion in North American poultry origin AI viruses isolates than in wild bird-origin viruses. Continuous monitoring and molecular characterization of the H7N3 HPAI virus is important for better understanding of the virus evolutionary dynamics and further improving control measures including vaccination.

[This corrects the article DOI: 10.1371/journal.pone.0139837.].

Social Network Analysis establishes a network system and provides information about the relationships (edges) between system components (nodes). Although nodes usually correspond to actors within the network (e.g., the players), it is possible to stipulate game actions as nodes, thus creating a network of the flow of game actions. In this study, Eigenvector Centrality (a form of weighted centrality that considers n-order connections) was used to identify differences in the centrality of distinct game actions within each of the six game complexes of volleyball. Thirteen matches (46 sets, 2,049 rallies) of the final round of the 2015 FIVB's World Grand Prix (Women) were analyzed. Results showed that analyzing actions as actors (i.e., nodes) offers a clear and comprehensive understanding of game flow and poses an interesting alternative to mainstream research where players are considered nodes. Functional differences between the six game complexes were highlighted, denoting the validity of such division. Out-of-system playing (i.e., having to set the attack under non-ideal conditions, e.g., in KI, KII, KIII and KIV), emerged as a regularity of the game and should be translated into the training process.

Risk of mortality in the setting of acute kidney injury (AKI) in cats and dogs remains unclear.To evaluate the incidence of mortality in cats and dogs with AKI based on etiology (i.e. infectious versus non-infectious; receiving dialysis versus conservative treatment).Ovid Medline, EMBASE, and LILACS were searched up to July 2016. Articles were deemed eligible if they were case series studies evaluating the incidence of all-cause mortality in cats and dogs with AKI, regardless of etiology or the nature of treatment.Eighteen case series involving 1,201animalsproved eligible. The pooled proportions for overall mortality were: cats53.1% [95% CI 0.475, 0.586; I2 = 11,9%, p = 0.3352]; dogs 45.0% [95% CI 0.33, 0.58; I2 = 91.5%, P < 0.0001]. A non-significant increase in overall mortality risk was found among dialysed animals relative to those managed with conservative treatment, independent of animal type and the etiology of their AKI. The pooled proportions for overall mortality according to etiology, regardless of treatment type, were: AKI due infectious etiology for cats and dogs, 19.2% [95% CI 0.134, 0.258; I2 = 37.7%, P = 0.0982]; AKI due non-infectious etiology for cats and dogs, 59.9% [95% CI 0.532, 0.663; I2 = 51.0%, P = 0.0211].Our findings suggest higher rates of overall mortality in cats and dogs with AKI due to non-infectious etiologies relative to infectious etiologies, and showed non-significant differences in terms of higher rates associated with dialysis compared to conservative management. Further investigations regarding optimal time to initiate dialysis and the development of clinical models to prognosticate the course of disease and guide optimal treatment initiation for less severe cases of AKI in cats and dogs is warranted.

Mortality of fish has been reported in tide pools during warm days. That means that tide pools are potential ecological traps for coastal organisms, which happen when environmental changes cause maladaptive habitat selection. Heat-waves are predicted to increase in intensity, duration and frequency, making it relevant to investigate the role of tide pools as traps for coastal organisms. However, heat waves can also lead to acclimatization. If organisms undergo acclimatization prior to being trapped in tide pools, their survival chances may increase. Common tide pool species (46 species in total) were collected at a tropical and a temperate area and their upper thermal limits estimated. They were maintained for 10 days at their mean summer sea surface temperature +3°C, mimicking a heat-wave. Their upper thermal limits were estimated again, after this acclimation period, to calculate each species' acclimation response. The upper thermal limits of the organisms were compared to the temperatures attained by tide pool waters to investigate if 1) tide pools could be considered ecological traps and 2) if the increase in upper thermal limits elicited by the acclimation period could make the organisms less vulnerable to this threat. Tropical tide pools were found to be ecological traps for an important number of common coastal species, given that they can attain temperatures higher than the upper thermal limits of most of those species. Tide pools are not ecological traps in temperate zones. Tropical species have higher thermal limits than temperate species, but lower acclimation response, that does not allow them to survive the maximum habitat temperature of tropical tide pools. This way, tropical coastal organisms seem to be, not only more vulnerable to climate warming per se, but also to an increase in the ecological trap effect of tide pools.

BACKGROUND:Vitamin D deficiency is common in older adults and has been linked with frailty and obesity, but it remains to be studied whether frail obese older adults are at higher risk of vitamin D deficiency. Therefore, the aim of this study is to explore the association between frailty, obesity indices and serum 25(OH)D concentrations. METHODS:1447 individuals with 65 years or older, participating in a cross-sectional study (Nutrition UP 65) were included. Frailty, according to Fried et al., body mass index (BMI), waist circumference (WC), body roundness index (BRI) and body shape index (ABSI) were evaluated. A stepwise multinomial logistic regression was carried out to quantify the association between 25(OH)D quartiles and independent variables. RESULTS:Median 25(OH)D levels were lower in individuals presenting both frailty and obesity (p

BACKGROUND:Multiple Sclerosis (MS) is a disease that appreciably impacts on the quality of life of patients and is associated with high expenditure. MS is a chronic multifactorial disease, characterized by inflammation, demyelination and axonal loss. The Brazilian public health system provides pharmacological treatment as well as hospital and outpatient care for patients with relapsing-remitting and secondary progressive multiple sclerosis. However, we are not aware of any previous publications assessing total direct medical costs in patients with a long follow-up within the Brazilian healthcare system. Consequently, the objective is to analyze public spending on patients with MS to guide stakeholders in future investment and disinvestment decisions. METHODS AND FINDINGS:We retrospectively analyzed public Brazilian spending on patients with MS between 2000 and 2015 using the patient-centered registry of all patients in the public health system (SUS) obtained through deterministic-probabilistic record linkage of the Outpatient Information System, Hospital Information System and Mortality Information Systems in Brazil. Descriptive data analysis and a multiple linear regression model was performed to evaluate the associations between the mean annual cost per patient and the clinical and demographic variables. The suitability of the model was verified from a residue analysis and the level of significance adopted was 5%. RESULTS:28,401 patients were identified and subsequently 23,082 patients were analyzed. The majority of the patients were female (73.3%), lived in the southeast region (58.9%), had a mean age of 36.8 (± 12.2) years and started treatment using one of the interferons beta (78.9%). The total direct medical cost spending in the sixteen years of the follow-up was US $ 2,308,393,465.60, and the mean annual expenditure per patient was US $ 13,544.40 (± 4,607.05). In the best fit model (p

The present study aims to clarify the association of vitamin D status with functionality, measured through gait speed and hand grip strength, in a sample of older adults, considering sex-specific characteristics and the potential confounding effect of lifestyle factors, disease, skin phenotype, season of blood collection and vitamin D supplementation. The Nutrition UP 65 cross-sectional study was conducted in a population-based sample of 1,425 older adults ≥ 65 years old. Serum levels of 25-hydroxyvitamin D were quantified through electrochemiluminescence immunoassay. Multinomial logistic regressions were carried out using quartiles of gait speed and of hand grip strength as dependent variables. Participants at risk of vitamin D inadequacy (30.0-49.9 nmol/L) and deficiency (< 30.0 nmol/L) presented higher adjusted odds ratio of the lowest values of gait speed and hand grip strength than those with adequate vitamin D levels (≥ 50.0 nmol/L). These associations were strongest among men at risk of vitamin D deficiency [adjusted odds ratio for the lowest quartile of gait speed = 3.24; 95% CI: 1.56-6.73 and for the lowest quartile of hand grip strength = 3.28; 95% CI: 1.47-7.31] than in women at risk of vitamin D deficiency [adjusted odds ratio for the lowest quartile of gait speed = 2.72; 95% CI: 1.37-5.41 and for the lowest quartile of hand grip strength = 1.56; 95% CI: 0.81-3.00]. In conclusion, in older adults, particularly in men, the risk of vitamin D deficiency was directly associated with the lowest values of gait speed and of hand grip strength. However, randomized controlled trials are needed to overcome the possibility of reverse causation and residual confounding. Present results emphasise the need for strategies to promote the reduction of the high prevalence of low vitamin D status among the Portuguese older adult population.

This study investigated the effect of the period of use and location of intraoral appliances on enamel surface loss. This randomized, single blind in situ study was conducted in 2 crossover phases based on the period of use, in which maxillary and mandibular appliances were simultaneously worn. Bovine enamel blocks (n = 120) were randomly divided among the studied groups by surface hardness. In each phase, fifteen volunteers used one maxillary appliance and two mandibular appliances for 5 days. Erosive challenge was performed 4X/day by immersion in 0.01 M HCL for 2 minutes. In the continuous phase, the intraoral appliances were worn for 20 hours. In the intermittent phase the appliances were worn for 8 hours and 30 minutes. Enamel loss was determined profilometrically. The discomfort of use of the appliances were evaluated in a questionnaire. Data were analyzed by two-way ANOVA/Tukey's test and chi-square test (p

BACKGROUND:Due to the high rate of antigenic variation of influenza virus, seasonal characterization of the virus is crucial to assess and monitor the emergence of new pathogenic variants and hence formulate effective control measures. However, no study has yet been conducted in Mozambique to assess genetic, antigenic and antiviral susceptibility profile of influenza virus. METHODS:A subset of samples (n = 20) from influenza positive children detected in two hospitals in Maputo city during 2015 season as part of the implementation of influenza surveillance system, were selected. The following assays were performed on these samples: antigenic characterization by hemagglutination inhibition assay, genetic characterization by Sanger sequencing of hemagglutinin (HA) and neuraminidase (NA) and susceptibility to oseltamivir and zanamivir (NA inhibitors) by enzymatic assay. RESULTS:The A(H1N1)pdm09 subtype viruses remained closely related antigenically and genetically to the 2016 vaccine virus A/California/7/2009 and other widely distributed viruses belonging to genetic group 6B. The majority of influenza A(H3N2) viruses studied were antigenically similar to the 2016-2017 vaccine virus, A/Hong Kong/4801/2014, and their HA and NA gene sequences fell into genetic subclade 3C.2a being closely related to viruses circulating in southern Africa. The influenza B viruses were antigenically similar to the 2016 season vaccine virus and HA sequences of all three fell into the B/Yamagata-lineage, clade 3, but contained NA genes of the B/Victoria-lineage. All tested viruses were sensitive to oseltamivir and zanamivir. CONCLUSION:Overall, all Mozambican influenza A and B viruses were most closely related to Southern African viruses and all were sensitive to oseltamivir and zanamivir. These findings suggest the existence of an ecological niche of influenza viruses within the region and hence highlighting the need for joint epidemiologic and virologic surveillance to monitor the evolution of influenza viruses.