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Abstract Neutrophils (PMNs) are key players of innate immune responses through the release of cytoplasmic granule content and the formation of neutrophil extracellular traps (NETs). RNASET2 is an acidic ribonuclease, recently proposed as an alarmin signal associated with inflammatory responses. Here we show that, along the neutrophil maturation cascade, RNASET2 is expressed in segmented and mature PMNs. In human PMNs, RNASET2 colocalized with primary and tertiary granules and was found to be associated with NETs following PMA or Nigericin stimulation. Similarly, activation of PMNs by soluble immune complexes, a hallmark of several autoimmune diseases, also induced RNASET2-associated NETs. Genome-wide association studies recently identified RNASET2 among a cluster of genes associated with increased susceptibility to develop autoimmune diseases, including rheumatoid arthritis (RA). RNASET2 was found expressed by PMNs and macrophages infiltrating inflamed joints in a murine model of RA (K/BxN Serum-Transfer-Induced Arthritis, STIA), by immunostaining. Similar results were found in synovial biopsies of RA patients with active disease. In addition, we demonstrate that RNASET2 circulating levels correlated with the onset and the severity of disease in two mouse models of inflammatory arthritis, STIA and CIA (Collagen-Induced Arthritis) and in serum of RA patients. These results show that PMNs are an important source of RNASET2 and that its circulating levels are associated with RA development suggesting a role for RNASET2 in the pathogenesis of immune-mediated diseases.

Abstract Chemical Short-Range Order (CSRO) has attracted recent attention from many researchers, creating intense debates about its impact on material properties. The challenges lie in confirming and quantifying CSRO, as its detection proves exceptionally demanding, contributing to conflicting data in the literature regarding its true effects on mechanical properties. Our work uses high-precision calorimetric data to unambiguously prove the existence and, coupled with atomistic simulations, quantify the type of CSRO. This methodology allows us to propose a mechanism for its formation and destruction based on the heat evolution during thermal analysis and facilitates a precise identification of local ordering in CoCrNi alloys. Samples of CoCrNi (Co33Cr33Ni33) and CrNi2 (Cr33Ni66) alloys are fabricated in varying ordered states, extensively characterized via synchrotron X-ray diffraction, X-ray absorption spectroscopy, and transmission electron microscopy. Samples with considerably different ordered states are submitted to tensile tests with in-situ synchrotron X-ray diffraction. We demonstrate, despite inducing varied CSRO levels in CoCrNi, no significant alterations in overall mechanical behavior emerge. However, the CrNi2 alloy, which undergoes long-range ordering, experiences significant shifts in yield strength, ultimate tensile stress and ductility.

A systematic review (SR) is a research method for synthesizing evidence on a specific topic. Among the various types of systematic reviews, there are SRs of guidelines (CPGs) and SRs of SRs. Traditionally, they are limited to just one type of secondary evidence. This paper introduces an innovative SR methodology that combines CPGs and SRs to improve evidence synthesis and overcome the limitations of isolated use.Essential steps that should always precede the actual research process include registering the research protocol, formulating research questions and setting inclusion/exclusion criteria. Using the PRISMA protocol for comprehensive database searches, it's crucial to combine keywords with boolean operators and remove duplicates. The eligibility of studies should be assessed by selecting potentially relevant articles through an initial screening of titles and abstracts, followed by a meticulous analysis of the full-texts. Rigorous evidence evaluation tools, such as AGREE II for CPGs and AMSTAR 2 for SRs, and the double reviewer approach ensure high-quality selections. Additionally, converting summarized results into percentages and applying statistical analyses facilitate interpretation and improve the reliability of rater assessments. A further characteristic of this methodology is its adaptability to the evolution of healthcare research.

Actions to strengthen climate resilience are gaining more traction. In order to ensure effective adaptation, it is important to monitor the outcomes and impacts of these actions. However, there are numerous challenges and a multitude of approaches when it comes to monitoring adaptation to climate change. This paper addresses challenges in setting up mechanisms for monitoring climate resilience and adaptation projects. Drawing from three EU Horizon 2020 projects under the EU Mission on Adaptation to Climate Change, it synthesizes challenges and insights to support future initiatives in their monitoring endeavors for other projects to learn from. Findings, acquired through workshops with experts who shared learnings and challenges, highlight four key themes: the challenge of tailoring global frameworks to local needs, data availability and evaluation of data, interdisciplinary collaboration in monitoring, and stakeholder engagement for monitoring endeavors.

ObjectiveThis scoping review aimed to map existing research on adverse events encountered during telerehabilitation delivery, across rehabilitation populations. This includes identifying characteristics of adverse events (frequency/physical/non-physical, relatedness, severity) and examining adverse events by different modes of telerehabilitation delivery and disease states.IntroductionTelerehabilitation, a subset of telemedicine, has gained traction during the COVID-19 pandemic for remote service delivery. However, no prior scoping review, systematic review, or meta-analysis has identified and summarized the current primary research on adverse events in telerehabilitation. Understanding adverse events, such as falls during physiotherapy or aspiration pneumonia during speech therapy, is crucial for identifying limitations and optimizing delivery through risk mitigation and quality indicators. This understanding could also help to improve the uptake of telerehabilitation among clinicians and patients. This review addresses this gap by summarizing published literature on adverse events during telerehabilitation.MethodsThe review followed the Joanna Briggs Institute framework and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. The review protocol was registered and published on Open Science Framework. A comprehensive search across multiple databases (MEDLINE ALL/EMBASE/APA PsycINFO/CENTRAL/CINAHL) was conducted. Screening, extraction, and synthesis were performed in duplicate and independently. Data extraction followed the Template for Intervention Description and Replication framework and also involved extraction on authors, publication year (pre- or post-COVID), population, sample size, and modes of telerehabilitation delivery (asynchronous, synchronous, hybrid). For synthesis, data were summarized quantitatively using numerical counts and qualitatively via content analysis. The data were grouped by intervention type and by type of adverse event.Inclusion criteriaThis scoping review included qualitative and quantitative studies published between 2013-2023, written in English, and conducted in any geographic area. All modes of telerehabilitation delivery were included. Systematic reviews, meta-analyses, commentaries, protocols, opinion pieces, conference abstracts, and case series with fewer than five participants were excluded.ResultsThe search identified 11,863 references, and 81 studies were included in this review with a total of 3,057 participants (mean age:59.3 years; females:44.6%). Modes of telerehabilitation delivery (whether asynchronous, synchronous or hybrid) used in the studies included videoconferencing (52), phone calls (25), text messaging (4), email (6), mobile apps (10), and internet-based virtual reality systems (3). A total of 295 adverse events occurred during 84,534 sessions (0.3%), with the majority being physical (e.g., falls or musculoskeletal pain), non-serious/non-severe/mild, and unrelated to (i.e., not caused by) to the telerehabilitation provided.ConclusionsFrom the 81 included studies, telerehabilitation was delivered with related adverse events being rare, and mostly characterized as mild/non-severe. A comparable occurrence of adverse events (~30%) was found between asynchronous and synchronous telerehabilitation studies. When categorized by disease type, cardiac telerehabilitation studies had the most frequent adverse events. Detailed reporting of telerehabilitation interventions and adverse event characteristics is recommended for future studies (i.e., use of TIDieR reporting guidelines). Telerehabilitation has the potential to make rehabilitation services more accessible to patients; however, more evidence on the safety of telerehabilitation is needed.

ObjectiveThis scoping review aims to map the existing research on adverse events during the delivery of telerehabilitation.IntroductionTelerehabilitation, a subset of telemedicine, has gained traction during the COVID-19 pandemic as a means to deliver rehabilitation services remotely. However, there exists a research gap as there has yet to be any scoping review, systematic review, or meta-analysis published to identify and summarize the current primary research on adverse events related to telerehabilitation as a whole. It is important to understand how adverse events, such as falls during physiotherapy or aspiration pneumonia during speech language pathology sessions, are associated with telerehabilitation delivery. This will help to identify key limitations for optimizing telerehabilitation delivery by allowing for the development of key risk-mitigation measures and quality indicators. It can also help improve the uptake of telerehabilitation among clinicians and patients. This review aims to fill this research gap by conducting a search of published literature on adverse events in telerehabilitation. Anticipated key findings of this scoping review include identifying the characteristics and frequencies of adverse events during telerehabilitation, the patient populations and types of telerehabilitation associated with the most adverse events, and the quality of reporting of adverse events.MethodsThe review follows the Joanna Briggs Institute (JBI) methodological framework and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. The review protocol has been registered and published on Open Science Framework. A comprehensive search strategy was implemented across multiple databases (MEDLINE ALL, EMBASE, APA PsycINFO, CENTRAL, and CINAHL). All stages (screening, extraction, and synthesis) will be conducted in duplicate and independently, with data extraction following the TIDieR framework, along with authors, year of publication (before or after COVID), population and sample size, and specific mode/s of telerehabilitation delivery. For synthesis, data will be summarized quantitatively using numerical counts and qualitatively via content analysis. The data will be grouped by intervention type and by type of adverse event.Inclusion criteriaThis scoping review will include qualitative and quantitative studies published between 2013 and 2023, written in English, and conducted in any geographic area. All modes of telerehabilitation delivery (asynchronous, synchronous, or hybrid) will be included. Systematic reviews, meta-analyses, commentaries, protocols, opinion pieces, conference abstracts, and case series with fewer than five participants will be excluded.

The advancement of the mobile app market is reshaping healthcare, emphasizing the imperative for quality and efficacy in health applications. This methodology has been devised to assess mobile health applications, aiming to assist healthcare professionals in selecting apps for e-healthcare consumers. Key facets of this approach are: • A stringent selection process within mobile app stores • A standardized assessment using the Mobile App Rating Scale to achieve consistent and replicable evaluations, systematically organizing app evaluations • A comprehensive framework guiding healthcare practitioners in determining which apps to integrate into clinical practice and which to excludeCentral to this method is the emphasis on distinguishing apps that enhance clinical practice from those that fall short in important areas such as the effectiveness of proposed health features, data accuracy, adherence to clinical guidelines, data security, and user privacy. With heightened attention to usability and accessibility, the methodology also addresses the common risks inherent in mHealth implementation, ensuring that selected apps not only meet technical criteria but also align with the broader healthcare ecosystem's needs and challenges.

Abstract Left ventricular hypertrophy is a risk factor for cardiovascular mortality in patients on peritoneal dialysis (PD). Because icodextrin has a greater ultrafiltration power compared with glucose-based solutions for long dwell, it could improve left ventricular mass by reducing fluid overload. This was a randomized clinical trial that included patients on PD recruited from 2 teaching hospitals, in Sao Paulo—Brazil. Patients were allocated to the control glucose group (GLU) or the intervention icodextrin (ICO) group. Clinical and cardiac magnetic resonance image (MRI) parameters were evaluated at baseline and 6 months after randomization. The primary outcome was the change in left ventricular mass adjusted by surface area (ΔLVMI), measured by cardiac MRI. A total of 22 patients completed the study (GLU, N = 12 and ICO, N = 10). Baseline characteristics such as age, sex, underlying disease, and time on dialysis were similar in both groups. At baseline, 17 patients (77.3%) presented with left ventricular hypertrophy with no difference between groups (p = 0.748). According to the total body water (TBW)/extracellular water (ECW) ratio, 36.8% and 80% of patients from GLU and ICO groups, respectively, were considered hypervolemic (p = 0.044). During follow-up, ΔLVMI was 3.9 g/m (− 10.7, 2.2) in GLU and 5.2 (− 26.8, 16.8) in ICO group (p = 0.651). ΔLVMI correlated with change in brain natriuretic peptide (r = 0.566, p = 0.044), which remained significant in a multiple regression analysis. The use of the icodextrin-based solution in prevalent patients on PD compared with a glucose-based solution was not able to improve LMV. A larger randomized trial with a longer follow-up period may be needed to show changes in LVM in this patient population. Trial registration: this study has been registered at ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification #RBR-2mzhmj2, available at: https://ensaiosclinicos.gov.br/pesquisador .

The Socotra Archipelago (Yemen), a group of four islands off the north-eastern tip of Africa in the western Indian Ocean, has a population that relies heavily on small-scale fishing for livelihoods and food security. However, the reporting of fisheries catches by Yemen has consistently been incomplete, with artisanal (small-scale, commercial) catches underreported and small-scale non-commercial subsistence and recreational catches not reported at all. Here, we reconstruct the total small-scale catches and fishing effort from the waters of the Socotra Archipelago for 1950 to 2019, and derive catch-per-unit-effort (CPUE) estimates for these fisheries. The catch officially reported by the Food and Agriculture Organization on behalf of Yemen that was assumed taken from the archipelago is thought to be around 20% of the total reconstructed catch for the archipelago. The reconstructed small-scale catch increased from ~1,500 t in 1950 to an all-time peak of 12,000 t in 2000 before declining to 3,300 t by 2014. Thereafter, catches increased again slightly to just over 3,700 t·year-1 by 2019. Artisanal catches accounted for around 70% of total small-scale catches prior to 2010, but made up only around 46% by 2019. Conversely, subsistence catches increased from ~1,000 t in 2010 to ~2,000 t in 2019, and accounted for 54% of total catches by 2019. Small-scale fishing effort increased by over 1000% since 1950 and reached over 11 million kWdays by 2019. The CPUE derived for small-scale fisheries declined by 78% since 1950, from 1.4 kg·kWday-1 to 0.3 kg·kWday-1 in 2019, with most of the decline occurring after 2000. Our findings suggest resource overexploitation, and may assist efforts to more sustainably manage the Socotra Archipelago’s fish stocks. Small-scale fisheries support food and nutrient security of the local population, not least during political and humanitarian crises such as in Yemen.

Abstract With highly active anti-retroviral therapy (HAART), higher incidence of airway abnormalities is common in the HIV population consistent with the concept of accelerated lung “aging”. Our previous findings demonstrated that HIV induces human airway basal cells (BC) into destructive and inflammatory phenotypes. Since BC function as stem/progenitor cells of the small airway epithelium (SAE), responsible for self-renewal and differentiation of SAE, we hypothesized that BC from people living with HIV (PLWH) may have altered differentiation capacity that contribute to premature aging. The data demonstrates that BC from PLWH have impaired capacity to differentiate in vitro and senescent phenotypes including shortened telomeres, increased expression of β-galactosidase and cell cycle inhibitors, and mitochondrial dysfunction. In vitro studies demonstrated that BC senescence is partly due to adverse effects of HAART on BC. These findings provide an explanation for higher incidence of airway dysfunction and accelerated lung aging observed in PLWH.

Gender affects all aspects of life, and the working and learning environments of science, technology, engineering and geosciences present no exception. Gender issues concerning the access, permanence and ascension of women in exact sciences and Earth sciences careers in general are related to a variety of causes. The underrepresentation of women in science communications, sexual or moral harassment caused by professors and colleagues during undergraduate and graduate ages or the overloading of girls, when compared to boys, with housework during early school ages are some examples mentioned in the literature. In other words, the gender imbalance in science and technology careers may be seen as the result of a series of structured oppression suffered by women of all ages. In this context, we propose the development of an education package that is designed to understand these processes at different levels. One of the tools of this package is known as the “Theatre of the Oppressed”. Elaborated on by Augusto Boal in the 1970s, the Theatre of the Oppressed uses theatre techniques as a means of promoting social and political changes. Usually, a scene takes place that reveals a situation of oppression. The audience become what is called “spect-actors”, where they become active by exploring, showing and transforming the reality in which they are living. In the context of gender issues in exact sciences careers, the students can stage situations that reveal the subtle actions of power relations that usually put women in subservient positions. Our experience showed that, even though the acting is based on fiction, the spectators learn a great deal from the enactment because the simulation of real-life situations, problems and solutions stimulates the practice of resisting oppression in reality from within a setting that offers a safe space to practise making a change.

Abstract Time-Of-Flight (TOF) methods are very effective to detect particles accelerated in laser-plasma interactions, but they show significant limitations when used in experiments with high energy and intensity lasers, where both high-energy ions and remarkable levels of ElectroMagnetic Pulses (EMPs) in the radiofrequency-microwave range are generated. Here we describe a novel advanced diagnostic method for the characterization of protons accelerated by intense matter interactions with high-energy and high-intensity ultra-short laser pulses up to the femtosecond and even future attosecond range. The method employs a stacked diamond detector structure and the TOF technique, featuring high sensitivity, high resolution, high radiation hardness and high signal-to-noise ratio in environments heavily affected by remarkable EMP fields. A detailed study on the use, the optimization and the properties of a single module of the stack is here described for an experiment where a fast diamond detector is employed in an highly EMP-polluted environment. Accurate calibrated spectra of accelerated protons are presented from an experiment with the femtosecond Flame laser (beyond 100 TW power and ~ 1019 W/cm2 intensity) interacting with thin foil targets. The results can be readily applied to the case of complex stack configurations and to more general experimental conditions.

The effects of fishing have been documented across coral reefs worldwide. No-take marine reserves do not only act as a conservation tool but also allow an opportunity to study impacts of fishing, by acting as control sites. In addition, well-planned and well-managed no-take marine reserves (NTRs) provide conservation benefits that are essential to marine biodiversity and ecosystem-based management. The Abrolhos Marine National Park, off the tropical Brazilian coast, protects part of the largest coral reef system in the South Atlantic. To investigate the effects of fishing on reef fish richness, abundance, biomass, and functional diversity of the fish assemblage, we compared sites across two protection levels considering the variation in habitats (Fringing Reefs—Protected; Pinnacles Reefs—Protected; and Coastal Reefs—Open Access), using Baited Remote Underwater Stereo-Video systems (stereo-BRUVs). We adjusted generalized additive mixed models of fish assemblage characteristics with protection levels and environmental variables, such as topographic complexity (mean relief and relief variation), visibility, and benthic cover percentage. Inside NTRs, we found higher total biomass and biomass of fishery target species and carnivores, specifically for the Carcharhinidae (sharks) and Epinephelidae (groupers) families, indicating direct fisheries effects on these groups. In contrast, the ecological parameters of non-target fish were positively correlated with habitat characteristics, including mean relief and variance of relief. Moreover, fish functional diversity was higher within NTRs, demonstrating an even distribution of functional entities. The presence of large mobile predators and the overall higher biomass of carnivores inside the NTR indicate the effect of fishing exclusion. Our results point to the value of NTRs to study the effects of fishing and achieve biodiversity conservation and suggest the importance of using remote sampling methods to assess large mobile predators.

The discovery and characterization of layered intrusions around the globe have been predicated to a large degree on the imaging capabilities of the reflection seismic method. The ability of this tool to detect mineralization zones and structural controls such as faults and folds has been critical in unlocking the economic potential of igneous complexes, most notably the Bushveld Complex in South Africa. In this study, we present novel seismic constraints on the lesser-known Trompsburg Complex in South Africa. Two yet-unpublished seismic profiles were conducted end-to-end in the early 1990s, with a southwest-to-northeast trend through the centre of the ∼2,400 km2 Trompsberg potential field anomaly in South Africa, attributed to a 1915 ± 6 Ma buried layered intrusion complex. The complex was first detected by magnetic and gravity measurements near the town of Trompsburg in 1939 and was subsequently confirmed as a layered intrusion by borehole cores drilled thereafter. The combined length of the two profiles is 108 km. Both profiles have been reprocessed and interpreted to further constrain the subsurface expanse of the Trompsberg Complex along the seismic traverse. Processing and interpretation of the seismic profiles were aided by a handful of studies found in the literature: stratigraphy and physical property measurements of borehole cores that were drilled into the complex in the 1940s; pre-Karoo (∼317 Ma) lithological maps that were constructed based on boreholes in and around the investigation area; and potential field maps of the intrusion area near the town of Trompsburg. Most of the seismic reflection energy is concentrated within the top 1 km in both profiles, where localized reflectors with strong amplitudes are observed, due likely to the dolerite sills that permeate the Karoo cover. These sills obstruct seismic illumination of underlying structures due to their high acoustic impedance contrast with the surrounding soft rock sediments, rendering underlying reflections challenging to identify and enhance. The base of the Karoo is confidently identified to be at an average depth of 1.5 km and several reflection packages have been identified thereunder. These are linked to Proterozoic supracrustals associated with the Witwatersrand, Ventersdorp, Transvaal/Griqualand West, and Kheis Supergroups, as well as the Trompsburg Complex that intruded into them. The geometry of the Trompsburg Complex along the seismic traverse has been constrained with a moderate degree of confidence. It comprises a series of 30° northeasterly dipping reflectors near its southwestern boundary, flat reflectors near its centre at the town of Trompsburg, and 45° southwesterly dipping reflectors near its northeastern boundary. The lateral sub-Karoo extent of the complex is 60 km and its total thickness is difficult to constrain due to lack of deep reflections, but is likely between 6.6 and 7.5 km. The complex subcrops against the Karoo cover except near the southwestern region, where it is overlaid by Waterberg Group sediments.

Background Non-condensable gases (NCGs) are all gases that do not undergo liquefaction during the saturated steam sterilization process. During a sterilization cycle, the NCGs presence inside the chamber is one of the biggest threats to the sterilization process compromising process validation and product quality. Methods In this work, 170 testing of NCGs concentrations performed between September 2016 and August 2021 were carried out by Orionce Serviços de Metrologia Ltda (Barueri, SP, Brazil), according to EN285:2015 procedure. For steam generation, the types of water used were softened water (SW), one-step reverse osmosis (RO), purified water (PW), and water for injection (WFI). The data obtained were analyzed using Minitab® software, version 18.1, to identify a relationship between the water quality used for steam generation and the concentration of non-condensable gases determined into equipment qualification. Findings From total tests performed, 109 tests passed, and 61 tests failed, representing 64.2% and 35.8%, respectively. A higher failure rate was observed in terms of concentration of non-condensable gases in systems that used purified water for steam generation (64.7%), followed by softened water (55.6%), one-step reverse osmosis (42.9%), and water for injection (7.6%). Conclusion System processes using WFI for steam generation showed better results for steam quality approvement, in terms of NCGs concentration, compared to softened, purified, or reverse osmosis water treatments in the concentration of non-condensable gases in steam used for sterilization processes of industrial utilities.

Women with rheumatoid arthritis (RA) may carry an increased risk of adverse pregnancy outcomes (APO). The aims of this study were to compare pregnancy outcomes in RA patients as compared to the general obstetric population (GOP) and to identify a risk profile in RA. A case-control study was conducted on 82 prospectively followed pregnancies in RA and 299 pregnancies from the GOP. The mean age at conception was 31.50 ± 4.5 years, with a mean disease duration of 8.96 ± 6.3 years. The frequency of APO in RA patients was 41.5%, 18.3% experienced spontaneous abortions, 11.0% underwent preterm deliveries, 7.3% had small for gestational age infants, 4.9% experienced intrauterine growth restriction, 1.2% experienced stillbirth, and 1.2% suffered from eclampsia. The risk of APO was correlated with a maternal age higher than 35 years (p = 0.028, OR = 5.59). The rate of planned pregnancies was 76.8%, and the subfertility rate was 4.9%. Disease activity improved every trimester, and approximately 20% experienced an improvement in the second trimester. Planned pregnancies and corticosteroids use (≤10 mg daily) were protective factors for APO in RA pregnancies (p < 0.001, OR = 0.12, p = 0.016, OR = 0.19, respectively). There was no significant association between APO and disease activity or DMARDs used before and during pregnancy. Regarding the comparison between the RA group and the controls, RA mothers were significantly older (p = 0.001), had shorter pregnancies (p < 0.001), and had neonates with a lower birth weight (p < 0.001).

In Brazil, although access to education is guaranteed by law, the inclusion of disabled people in the educational system is not occurring at the necessary speed, either due to lack of educational resources or lack of adequate training of educators. The extension project Democratization of the teaching of morphological sciences: promoting accessibility for visually impaired people aims to research and develop adequate didactic material, low of cost, and easy to reproduce, for the teaching of cellular biology and histology to the visually impaired. The tactile matrices, forms of representing structures with the use of materials with different textures and reliefs, were the didactic tools chosen. At present, tactile matrices of various cells of biological tissues are being made and tested. The results obtained will be published with the confection of an atlas of morphology and the creation of the electronic website of the project.

Abstract The Colombian Biogeographic Choco (CBC) and the La Plata Basin (LPB) are regions with high biodiversity. However, these areas are characterized by scarce climatological information, complex orography, and rain-gauge network unevenly distributed. Interpolated data from the ground station might overcome these aspects. For this reason, is necessary to identify the best technique for the spatial interpolation of rainfall. Hence, the spatial interpolation techniques were applied to annual and seasonal rainfall in the CBC and LPB. Geostatistical results and deterministic approaches were compared by cross-validation. Cokriging with spherical (gaussian) model is the best interpolator in the CBC (LPB), as indicated by the lowest root mean square error (RMSE) and a standardized RMSE close to one. The CBC shows three rainfall cores: the northern, 9,000 mm/year; the central-southern, 10,000 mm/year; and the southern, 7,000 mm/year. The LPB shows a west-east rainfall gradient, with a minimum to the west (450 mm/year) and a maximum in the mid-west (2,000 mm/year). To the north of the LPB, rainfall reaches 1,500 mm/year, while in the south it reaches only 900 mm/year. The results in our study may be useful for scientists and decision-makers for use in environmental and hydrological models for the CBC and the LPB.

Abstract Background and purpose Faced with decades of severe economic decline, the city of Detroit, Michigan (USA) is on the cusp or reinventing itself. A Consortium was formed of three higher education institutions that have an established mission to serve an urban population and a vested interest in the revitalization of the health, welfare, and economic opportunity in the Detroit metro region that is synergistic with national goals to diversify the biomedical workforce. The purpose of this article is to describe the rationale, approach, and model of the Research Enhancement for BUILDing Detroit (ReBUILDetroit) Consortium, as a cross-campus collaborative for students, faculty, and institutional development. The ReBUILDetroit program is designed to transform the culture of higher education in Detroit, Michigan by educating and training students from diverse and socio-economically disadvantaged backgrounds to become the next generation of biomedical researchers. Key program highlights Marygrove College, University of Detroit Mercy, and Wayne State University established a Consortium to create and implement innovative, evidence-based and cutting-edge programming. Specific elements include: (1) a pre-college summer enrichment experience; (2) an inter-institutional curricular re-design of target foundational courses in biology, chemistry and social science using the Research Coordination Network (RCN) model; and (3) cross-institutional summer faculty-mentored research projects for ReBUILDetroit Scholars starting as rising sophomores. Student success support includes intentional and intrusive mentoring, financial support, close faculty engagement, ongoing workshops to overcome academic and non-academic barriers, and cohort building activities across the Consortium. Institutional supports, integral to program creation and sustainability, include creating faculty learning communities grounded in professional development opportunities in pedagogy, research and mentorship, and developing novel partnerships and accelerated pipeline programming across the Consortium. This article highlights the development, implementation and evolution of high-impact practices critical for student learning, research-based course development, and the creation of inter-institutional learning communities as a direct result of ReBUILDetroit. Implications Our cross-institutional collaboration and leveraging of resources in a difficult economic environment, drawing students from high schools with a myriad of strengths and challenges, serves as a model for higher education institutions in large, urban centers who are seeking to diversify their workforces and provide additional opportunities for upward mobility among diverse populations.

Abstract Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.

Abstract Although clean and abundant water is the keystone of thriving communities, increasing demand and volatile climate patterns are depleting rivers and aquifers. Moreover, the quality of such water sources is threatened by noxious contaminants, of which heavy metals represents an area of growing concern. Recently, graphene oxide (GO) has been suggested as an adsorbent; however, a support is desirable to ensure a high surface area and an immobile phase. Herein, we described the preparation and characterization of a supported-epoxidized carbon nanotube (SENT) via the growth of multi walled carbon nanotubes (MWNTs) onto a quartz substrate. Subsequent epoxidation provides sufficient functionality to enable adsorbent of heavy metals (Cd2+, Co2+, Cu2+, Hg2+, Ni2+, and Pb2+) from aqueous solution with initial concentrations (60–6000 ppm) chosen to simulate high industrial wastewater contamination. The SENT adsorption efficiency is >99.4% for all metals and the saturation concentration is significantly greater than observed for either GO or acid treated MWNTs. The SENT adsorbent may be readily regenerated under mild conditions using a globally available household chemical, vinegar. 1 g of SENT has the potential to treat 83,000 L of contaminated water down to WHO limits which would be sufficient for 11,000 people.

Bell’s theorem has important implications for quantum information processing. Here the authors experimentally investigate the violation of a Bell-like inequality in the case of distant parties whose correlations are mediated by independent sources, a realistic feature in future quantum networks.

INTRODUCTION:Brazil ranks second in the absolute number of transplantations in the world. Despite improvements in graft survival, many patients will progress to graft loss and return to dialysis. Concerns exist regarding adverse clinical outcomes in this population when undergone peritoneal dialysis (PD). OBJECTIVE:To compare the occurrence of mortality, technique failure, and peritonitis among incident patients in PD coming from either Tx or pre-dialysis treatment. METHODOLOGY:A retrospective study in which 47 adult patients with Tx failure (Tx group) were matched for age, gender, diabetes mellitus (DM), modality and start year of PD, with 1:1 predialysis patient (nTx group). The Fine-Gray competing risk model was used to analyze mortality and technique failure. RESULTS:Compared to nTx, the Tx group had a lower body mass index, serum potassium, and albumin concentrations. A higher ferritin level, transferrin saturation and the number of patients with positive serology for viral hepatitis were also observed in the Tx group. In the multivariate analysis, patients of the Tx group had 4.4-times higher risk of death (p = 0.007), with infection as the main cause. Technique failure and peritonitis were similar in both groups. CONCLUSION:Previous Tx is a risk factor for mortality but not for technique failure or peritonitis in incident patients on a PD program.

Rotator cuff tear is a common orthopedic condition. Metalloproteinases (MMP) and their inhibitors (TIMP) seem to play a role in the development of joint injuries and in the failure of tissue healing. However, the mechanisms of regulation of gene expression in tendons are still unknown. Epigenetic mechanisms, such as DNA methylation and microRNAs regulation, are involved in the dynamic control of gene expression. Here, the mRNA expression and DNA methylation status of MMPs (MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14) and TIMPs (TIMP1-3) and the expression of miR-29 family members in ruptured supraspinatus tendons were compared with non-injured tendons of individuals without this lesion. Additionally, the gene expression and methylation status at the edge of the ruptured tendon were compared with macroscopically non-injured rotator cuff tendon samples from the anterior and posterior regions of patients with tendon tears. Moreover, the possible associations between the molecular alterations and the clinical and histologic characteristics were investigated. Dysregulated expression and DNA methylation of MMP and TIMP genes were found across the rotator cuff tendon samples of patients with supraspinatus tears. These alterations were influenced at least in part by age at surgery, sex, smoking habit, tear size, and duration of symptoms. Alterations in the studied MMP and TIMP genes may contribute to the presence of microcysts, fissures, necrosis, and neovascularization in tendons and may thus be involved in the tendon healing process. In conclusion, MMPs and their inhibitors are regulated by epigenetic modifications and may play a role in rotator cuff tears.

Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27-39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p

O presente projeto extensionista montou e implantou uma coleção didática e de referência sobre lixo marinho, composta por recipientes de vidro transparente, contendo os itens de lixo marinho coletados, fichas numeradas, uma estante de aço e um fichário. A coleção foi exposta durante a Semana Nacional de Ciência e Tecnologia de 2013 e apresentada a alunos do ensino fundamental, cumprindo assim com os objetivos de disseminar o assunto para a sociedade, tratando-o de forma interdisciplinar.DOI: http://dx.doi.org/10.35700/ca.2015.ano2n3.p123-128.1767

Background: The therapeutic approach to chronic aspecific low back pain (CALBP) has to consider the multifactorial aetiology of the disorder. International guidelines do not agree on unequivocal treatment indications. Recommendations for fascial therapy are few and of low level evidence but several studies indicate strong correlations between fascial thickness and low back pain. This study aims at comparing the effectiveness of Fascial Manipulation® associated with a physiotherapy program following guidelines for CALBP compared to a physiotherapy program alone. Methods: 24 subjects were randomized into two groups, both received eight treatments over 4 weeks. Outcomes were measured at baseline, at the end of therapy and at a 1 month and a 3 months follow-up. Pain was measured with the visual analogue scale (VAS) and the brief pain inventory (BPI), function with the Rolland-Morris disability questionnaire (RMDQ), state of well-being with the short-form 36 health-survey (SF-36). The mean clinical important difference (MCID) was also measured. Results: Patients receiving Fascial Manipulation® showed statistically and clinically significant improvements at the end of care for all outcomes, in the short (RMDQ, VAS, BPI) and medium term for VAS and BPI compared to manual therapy. The MCID show significant improvements in the means and percentage of subjects in groups in all outcomes post-treatment, in the short and medium term. Conclusion: Fascial tissues were implicated in the aetiology of CALBP and treatment led to decreased symptomatic, improved functional and perceived well-being outcomes that were of greater amplitude compared to manual therapy alone.

It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers), but clusters of receptors (receptor mosaics), altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

Background: The therapeutic approach to chronic aspecific low back pain (CALBP) has to consider the multifactorial aetiology of the disorder. International guidelines do not agree on unequivocal treatment indications. Recommendations for fascial therapy are few and of low level evidence but several studies indicate strong correlations between fascial thickness and low back pain. This study aims at comparing the effectiveness of Fascial Manipulation® associated with a physiotherapy program following guidelines for CALBP compared to a physiotherapy program alone. Methods: 24 subjects were randomized into two groups, both received eight treatments over 4 weeks. Outcomes were measured at baseline, at the end of therapy and at a 1 month and a 3 months follow-up. Pain was measured with the visual analogue scale (VAS) and the brief pain inventory (BPI), function with the Rolland-Morris disability questionnaire (RMDQ), state of well-being with the short-form 36 health-survey (SF-36). The mean clinical important difference (MCID) was also measured. Results: Patients receiving Fascial Manipulation® showed statistically and clinically significant improvements at the end of care for all outcomes, in the short (RMDQ, VAS, BPI) and medium term for VAS and BPI compared to manual therapy. The MCID show significant improvements in the means and percentage of subjects in groups in all outcomes post-treatment, in the short and medium term. Conclusion: Fascial tissues were implicated in the aetiology of CALBP and treatment led to decreased symptomatic, improved functional and perceived well-being outcomes that were of greater amplitude compared to manual therapy alone.

Trypanosoma cruzi, the etiological agent of Chagas’ disease, occurs as different strains or isolates that may be grouped in two major phylogenetic lineages: T. cruzi I, associated with the sylvatic cycle and T. cruzi II, linked to the human disease. In the mammalian host the parasite has to invade cells and many studies implicated the flagellated trypomastigotes in this process. Several parasite surface components and some of host cell receptors with which they interact have been identified. Our work focused on how amastigotes, usually found growing in the cytoplasm, can invade mammalian cells with infectivities comparable to that of trypomastigotes. We found differences in cellular responses induced by amastigotes and trypomastigotes regarding cytoskeletal components and actin-rich projections. Extracellularly generated amastigotes of T. cruzi I strains may display greater infectivity than metacyclic trypomastigotes towards cultured cell lines as well as target cells that have modified expression of different classes of cellular components. Cultured host cells harboring the bacterium Coxiella burnetii allowed us to gain new insights into the trafficking properties of the different infective forms of T. cruzi, disclosing unexpected requirements for the parasite to transit between the parasitophorous vacuole to its final destination in the host cell cytoplasm.O agente etiológico da doença de Chagas, Trypanosoma cruzi, ocorre como cepas ou isolados que podem ser agrupados em duas grandes linhagens filogenéticas: T. cruzi I associada ao ciclo silvestre e T. cruzi II ligada à doençahumana. No hospedeiro mamífero o parasita tem que invadir células, e vários estudos relacionam as formas flageladas tripomastigotas neste processo. Diferentes componentes de superfície dos parasitas e alguns dos respectivos receptores foram identificados. Em nosso trabalho temos procurado compreender como amastigotas, que normalmente são encontrados crescendo no citoplasma, podem invadir células de mamíferos com infectividade comparável às dos tripomastigotas. Encontramos diferenças nas respostas celulares induzidas por amastigotas e tripomastigotas em relação a componentes de citoesqueleto e projeções de membrana ricas em actina. Amastigotas de cepas de T. cruzi I gerados extracelularmente, podem apresentar infectividade maior que tripomastigotas metacíclicos para linhagens celulares e células com expressão alterada em diferentes classes de componentes celulares. Células albergando a bactéria Coxiella burnetii tem nos permitido obter novos enfoques sobre as propriedades de tráfego intracelular das diferentes formas infectivas do T. cruzi, revelando requerimentos inesperados para o parasita transitar entre seu vacúolo parasitóforo até seu destino final no citoplasma da célula hospedeira.

The anterior cruciate ligament (ACL) is one of the most frequently injured structures during high-impact sporting activities. Gene expression analysis may be a useful tool for understanding ACL tears and healing failure. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has emerged as an effective method for such studies. However, this technique requires the use of suitable reference genes for data normalization. Here, we evaluated the suitability of six reference genes (18S, ACTB, B2M, GAPDH, HPRT1, and TBP) by using ACL samples of 39 individuals with ACL tears (20 with isolated ACL tears and 19 with ACL tear and combined meniscal injury) and of 13 controls. The stability of the candidate reference genes was determined by using the NormFinder, geNorm, BestKeeper DataAssist, and RefFinder software packages and the comparative ΔCt method. ACTB was the best single reference gene and ACTB+TBP was the best gene pair. The GenEx software showed that the accumulated standard deviation is reduced when a larger number of reference genes is used for gene expression normalization. However, the use of a single reference gene may not be suitable. To identify the optimal combination of reference genes, we evaluated the expression of FN1 and PLOD1. We observed that at least 3 reference genes should be used. ACTB+HPRT1+18S is the best trio for the analyses involving isolated ACL tears and controls. Conversely, ACTB+TBP+18S is the best trio for the analyses involving (1) injured ACL tears and controls, and (2) ACL tears of patients with meniscal tears and controls. Therefore, if the gene expression study aims to compare non-injured ACL, isolated ACL tears and ACL tears from patients with meniscal tear as three independent groups ACTB+TBP+18S+HPRT1 should be used. In conclusion, 3 or more genes should be used as reference genes for analysis of ACL samples of individuals with and without ACL tears.

Rotator cuff tear is one of the most common causes of shoulder dysfunction. Gene expression analysis may be a useful tool for understanding tendon tears and the failure of cuff healing, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) has become an effective method for such studies. However, this technique requires the use of suitable reference genes for data normalization. Here, we evaluate the suitability of six reference genes (18S, ACTB, B2M, GAPDH, HPRT1 and TBP) using samples from the rotator cuff tendons of 28 individuals with tendon tears (3 tendons regions) and 8 controls (2 tendon regions); for the tear patients, we evaluated ruptured and non-ruptured tendon samples. The stability of the candidate reference genes was determined using the NormFinder, geNorm, BestKeeper and DataAssist software packages. Overall, HPRT1 was the best single reference gene, and HPRT1+TBP composed the best pair and HPRT1+TBP+ACTB composed the best trio of reference genes from the analysis of different groups, including the simultaneous analysis of all tissue samples. To identify the optimal combination of reference genes, we evaluated the expression of COL1A1 and COL3A1, and no obvious differences were observed when using 2, 3 or 4 reference genes for most of the analyses. However, COL3A1 expression differed between ruptured and non-ruptured (posterior superior region) tendons of patients only when normalized by HPRT1+TBP+B2M and HPRT1+TBP. On the other hand, the comparison between these two groups using the best trio of reference genes (HPRT1+TBP+ACTB) and 4 reference genes did not revealed a significant difference in COL3A1 expression. Consequently, the use of suitable reference genes for a reliable gene expression evaluation by RT-qPCR should consider the type of tendon samples investigated. HPRT1+TBP+ACTB seems to be the best combination of reference genes for the analysis of involving different tendon samples of individuals with rotator cuff tears.

BCRP/ABCG2 emerged as an important multidrug resistance protein, because it confers resistance to several classes of cancer chemotherapeutic agents and to a number of novel molecularly-targeted therapeutics such as tyrosine kinase inhibitors. Gefitinib is an orally active, selective EGFR tyrosine kinase inhibitor used in the treatment of patients with advanced non small cell lung cancer (NSCLC) carrying activating EGFR mutations. Membrane transporters may affect the distribution and accumulation of gefitinib in tumour cells; in particular a reduced intracellular level of the drug may result from poor uptake, enhanced efflux or increased metabolism.The present study, performed in a panel of NSCLC cell lines expressing different ABCG2 plasma membrane levels, was designed to investigate the effect of the efflux transporter ABCG2 on intracellular gefitinib accumulation, by dissecting the contribution of uptake and efflux processes.Our findings indicate that gefitinib, in lung cancer cells, inhibits ABCG2 activity, as previously reported. In addition, we suggest that ABCG2 silencing or overexpression affects intracellular gefitinib content by modulating the uptake rather than the efflux. Similarly, overexpression of ABCG2 affected the expression of a number of drug transporters, altering the functional activities of nutrient and drug transport systems, in particular inhibiting MPP, glucose and glutamine uptake.Therefore, we conclude that gefitinib is an inhibitor but not a substrate for ABCG2 and that ABCG2 overexpression may modulate the expression and activity of other transporters involved in the uptake of different substrates into the cells.

The Cancer Genome Atlas (TCGA) microRNA (miRNA) initiative has revealed a pivotal role for miRNAs in cancer. Utilizing the TCGA raw data, we performed the first mapping of viral miRNA sequences within cancer and adjacent normal tissues. Results were integrated with TCGA RNA-seq to link the expression of viral miRNAs to the phenotype. Using clinical data and viral miRNA mapping results we also performed outcome analysis. Three lines of evidence lend credence to an active role of viral miRNAs in solid malignancies. First, expression of viral miRNA is consistently higher in cancerous compared to adjacent noncancerous tissues. Second, viral miRNA expression is associated with significantly worse clinical outcome among patients with early stage malignancy. These patients are also featured by increased expression of PD1/PD-L1, a pathway implicated in tumors escaping immune destruction. Finally, a particular cluster of EBV-miRNA (miR-BART2, miR-BART4, miR-BART5, miR-BART18, and miR-BART22) is associated with expression of cytokines known to inhibit host response to cancer. Quantification of specific viral miRNAs may help identify patients who are at risk of poor outcome. These patients may be candidates for novel therapeutic strategies incorporating antiviral agents and/or inhibitors of the PD-1/PD-L1 pathway.

To estimate the prevalence of one month psychotropic drug use in São Paulo, Brazil, and to assess the gap treatment between the presence of mental disorders and psychotropic drug users.A probabilistic sample of non-institutionalized individuals from the general population of São Paulo (n = 2336; turnout: 84.5%) who were 15 years or older were interviewed by a trained research staff, applying the Composite International Diagnostic Interview 2.1 (CIDI WHO) (depression, anxiety-phobia, OCD\PTSD, alcoholism sections), and an inventory investigating psychotropic drug use during the 12-month and one-month periods immediately preceding the interview. Logistic models were fitted to investigate associations between psychotropic drug use as well as socio-demographic and clinical variables.The one month prevalence of psychotropic drug use in São Paulo was 5.89%, the most commonly used drugs were antidepressants (3.15%) and tranquilizers (2.67%). A higher consumption of psychotropic drugs (overall, antidepressants and tranquilizers) was observed among women (OR:2.42), older individuals (OR:1.04), individuals with higher levels of formal education (1.06), and individuals with a family (OR:2.29) or personal history of mental illness (OR:3.27). The main psychotropic drug prescribers were psychiatrists (41%), followed by general practitioners (30%); 60% of psychotropic drugs were obtained through a government-run dispensing program. Most individuals who obtained a positive diagnosis on the CIDI 2.1 during the previous month were not using psychotropic medication (85%). Among individuals with a diagnosis of moderate to severe depression, 67.5% were not on any pharmacological treatment.There is a change in the type of psychotropic more often used in São Paulo, from benzodiazepines to antidepressants, this event is observed in different cultures. The prevalence of use is similar to other developing countries. Most of the patients presenting a psychiatric illness in the month prior to testing were not receiving any sort of psychiatric medication. This may be explained by a failure to identify cases in primary care, which could be improved (and access to treatment could be facilitated) if professionals received more specialized training in managing cases with mental health problems.

ObjectiveTo determine the prevalence of psychiatric disorders in the prison population in the State of São Paulo, Brazil.MethodsThrough stratified random sampling, 1.192 men and 617 women prisoners were evaluated for the presence of psychiatric disorders by the Composite International Diagnostic Interview, 2.1 version, according to definitions and criteria of International Classification of Diseases (ICD-10). The prevalence estimates of mental disorders and their respective 95% confidence intervals were calculated and adjusted for sample design through complex sample analysis.ResultsLifetime and 12-month prevalence rates differed between genders. Lifetime and 12-month prevalence of any mental disorder was, respectively, 68.9% and 39.2% among women, and 56.1% and 22.1% among men. Lifetime and 12-month prevalence of anxious-phobic disorders was, respectively, 50% and 27.7% among women and 35.3% and 13.6% among men, of affective disorders was 40% and 21% among women and 20.8% and 9.9% among men, and of drug-related disorders was 25.2% and 1.6% among women and 26.5% and 1.3% among men. For severe mental disorders (psychotic, bipolar disorders, and severe depression), the lifetime and 12-month prevalence rates were, respectively, 25.8% and 14.7% among women, and 12.3% and 6.3% among men.ConclusionsThis is the first large-scale epidemiological study performed with the prison population in Brazil, revealed high rates of psychiatric disorders among men and women. Many similarities, as well as some differences, were found between our results and those of studies conducted in other countries. The differences observed are more likely due to the peculiarities of the prison systems in each country than to the diagnostic criteria adopted in the studies. This fact reinforces the importance of conducting such studies as part of planning and development of appropriate policies for the particular mental health needs of specific prison populations.

BACKGROUND: Early life social adversity can influence stress response mechanisms and is associated with anxious behaviour and reductions in callosal area later in life. OBJECTIVE: To evaluate the association between perceptions of parental bonding in childhood/adolescence, hypothalamic-pituitary-adrenal (HPA) axis response, and callosal structural integrity in adult victims of severe urban violence with and without PTSD. METHODS: Seventy-one individuals with PTSD and 62 without the disorder were assessed with the Parental Bonding Instrument (PBI). The prednisolone suppression test was administered to assess cortisol levels, and magnetic resonance imaging was used to assess the total area of the corpus callosum (CC), as well as the areas of callosal subregions. RESULTS: The PBI items related to the perception of 'not having a controlling mother' (OR 4.84; 95%CI [2.26-10.3]; p=0.01), 'having a caring father' (OR 2.46; 95'%CI [1.18-5.12]; p=0.02), and 'not having controlling parents' (OR 2.70; 95%CI [1.10-6.63]; p=0.04) were associated with a lower risk of PTSD. The PTSD group showed a blunted response to the prednisolone suppression test, with lower salivary cortisol levels upon waking up (p=0.03). Individuals with PTSD had smaller total CC area than those without the disorder, but these differences were not statistically significant (e-value =0.34). CONCLUSIONS: Healthy parental bonding, characterized by the perception of low parental control and high affection, were associated with a lower risk of PTSD in adulthood, suggesting that emotional enrichment and the encouragement of autonomy are protective against PTSD in adulthood.

OBJECTIVE: To analyze the association between drug (DAD) and alcohol (AAD) abuse and dependency and criminal and clinical background by gender of prisoners in São Paulo, Brazil. METHOD: Cross-sectional study, random sample stratified by administrative district, from which prisons and prisoners were selected via random, multistage sampling. Psychiatric diagnoses were made with the CIDI 2.1. Lifetime prevalence and 95% CI were calculated and adjusted via analysis of complex samples. Multinomial logistic regression analysis was carried out with four categories of dependent variables: presence AAD; presence DAD; presence of another mental disorder; no mental disorders. For female alcohol and drug abuse and dependency (ADAD) were combined into a single category. RESULTS: The sample was composed by 1809 interviewed prisoners (1192 men and 617 women). Prevalence of DAD and AAD was 25.2% and 15.6%, respectively, among female prisoners, and 26.5% and 18.5% among males. Male prisoners with DAD were more likely to have a criminal record as an adolescent (OR 2.17), to be a repeat offender (OR 2.85), and to have committed a property crime (OR 2.18). Prisoners with AAD were repeat offenders (OR 2.18). Among female prisoners, ADAD was associated with repeat offenses (OR 3.39), a criminal record as an adolescent (OR 9.24), a clinical or infectious condition (OR 5.09), another health problem (OR 3.04), and violent crime (OR 2.5). CONCLUSION: The study confirmed an association between drug-use disorders and the criminal and clinical background in the study population. Prisoners with such disorders were more likely to be repeat offenders and to have a criminal record as adolescents. Among female prisoners disorders were also associated with violent crime and health problems, while among males they were associated with property crime. These patterns in clinical and criminal backgrounds illustrate the need for social rehabilitation programs and specific medical treatment for prison populations.

CRC cancer is one of the deadliest diseases in Western countries. In order to develop prognostic biomarkers for CRC (colorectal cancer) aggressiveness, we analyzed retrospectively 267 CRC patients via a novel, multidimensional biomarker platform. Using nanofluidic technology for qPCR analysis and quantitative fluorescent immunohistochemistry for protein analysis, we assessed 33 microRNAs, 124 mRNAs and 9 protein antigens. Analysis was conducted in each single dimension (microRNA, gene or protein) using both the multivariate Cox model and Kaplan-Meier method. Thereafter, we simplified the censored survival data into binary response data (aggressive vs. non aggressive cancer). Subsequently, we integrated the data into a diagnostic score using sliced inverse regression for sufficient dimension reduction. Accuracy was assessed using area under the receiver operating characteristic curve (AUC). Single dimension analysis led to the discovery of individual factors that were significant predictors of outcome. These included seven specific microRNAs, four genes, and one protein. When these factors were quantified individually as predictors of aggressive disease, the highest demonstrable area under the curve (AUC) was 0.68. By contrast, when all results from single dimensions were combined into integrated biomarkers, AUCs were dramatically increased with values approaching and even exceeding 0.9. Single dimension analysis generates statistically significant predictors, but their predictive strengths are suboptimal for clinical utility. A novel, multidimensional integrated approach overcomes these deficiencies. Newly derived integrated biomarkers have the potential to meaningfully guide the selection of therapeutic strategies for individual patients while elucidating molecular mechanisms driving disease progression.

Serous ovarian cancer (SEOC) is the deadliest gynecologic malignancy. MicroRNAs (miRNAs) are a class of small noncoding RNAs which regulate gene expression and protein translation. MiRNAs are also encoded by viruses with the intent of regulating their own genes and those of the infected cells. This is the first study assessing viral miRNAs in SEOC. MiRNAs sequencing data from 487 SEOC patients were downloaded from the TCGA website and analyzed through in-house sequencing pipeline. To cross-validate TCGA analysis, we measured the expression of miR-H25 by quantitative immunofluorescence in an additional cohort of 161 SEOC patients. Gene, miRNA expression, and cytotoxicity assay were performed on multiple ovarian cancer cell lines transfected with miR-H25 and miR-BART7. Outcome analysis was performed using multivariate Cox and Kaplan-Meier method. Viral miRNAs are more expressed in SEOC than in normal tissues. Moreover, Herpetic viral miRNAs (miR-BART7 from EBV and miR-H25 from HSV-2) are significant and predictive biomarkers of outcome in multivariate Cox analysis. MiR-BART7 correlates with resistance to first line chemotherapy and early death, whereas miR-H25 appears to impart a protective effect and long term survival. Integrated analysis of gene and viral miRNAs expression suggests that miR-BART7 induces directly cisplatin-resistance, while miR-H25 alters RNA processing and affects the expression of noxious human miRNAs such as miR-143. This is the first investigation linking viral miRNA expression to ovarian cancer outcome. Viral miRNAs can be useful to develop biomarkers for early diagnosis and as a potential therapeutic tool to reduce SEOC lethality.

Shoulder instability is a common shoulder injury, and patients present with plastic deformation of the glenohumeral capsule. Gene expression analysis may be a useful tool for increasing the general understanding of capsule deformation, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) has become an effective method for such studies. Although RT-qPCR is highly sensitive and specific, it requires the use of suitable reference genes for data normalization to guarantee meaningful and reproducible results. In the present study, we evaluated the suitability of a set of reference genes using samples from the glenohumeral capsules of individuals with and without shoulder instability. We analyzed the expression of six commonly used reference genes (ACTB, B2M, GAPDH, HPRT1, TBP and TFRC) in the antero-inferior, antero-superior and posterior portions of the glenohumeral capsules of cases and controls. The stability of the candidate reference gene expression was determined using four software packages: NormFinder, geNorm, BestKeeper and DataAssist. Overall, HPRT1 was the best single reference gene, and HPRT1 and B2M composed the best pair of reference genes from different analysis groups, including simultaneous analysis of all tissue samples. GenEx software was used to identify the optimal number of reference genes to be used for normalization and demonstrated that the accumulated standard deviation resulting from the use of 2 reference genes was similar to that resulting from the use of 3 or more reference genes. To identify the optimal combination of reference genes, we evaluated the expression of COL1A1. Although the use of different reference gene combinations yielded variable normalized quantities, the relative quantities within sample groups were similar and confirmed that no obvious differences were observed when using 2, 3 or 4 reference genes. Consequently, the use of 2 stable reference genes for normalization, especially HPRT1 and B2M, is a reliable method for evaluating gene expression by RT-qPCR.

BACKGROUND: Tonic Immobility is a temporary state of motor inhibition in situations involving extreme fear. The first scale developed for its assessment was the 10-item Tonic Immobility Scale (TIS). However, there are still few studies on its structural (dimensional) validity. The objective of this study was to reassess the factor structure of the TIS applied to representative samples exposed to general trauma of two Brazilian mega-cities. METHODS: The sample comprised 3,223 participants reporting at least one traumatic experience. In São Paulo (n = 2,148), a Confirmatory Factor Analysis (CFA) first tested the originally proposed two-dimensional structure. This was followed by sequential Exploratory Structural Equation Models to identify the best fitting model, and subsequently tested in Rio de Janeiro (n = 1,075) via CFA. Alternative reduced versions were further explored using the aggregate sample. Model-based Item Response Theory (IRT) location parameters were also investigated. RESULTS: An absence of factor-based convergent and discriminant validity rejected the original proposition. However, the one-dimensional structure still held several residual correlations. Further exploration indicated the sustainability of reduced versions with seven (alternative A) and six (alternative B) items. Both presented excellent fit and no relevant residual item correlation. According to the IRT location parameters, items in alternative B covered a wider range of the latent trait. The Loevinger's H scalability coefficients underscored this pattern. CONCLUSIONS: The original model did not hold. A one-factor solution was the most tenable in both large samples, but with significant item residual correlations, indicating that content redundancies persisted. Further reduced and simplified versions of the TIS proved promising. Although studies are yet to be carried out in other settings, it is the authors' impression that the restricted versions of the TIS are already apt for use in epidemiologic studies since the pros tend to outweigh the cons (as outlined in the Discussion section).

Bell's theorem was a cornerstone for our understanding of quantum theory and the establishment of Bell non-locality played a crucial role in the development of quantum information. Recently, its extension to complex networks has been attracting growing attention, but a deep characterization of quantum behavior is still missing for this novel context. In this work we analyze quantum correlations arising in the bilocality scenario, that is a tripartite quantum network where the correlations between the parties are mediated by two independent sources of states. First, we prove that non-bilocal correlations witnessed through a Bell-state measurement in the central node of the network form a subset of those obtainable by means of a local projective measurement. This leads us to derive the maximal violation of the bilocality inequality that can be achieved by arbitrary two-qubit quantum states and arbitrary local projective measurements. We then analyze in details the relation between the violation of the bilocality inequality and the CHSH inequality. Finally, we show how our method can be extended to the n -locality scenario consisting of n two-qubit quantum states distributed among $n+1$ nodes of a star-shaped network.

BackgroundViolence and other traumatic events, as well as psychiatric disorders are frequent in developing countries, but there are few population studies to show the actual impact of traumatic events in the psychiatric morbidity in low and middle-income countries (LMIC).AimsTo study the relationship between traumatic events and prevalence of mental disorders in São Paulo and Rio de Janeiro, Brazil.MethodsCross-sectional survey carried out in 2007-2008 with a probabilistic representative sample of 15- to 75-year-old residents in Sao Paulo and Rio de Janeiro, Brazil, using the Composite International Diagnostic Interview.ResultsThe sample comprised 3744 interviews. Nearly 90% of participants faced lifetime traumatic events. Lifetime prevalence of any disorders was 44% in Sao Paulo and 42.1% in Rio de Janeiro. One-year estimates were 32.5% and 31.2%. One-year prevalence of traumatic events was higher in Rio de Janeiro than Sao Paulo (35.1 vs. 21.7; pConclusionOur findings show that psychiatric disorders and traumatic events, especially violence, are extremely common in Sao Paulo and Rio de Janeiro, supporting the idea that neuropsychiatric disorders and external causes have become a major public health priority, as they are amongst the leading causes of burden of disease in low and middle-income countries. The comparison between the two cities regarding patterns of violence and psychiatric morbidity suggests that environmental factors may buffer the negative impacts of traumatic events. Identifying such factors might guide the implementation of interventions to improve mental health and quality of life in LMIC urban centers.

In high income, developed countries, health status tends to improve as income increases, but primarily through the 50(th)-66(th) percentile of income. It is unclear whether the same limitation holds in middle income countries, and for both general assessments of health and specific conditions.Data were obtained from Brazil, a middle income country. In-person interviews with a representative sample of community residents age ≥ 60 (N=6963), in the southern state of Rio Grande do Sul, obtained information on demographic characteristics including household income and number of persons supported, general health status (self-rated health, functional status), depression, and seven physician-diagnosed, self-reported health conditions. Analyses used household income (adjusted for number supported and economies of scale) together with higher order income terms, and controlled for demographics and comorbidities, to ascertain nonlinearity between income and general and specific health measures.In fully controlled analyses income was associated with general measures of health (linearly with self-rated health, nonlinearly with functional status). For specific health measures there was a consistent linear association with depression, pulmonary disorders, renal disorders, and sensory impairment. For musculoskeletal, cardiovascular (negative association), and gastrointestinal disorders this association no longer held when comorbidities were controlled. There was no association with diabetes.Contrary to findings in high income countries, the association of household-size-adjusted income with health was generally linear, sometimes negative, and sometimes absent when comorbidities were controlled.

OBJECTIVE: Estimate the prevalence of psychotropic drugs use in the city of Rio de Janeiro, Brazil, and establish its relationship with the presence of mental disorders. METHODS: A probabilistic sample of non-institutionalized individuals, from the general population of Rio de Janeiro (n = 1208;turn out:81%), 15 years or older, who were interviewed using the Composite International Diagnostic Interview 2.1 (depression, anxiety-phobia, OCD\PTSD, alcoholism sections), and asked about their psychotropic use during a 12 and one-month period before the interview. Data were collected between June/2007-February/2008.The prevalence was estimated with a confidence interval of 95%. The associations between psychotropics use and mental disorders were analyzed through a logistic regression model (Odds Ration - OR). RESULTS: The one-month prevalence of psychotropic drug use was 6.55%, 3.19% for men and 9.13% for women. Antidepressants were the most frequently used drug (2.78%), followed by anorectics (1.65%), tranquilizers (1.61%) and mood stabilizers (1.23%). General practitioners issued the highest number of prescriptions (46.3%), followed by psychiatrists (29.3%); 86.6% of the psychotropic drugs used were paid for by the patient himself. Individuals with increased likelihood of using psychotropic drugs were those that had received a psychiatric diagnosis during a one-month period before the study (OR:3.93), females (OR:1.82), separated/divorced (OR:2.23), of increased age (OR:1.03), with higher income (OR:2.96), and family history of mental disorder (OR:2.59); only 16% of the individuals with a current DSM IV diagnosis were using a psychotropic drug; 17% among individuals with a depression-related diagnosis and 8% with Phobic Anxiety Disorders-related diagnosis used psychotropics. CONCLUSION: Approximately 84% of individuals displaying some mental disorder did not use psychotropic drugs, which indicates an important gap between demand and access to treatment. A significant failure is evident in the health system for patients with mental disorders; this could be due to health workers' inability to recognize mental disorders among individuals.

Stromal elements within a tumor interact with cancer cells to create a microenvironment that supports tumor growth and survival. Adrenomedullin (ADM) is an autocrine/paracrine factor produced by both stromal cells and cancer cells to create such a microenvironment. During differentiation of macrophages, ADM is produced in response to pro-inflammatory stimuli and hypoxia. In this study we investigated the role of ADM as a growth factor for ovarian cancer cells and as a modulator of macrophages. We also analyzed ADM expression levels in a retrospective clinical study using nanofluidic technology and assessment of ADM at the gene level in 220 ovarian cancer patients. To study the effects of ADM, ovarian cancer cell lines A2780, OVCAR-3, and HEY and their drug-resistant counterparts were used for proliferation assays, while monocytes from healthy donors were differentiated in vitro. ADM was a weak growth factor, as revealed by proliferation assays and cell cycle analysis. After culturing cancer cells under stressing conditions, such as serum starvation and/or hypoxia, ADM was found to be a survival factor in HEY but not in other cell lines. In macrophages, ADM showed activity on proliferation/differentiation, primarily in type 2 macrophages (M2). Unexpectedly, the clinical study revealed that high expression of ADM was linked to positive outcome and to cancer with low Ca125. In conclusion, although in vitro ADM was a potential factor in biological aggressiveness, this possibility was not confirmed in patients. Therefore, use of an ADM antagonist would be inappropriate in managing ovarian cancer patients.

Cervical cancer is the third most common cancer in women worldwide. Persistent infection with high-risk HPV types, principally HPV16 and 18 is the main risk factor for the development of this malignancy. However, the onset of invasive tumor occurs many years after initial exposure in a minority of infected women. This suggests that other factors beyond viral infection are necessary for tumor establishment and progression. Tumor progression is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells themselves or tumor-associated fibroblasts or macrophages. Increased MMPs expression, including MMP-2, MMP-9 and MT1-MMP, has been observed during cervical carcinoma progression. These proteins have been associated with degradation of ECM components, tumor invasion, metastasis and recurrence. However, few studies have evaluated the interplay between HPV infection and the expression and activity of MMPs and their regulators in cervical cancer. We analyzed the effect of HPV16 oncoproteins on the expression and activity of MMP-2, MMP-9, MT1-MMP, and their inhibitors TIMP-2 and RECK in cultures of human keratinocytes. We observed that E7 expression is associated with increased pro-MMP-9 activity in the epithelial component of organotypic cultures, while E6 and E7 oncoproteins co-expression down-regulates RECK and TIMP-2 levels in organotypic and monolayers cultures. Finally, a study conducted in human cervical tissues showed a decrease in RECK expression levels in precancer and cancer lesions. Our results indicate that HPV oncoproteins promote MMPs/RECK-TIMP-2 imbalance which may be involved in HPV-associated lesions outcome.

Information on the prevalence and concomitants of arthritis in developing countries is sparse. It is unclear whether they are comparable to findings in developed countries. To ascertain the prevalence, demographic characteristics, and health-related concomitants of arthritis in older persons in the southern state of Rio Grande do Sul, Brazil, a middle income country.The state of Rio Grande do Sul, Brazil, was subdivided into nine regions. Stratified random sampling was used to identify 880 community residents age ≥60 years in each region. One region with suspect data was excluded. Of 7040 community residents contacted in eight regions, 6963 participated (1.1% refusal rate). In 1995, trained, monitored interviewers, using structured questionnaires, conducted in-home interviews gathering information on demographic characteristics (age, sex, race/ethnicity, education, income, living arrangements, employment status), health behaviors (physical activity, tobacco use, social activity), functional limitations, depression, and 15 self-reported health conditions, including arthritis. Data were analyzed using descriptive statistics and logistic regression.Arthritis, reported by 43% of the sample, was more prevalent in women, among the less educated, those with lower income, and higher age. Severity, but not prevalence, differed by race/ethnicity. Controlled analyses indicated significant association with female gender, lower education, and less social activity. Arthritis was associated with reduced odds of stroke, but increased odds of hypertension, varicosities, bronchitis, renal problems, headache, gastrointestinal disorders, and depression. Arthritis was not significantly associated with age or functional limitations, and associations did not differ by gender.The prevalence, demographic and health characteristics associated with self-reported arthritis in this southern state in Brazil are similar to findings elsewhere in Brazil, and in developed countries.