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Abstract Global warming and the introduction of non-native fish represent major threats to freshwater biodiversity worldwide, but their effects have usually been investigated separately. Since most fish are ectotherms, their metabolism and feeding behaviour are highly influenced by temperature. Increasing water temperatures may thus exacerbate the impact of non-native fish, particularly those adapted to warmer conditions, on prey populations. Increasing temperature can also result in divergences between the impacts of females and males, especially in sexually dimorphic species. The globally invasive tropical guppy Poecilia reticulata Peters, a popular aquarium fish also used for control of mosquito-borne diseases and as a model species in ecological and evolutionary studies, exhibits strong sexual dimorphism and larvivory. This laboratory study examined prey consumption and prey size selection by guppies fed with chironomid larvae under varying temperature conditions. The effect of sex, pregnancy and prey body size on the guppy’s predatory response was also assessed by comparing Functional Responses. The results highlighted four key points: (1) increased temperature led to increased prey consumption in both females and males by decreasing handling time; (2) prey consumption was disproportionately higher in females than males, regardless of temperature; (3) temperature influenced females’ prey size selection; and (4) pregnancy reduced prey handling time among females. These findings show that temperature and intraspecific differences influence the feeding response of invasive fish, and they should both be taken into account when investigating and predicting the ecological impact of invasive species on invaded food webs.

Abstract Soybean and maize are some of the main drivers of Brazilian agribusiness. However, biotic and abiotic factors are of great concern, causing huge grain yield and quality losses. Phosphorus (P) deficiency is important among the abiotic factors because most Brazilian soils have a highly P-fixing nature. Thus, large amounts of phosphate fertilizers are regularly applied to overcome the rapid precipitation of P. Searching for alternatives to improve the use of P by crops is essential to reduce the demand for P input. The use of multifunctional rhizobacteria can be considered one of these alternatives. In this sense, the objective of the present work was to select and validate bacterial strains with triple action (plant growth promoter, phosphate solubilizer, and biocontrol agent) in maize and soybean, aiming to develop a multifunctional microbial inoculant for Brazilian agriculture. Bacterial strains with high indole acetic acid (IAA) production, phosphate solubilization, and antifungal activity against soil pathogenic fungi (Rhizoctonia solani, Macrophomina phaseolina, and Fusarium solani) were selected from the maize rhizosphere. Then, they were evaluated as growth promoters in maize under greenhouse conditions. Based on this study, strain 03 (Ag75) was selected due to its high potential for increasing biomass (root and shoot) and shoot P content in maize. This strain was identified through genomic sequencing as Bacillus velezensis. In field experiments, the inoculation of this bacterium increased maize and soybean yields by 17.8 and 26.5%, respectively, compared to the control (25 kg P2O5). In addition, the inoculation results did not differ from the control with 84 kg P2O5, indicating that it is possible to reduce the application of phosphate in these crops. Thus, the Ag75 strain has great potential for developing a multifunctional microbial inoculant that combines the ability to solubilize phosphate, promote plant growth, and be a biocontrol agent for several phytopathogenic fungi.

Abstract Background Acute hepatic porphyria (AHP) is a family of four rare genetic diseases, each involving deficiency in a hepatic heme biosynthetic enzyme. Resultant overproduction of the neurotoxic intermediates δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) leads to disabling acute neurovisceral attacks and progressive neuropathy. We evaluated the AHP disease burden in patients aged ≥ 12 years in a post hoc analysis of the Phase 3, randomized, double-blind, placebo-controlled ENVISION trial of givosiran (NCT03338816), an RNA interference (RNAi) therapeutic that targets the enzyme ALAS1 to decrease ALA and PBG production. We analyzed baseline AHP severity via chronic symptoms between attacks, comorbidities, concomitant medications, hemin-associated complications, and quality of life (QOL) and evaluated givosiran (2.5 mg/kg monthly) in patients with and without prior hemin prophylaxis on number and severity of attacks and pain scores during and between attacks. Results Participants (placebo, n = 46; givosiran, n = 48) included patients with low and high annualized attack rates (AARs; range 0–46). At baseline, patients reported chronic symptoms (52%), including nausea, fatigue, and pain; comorbidities, including neuropathy (38%) and psychiatric disorders (47%); concomitant medications, including chronic opioids (29%); hemin-associated complications (eg, iron overload); and poor QOL (low SF-12 and EuroQol visual analog scale scores). A linear relationship between time since diagnosis and AAR with placebo suggested worsening of disease over time without effective treatment. Givosiran reduced the number and severity of attacks, days with worst pain scores above baseline, and opioid use versus placebo. Conclusions Patients with AHP, regardless of annualized attack rates, have considerable disease burden that may partly be alleviated with givosiran.

Abstract Background The ABCG2, SLC22A12, and ALPK1 genes have been strongly associated with dysfunction of urate metabolism in patients with gout, but it is unknown how these transporters are expressed in patients with acute or chronic gout. Our objectives were to: (a) analyze the gene expression of urate transporters and of inflammation genes in peripheral blood from gout patients and controls; (b) determine whether the metabolic profile of gout patients can influence the gene expression profile and the expression of urate transporters, ABCG2 and SLC22A12, and inflammation molecules, ALPK1 and IL-1β, in peripheral blood leukocytes from gout patients; (c) compare them with their metabolic profile and the gene expression of people without gout and without hyperuricemia. Methods A total of 36 chronic and acute patients and 52 controls were recruited, and ABCG2, SLC22A12, IL-1β, and ALPK1 gene expression was evaluated by quantitative real-time PCR. Correlations of gene expression with clinical and laboratory parameters of patients were also analyzed. Results IL-1β was significantly increased in peripheral blood mononuclear cells (PBMCs) of patients compared with their polymorphonuclear leukocytes white blood cells (PMNLs, p

Abstract Color vision tests use estimative of threshold color discrimination or number of correct responses to evaluate performance in chromatic discrimination tasks. Both approaches have advantages and disadvantages. In the present investigation, we compared the number of errors during color discrimination task in normal trichromats and participants with color vision deficiency (CVD) using pseudoisochromatic stimuli at fixed saturation levels. We recruited 28 normal trichromats and eight participants with CVD. Cambridge Color Test was used to categorize their color vision phenotype, and those with a phenotype suggestive of color vision deficiency had their L- and M-opsin genes genotyped. Pseudoisochromatic stimuli were shown with target chromaticity in 20 vectors radiating from the background chromaticity and saturation of 0.06, 0.04, 0.03, 0.02, 0.01, and 0.005 u’v' units. Each stimulus condition appeared in four trials. The number of errors for each stimulus condition was considered an indicator of the participant's performance. At high chromatic saturation, there were fewer errors from both phenotypes. The errors of the normal trichromats had no systematic variation for high saturated stimuli, but below 0.02 u’v' units, there was a discrete prevalence of tritan errors. For participants with CVD, the errors happened mainly in red-green chromatic vectors. A three-way ANOVA showed that all factors (color vision phenotype, stimulus saturation, and chromatic vector) had statistically significant effects on the number of errors and that stimulus saturation was the most important main effect. ROC analysis indicated that the performance of the fixed saturation levels to identify CVD was better between 0.02 and 0.06 u’v’ units reaching 100%, while saturation of 0.01 and 0.005 u’v’ units decreased the accuracy of the screening of the test. We concluded that the color discrimination task using high saturated stimuli separated normal trichromats and participants with red-green color vision deficiencies with high performance, which can be considered a promising method for new color vision tests based in frequency of errors.

Abstract Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, $$\delta$$ δ -aminolaevulinic acid and porphyrins using a single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe, potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges, and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations.

Objetivo. Evaluar in silico y a nivel serológico el potencial antigénico del dominio extracelular recombinante de la proteína de ensamblaje de lipopolisacáridos - D (LptD) de Bartonella bacilliformis (dexr_LptD). Materiales y métodos. Mediante el análisis in silico se realizó la selección de una proteína de B. bacilliformis con potencial antigénico e inmunogénico. El gen de la proteína seleccionada se clonó en Escherichia coli TOP10 y se expresó en Escherichia coli BL21 (DE3) pLysS. La proteína recombinante fue expresada usando isopropil-β-D-1-tiogalactopiranósido (IPTG) y se optimizaron las condiciones de inducción. Por último, se purificó con resina Ni-IDA (His60 Ni Superflow) y se realizó un ensayo de Western Blot. Resultados: In silico, la proteína seleccionada fue LptD por estar localizada en la membrana externa y ser antigénica e inmunogénica. Las condiciones optimizadas para la inducción del dexr_LptD fueron 0,5 mM IPTG, 16 h, medio TB (Terrific Broth), etanol al 3% (v/v), 28 ºC, OD600: 1-1,5 y 200 r.p.m. La purificación se realizó en condiciones denaturantes a pequeña escala y se obtuvo 2,6 μg/mL de dexr_LptD parcialmente purificada. El ensayo de Western Blot mostró una reacción positiva entre los sueros provenientes de pacientes con la enfermedad de Carrión y dexr_LptD, ello evidencia la antigenicidad del dexr_LptD. Conclusiones. El dexr_LptD muestra antigenicidad in silico y a nivel serológico, estos resultados son base para posteriores estudios sobre candidatos vacunales contra la enfermedad de Carrión.

Esta revisão integrativa teve como objetivo identificar, analisar e sintetizar as evidências científicas produzidas sobre os entraves ao exercício dos direitos reprodutivos por mulheres vivendo com HIV / AIDS no Brasil e no mundo. As bases de dados PUBMED, Embase, Lilacs e Web of Science foram pesquisadas para identificar estudos primários sobre o assunto. Após a busca, foram encontrados 238 artigos e a amostra final dos estudos incluídos foi composta por 15 artigos. Após análise crítica dos estudos selecionados, concluiu-se que o estigma relacionado ao HIV, o despreparo dos profissionais de saúde e a desigualdade de gênero são obstáculos para que as mulheres vivendo com HIV / AIDS possam exercer seus direitos reprodutivos. Como resultado, enfatiza-se menos acesso à informação sobre seus direitos e as escolhas que as mulheres fazem em relação à sua sexualidade.

Background: High anthropometric indexes before sleeve gastrectomy (SG) are associated with an increased risk of erosive esophagitis (EE) in bariatric surgery candidates. Reasons that explain how these indexes influence the development of esophageal pathology after surgery remains unclear. Objectives: To assess the association between the body mass index (BMI), waist circumference (WC), and body fat percentage (BFP) with the development of EE in adults with obesity three months after SG. Setting: Clínica Avendaño, Lima, Peru. Methods: Retrospective cohort using a database including adults with obesity who underwent SG during 2017-2020. All the patients included had an endoscopy before and after the surgery. Sociodemographic, clinical and laboratory characteristics were compared according to BMI, WC and BFP, as well as by the development of de novo esophagitis. The association was evaluated by crude and adjusted generalized linear models with the log-Poisson family. Results: From a total of 106 patients, 23 (21.7%) developed EE. We did not find significant differences in sociodemographic, clinical and laboratory characteristics between patients with de novo EE compared to those who did not develop EE. After adjustment, BMI (aRR = 0.59, 95% CI = 0.18-1.40), BFP (aRR = 0.41, 95% CI = 0.15-1.19) and WC (aRR = 0.91, 95% CI = 0.69-1.16) were not associated with the development of EE three months post SG. Conclusions: We found no association between preoperative anthropometric indexes and the development of de novo EE; therefore, morbid obesity should not be a criterion to exclude the patients to undergo SG as primary surgery because of the risk of developing EE.

Cisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we used C. elegans to explore cisplatin effects on mitochondrial functions and investigate cisplatin-induced neurotoxicity through a high-resolution system for evaluating locomotion. First, we report that a high-glucose diet sensitizes C. elegans to cisplatin at the physiological level and that mitochondrial CED-13 protects the cell from cisplatin-induced oxidative stress. Additionally, by assessing mitochondrial function with a Seahorse XFe96 Analyzer, we observed a detrimental effect of cisplatin and glucose on mitochondrial respiration. Second, because catechol-O-methyltransferases (involved in dopamine degradation) are upregulated upon cisplatin exposure, we studied the protective role of dopamine against cisplatin-induced neurotoxicity. Using a Tierpsy Tracker system for measuring neurotoxicity, we showed that abnormal displacements and body postures in cat-2 mutants, which have dopamine synthesis disrupted, can be rescued by adding dopamine. Then, we demonstrated that dopamine treatment protects against the dose-dependent neurotoxicity caused by cisplatin.

Introduction Non-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet.Methods and analysis The Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects’ subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers.Ethics and dissemination The protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation.Trial registration number 2020-000130-18; NCT04798755.

Introducción: En la cirugía de carótida, el conocimiento anatómico resulta fundamental para disminuir el tiempo quirúrgico y las complicaciones. El objetivo del presente trabajo es estudiar la disposición de la vena facial respecto a la bifurcación carotídea y sus características anatómicas. Materiales y Métodos: 20 hemicuellos de cadáveres adultos fijados en solución de formaldehído. Se registró: longitud del “eje carotideo” (distancia en cm siguiendo el eje longitudinal de la carótida común e interna desde la clavícula hasta el borde superior del vientre posterior del digástrico) (L1); distancia de la bifurcación carotídea en el eje carotídeo (L2); distancia de la vena facial en el eje carotídeo (L3); distancia de la vena facial a la bifurcación carotídea (L4); cantidad de afluentes que recibía la vena facial y sitio de desembocadura. Resultados: L1 promedio 14 cm (rango 9.6-15); L2 promedio 10.1 cm (rango 7.5-12.5); L3 promedio 8.6 cm (rango 5-12.6). L4 promedio 1.3 cm (0.2-3.1). Discusión: en la mayoría de casos estudiados la vena facial se encontró por debajo a la bifurcación carotidea, no obstante, la distancia entre ambos fue en promedio 1,3cm, por lo cual podemos afirmar que se encuentran en proximidad la una con la otra. Conclusión: la proximidad entre la vena facial y la bifurcación carotídea encontrada en el presente estudio permite concluir que la vena facial es potencialmente útil como reparo anatómico para localizar la bifurcación carotidea en cirugía de carótida. Así también por su proximidad, la vena facial puede verse lesionada y dar así a complicaciones durante dicho procedimiento.

Abstract Background Medical faculties are currently embracing a modernistic approach to anatomical education that integrates diagnostic imaging largely through post-mortem computed tomography scanning of body donors. Post-mortem imaging, however, poses a multitude of challenges. The purpose of this study was to assess the implementation of pre-mortem donor-specific diagnostic imaging on student learning and dissection experience in addition to understanding the potential impact on students’ preparation for clinical practice. Methods Students in a fourth-year medicine elective course were divided into groups; group 1 received pre-mortem donor-specific diagnostic imaging, while group 2 received pathology-specific diagnostic imaging, a collection of images relating to the type(s) of pathologies the donors exhibited, though not specific to the donors themselves. Both groups also received a donor-specific case vignette. A convergent, parallel mixed methods design was employed. This included integrating data from group responses to a study participant survey and students’ academic assessment scores analyzed quantitatively through statistical analyses with data from focus group sessions investigating the psychosocial aspects of the student dissection experience and perceptions of the imaging use in the course analyzed qualitatively. Results As compared to students receiving pathology-specific diagnostic imaging, the quantitative results demonstrated that students receiving pre-mortem donor-specific diagnostic imaging more positively supported the relevancy of diagnostic imaging to their understanding of anatomy, valued the integration for future practice, and suggested an earlier integration within their medical curriculum. Qualitatively, two main themes were observed: the influence of diagnostic imaging integration on dissection experience and on professional mindset. Although both student groups received imaging corresponding to their body donor, consideration towards the humanistic nature of the body donor as a patient with a history was limited to student feedback from the donor- specific diagnostic imaging group. Conclusion Overall the integration of pre-mortem donor-specific diagnostic imaging into anatomical dissection provided students with practical skill development, an enhanced dissection experience, and reinforced personal qualities critical for future practice.

IntroductionRoutine health information system (RHIS) has been repeatedly updated to provide quality information. However, its timeliness has rarely been tracked. This study investigated the reporting status and the timeliness of quarterly reports of the national RHIS in the Philippines, based on its 19 years-operation in Palawan.MethodsWe analyzed the timeliness of 94.7% (1568/1656) of the quarterly reports that we obtained the date of receipt submitted by 22 health centers in Palawan from 1996 to 2014. The RHIS update in 2008 increased the number of reporting items and extended the submission due date since 2009 while computerized 15 health centers since 2011. We performed Fisher's exact test to examine changing the proportion of timely reports and multiple comparisons with permutation tests for changing the mean of the quarterly median lead times, median delays and interquartile ranges (IQR), for four periods of different operational requirements in the RHIS.ResultsThe update increased the timely reports from 6.7% (70/1045) to 22.4% (117/523) (pConclusionsMore attention must be paid to controlling the timeliness of RHIS when we introduce new interventions and perform daily management. Extending the due date increased timely reports. However, introducing unfamiliar tasks increased delay and uncertainty in timeliness. In a low-resource setting, an effective intervention needs to consider modest operating procedure changes that extend the existing routines to which the staff in charge has already accustomed.

Obesity is associated with an increased incidence and aggressiveness of breast cancer and is estimated to increment the development of this tumor by 50 to 86%. These associations are driven, in part, by changes in the serum molecules. Epidemiological studies have reported that Metformin reduces the incidence of obesity-associated cancer, probably by regulating the metabolic state. In this study, we evaluated in a breast cancer in-vitro model the activation of the IR-β/Akt/p70S6K pathway by exposure to human sera with different metabolic and hormonal characteristics. Furthermore, we evaluated the effect of brief Metformin treatment on sera of obese postmenopausal women and its impact on Akt and NF-κB activation. We demonstrated that MCF-7 cells represent a robust cellular model to differentiate Akt pathway activation influenced by the stimulation with sera from obese women, resulting in increased cell viability rates compared to cells stimulated with sera from normal-weight women. In particular, stimulation with sera from postmenopausal obese women showed an increase in the phosphorylation of IR-β and Akt proteins. These effects were reversed after exposure of MCF-7 cells to sera from postmenopausal obese women with insulin resistance with Metformin treatment. Whereas sera from women without insulin resistance affected NF-κB regulation. We further demonstrated that sera from post-Metformin obese women induced an increase in p38 phosphorylation, independent of insulin resistance. Our results suggest a possible mechanism in which obesity-mediated serum molecules could enhance the development of luminal A-breast cancer by increasing Akt activation. Further, we provided evidence that the phenomenon was reversed by Metformin treatment in a subgroup of women.

Response activation and inhibition are functions fundamental to executive control that are disrupted in Parkinson disease (PD). We used magnetoencephalography to examine event related changes in oscillatory power amplitude, peak latency and frequency in cortical networks subserving these functions and identified abnormalities associated with PD. Participants (N = 18 PD, 18 control) performed a cue/target task that required initiation of an un-cued movement (activation) or inhibition of a cued movement. Reaction times were variable but similar across groups. Task related responses in gamma, alpha, and beta power were found across cortical networks including motor cortex, supplementary and pre- supplementary motor cortex, posterior parietal cortex, prefrontal cortex and anterior cingulate. PD-related changes in power and latency were noted most frequently in the beta band, however, abnormal power and delayed peak latency in the alpha band in the pre-supplementary motor area was suggestive of a compensatory mechanism. PD peak power was delayed in pre-supplementary motor area, motor cortex, and medial frontal gyrus only for activation, which is consistent with deficits in un-cued (as opposed to cued) movement initiation characteristic of PD.

BackgroundIn the last decades, several clinical scores have been developed and currently used to improve the diagnosis and risk management of patients with suspected acute appendicitis (AA). However, some of them exhibited different values of sensitivity and specificity. We conducted a systematic review and metanalysis of epidemiological studies, which compared RIPASA and Alvarado scores for the diagnosis of AA.MethodsThis systematic review was conducted using PubMed and Web of Science databases. Selected studies had to compare RIPASA and Alvarado scores on patients with suspected AA and reported diagnostic parameters. Summary estimates of sensitivity and specificity were calculated by the Hierarchical Summary Receiver Operating Curve (HSROC) using STATA 17 (STATA Corp, College Station, TX) and MetaDiSc (version 1.4) software.ResultsWe included a total of 33 articles, reporting data from 35 studies. For the Alvarado score, the Hierarchical Summary Receiver Operating Curve (HSROC) model produced a summary sensitivity of 0.72 (95%CI = 0.66-0.77), and a summary specificity of 0.77 (95%CI = 0.70-0.82). For the RIPASA score, the HSROC model produced a summary sensitivity of 0.95 (95%CI = 0.92-0.97), and a summary specificity of 0.71 (95%CI = 0.60-0.80).ConclusionRIPASA score has higher sensitivity, but low specificity compared to Alvarado score. Since these scoring systems showed different sensitivity and specificity parameters, it is still necessary to develop novel scores for the risk assessment of patients with suspected AA.

Objetivo: Verificar o conhecimento produzido pelos pesquisadores a respeito da saúde do idoso com Doença de Alzheimer (DA). Métodos: Revisão integrativa da literatura com levantamento bibliográfico realizado na Biblioteca Virtual em Saúde (BVS), MEDLINE e nos bancos de dados do Portal de Periódicos Capes. Resultados: Observou-se a incipiência de artigos científicos publicados sobre a Doença de Alzheimer com enfoque na saúde da pessoa idosa. Conclusão: Verificou-se a necessidade de pesquisas para investigar a saúde do idoso em face à doença de Alzheimer que possibilitem aporte teórico na elaboração de políticas públicas de saúde mais abrangentes para os cuidados aos idosos. Descritores: Envelhecimento, Doença de Alzheimer, Autonomia pessoal, Saúde do idoso.

Although virtually all gene networks are predicted to be controlled by miRNAs, the contribution of this important layer of gene regulation to tissue homeostasis in adult animals remains unclear. Gain and loss-of-function experiments have provided key insights into the specific function of individual miRNAs, but effective genetic tools to study the functional consequences of global inhibition of miRNA activity in vivo are lacking. Here we report the generation and characterization of a genetically engineered mouse strain in which miRNA-mediated gene repression can be reversibly inhibited without affecting miRNA biogenesis or abundance. We demonstrate the usefulness of this strategy by investigating the consequences of acute inhibition of miRNA function in adult animals. We find that different tissues and organs respond differently to global loss of miRNA function. While miRNA-mediated gene repression is essential for the homeostasis of the heart and the skeletal muscle, it is largely dispensable in the majority of other organs. Even in tissues where it is not required for homeostasis, such as the intestine and hematopoietic system, miRNA activity can become essential during regeneration following acute injury. These data support a model where many metazoan tissues primarily rely on miRNA function to respond to potentially pathogenic events.

Abstract Objectives Patients with end-stage heart failure (ESHF) treated with ventricular assist devices (VADs) tend to gain weight after implantation, which is associated with higher complication rates and is a contraindication for heart transplantation (HT). The objective was to analyze the outcomes of obese patients with ESHF and VADs who underwent laparoscopic sleeve gastrectomy (LSG) at Ochsner Medical Center in New Orleans, which is the only program performing VADs and HT in the State of Louisiana, and also one of the largest VAD centers in the USA. Data description This dataset contains detailed baseline, perioperative, and long-term data of patients with VADs undergoing LSG. These variables were collected retrospectively from electronic medical records. Patients who achieved ≥ 50% excess BMI loss, BMI ≤ 35 kg/m2, listing for HT, HT, or myocardial recovery were identified and the timing to each of these milestones was documented. These data can be used alone or in combination with other datasets to achieve a larger sample size with more power for further analysis of these variables, which include the most important, standard, and objective bariatric and ESHF outcomes of patients with VADs undergoing LSG. Elaboration of composite outcomes is feasible.

Abstract Objectives Patients with end-stage heart failure (ESHF) treated with ventricular assist devices (VADs) tend to gain weight, which may prevent them from receiving heart transplantation (HT) if their body mass index (BMI) reaches ≥ 35 kg/m2. The objective was to synthesize all cases available in the literature and describe the most important outcomes of bariatric surgery (BS) in VAD patients, including BMI trends, reaching a BMI

Objetivos. Diseñar y evaluar una proteína multiepítope como candidato a vacuna contra la enfermedad de Carrión. Materiales y métodos. Mediante herramientas bioinformáticas se seleccionó epítopes de proteínas de membrana externa y se diseñó una proteína multiepítope. El gen de la proteína multiepítope fue subclonado en el plásmido de expresión pET28b y transformado en E. coli BL21 pLys. La proteína multiepítope fue expresada usando isopropil-β-D-1-tiogalactopiranósido y purificada usando resina. Esta proteína purificada fue utilizada para inmunizar ratones BALB/c y se obtuvo anticuerpos policlonales. Se realizaron ensayos de invasión in vitro usando una cepa de Bartonella bacilliformis (B. bacilliformis) a eritrocitos humanos. Resultados. La proteína multiepítope M1 presenta epítopes conservados entre aislamientos de B. bacilliformis, no tóxicos, no homólogos a proteínas humanas y superficiales. Los ratones inmunizados presentaron niveles de anticuerpos IgG capaces de reducir in vitro la tasa de invasión de B. bacilliformis a eritrocitos humanos. Conclusiones. La proteína multiepítope M1 podría servir como candidato a vacuna contra la enfermedad de Carrión; sin embargo, se requiere de más estudios para caracterizar el uso de este antígeno como vacuna.

Background: Tumor necrosis factor-like weak inducer of apoptosis (Tnfsf12; TWEAK) and its receptor Fibroblast growth factor-inducible 14 (Tnfrsf12a; Fn14) participate in the inflammatory response associated with vascular remodeling. However, the functional effect of TWEAK on vascular smooth muscle cells (VSMCs) is not completely elucidated. Methods: Next generation sequencing-based methods were performed to identify genes and pathways regulated by TWEAK in VSMCs. Flow-citometry, wound-healing scratch experiments and transwell migration assays were used to analyze VSMCs proliferation and migration. Mouse wire injury model was done to evaluate the role of TWEAK/Fn14 during neointimal hyperplasia. Findings: TWEAK up-regulated 1611 and down-regulated 1091 genes in VSMCs. Using a gene-set enrichment method, we found a functional module involved in cell proliferation defined as the minimal network connecting top TWEAK up-regulated genes. In vitro experiments in wild-type or Tnfrsf12a deficient VSMCs demonstrated that TWEAK increased cell proliferation, VSMCs motility and migration. Mechanistically, TWEAK increased cyclins (cyclinD1), cyclin-dependent kinases (CDK4, CDK6) and decreased cyclin-dependent kinase inhibitors (p15lNK4B) mRNA and protein expression. Downregulation of p15INK4B induced by TWEAK was mediated by mitogen-activated protein kinase ERK and Akt activation.Tnfrsf12a or Tnfsf12 genetic depletion and pharmacological intervention with TWEAK blocking antibody reduced neointimal formation, decreasing cell proliferation, cyclin D1 and CDK4/6 expression, and increasing p15INK4B expression compared with wild type or IgG-treated mice in wire-injured femoral arteries. Finally, immunohistochemistry in human coronary arteries with stenosis or in-stent restenosis revealed high levels of Fn14, TWEAK and PCNA in VSMCs enriched areas of the neointima as compared with healthy coronary arteries. Interpretation: Our data define a major role of TWEAK/Fn14 in the control of VSMCs proliferation and migration during neointimal hyperplasia after wire injury in mice, and identify TWEAK/Fn14 as a potential target for treating in-stent restenosis. Fund: ISCiii-FEDER, CIBERCV and CIBERDEM. Keywords: Restenosis, Proliferation, Cyclins, TWEAK, Fn14

This study aimed to report the contribution of strategies for monitoring and effecting the flow of care to those who had been detained in a psychiatric hospital at the Center for Psychosocial Care. In the results, 496 outpatients from psychiatric hospitalization were contacted, of whom 95 were admitted to CAPS, 22 were re-admitted, 108 attended another point in the Health Network, 89 were hospitalized for problems related to the use and abuse of psychoactive substances, 19 refused to attend CAPS II, 93 phones were not answered, 70 others. It is concluded that the effectiveness of the flow for follow-up of egresses requires innovation with mental health management plans that include this theme, also collective constructions of instruments with indicators of follow-up in the information system and innovation in the elaboration of technological resources as a digital platform with real-time access by distinguished and involved service professionals.

Para pacientes que sufren artrosis avanzada o en algunos casos de fractura de cadera, la solución quirúrgica que se propone es la cirugía ortopédica mayor. Alguno de estos pacientes requerirá transfusión de sangre o hemocomponentes, o ambos, antes o después de la intervención. El abordaje de la anemia en el paciente quirúrgico puede hacerse de manera liberal, sujeto a la indicación de cada cirujano, o en el contexto de un protocolo restrictivo de reposición. Con este último el beneficio en el ahorro de recursos se acompaña además de un menor número de complicaciones relacionadas con la administración de sangre alogénica. El objetivo específico de nuestro trabajo fue comparar la estrategia liberal con la terapia restrictiva transfusional. Ingresaron en el estudio 498 pacientes; de estos, 261 (52,4%) en el año 2014 sometidos a terapia liberal y 237 (47,6%) en el año 2015 a quienes se aplicó el protocolo de terapia restrictiva transfusional. Se transfundieron menos individuos y se indicaron 55% menos volúmenes de sangre con la estrategia restrictiva. Se presentaron diez casos de reacción transfusional, todas de tipo febril, ocho en 2014 y dos en 2015. Con respecto a la evolución funcional no se comprobó diferencia entre ambos grupos. En nuestra experiencia y de acuerdo a la literatura consultada, la terapia restrictiva permite alcanzar iguales resultados funcionales, con menor riesgo para el paciente y ahorraría recursos al sistema.

Abstract Background Studies assessing volumetric sex differences have provided contradictory results. Total intracranial volume (TIV) is a major confounding factor when estimating local volumes of interest (VOIs). We investigated how the number, size, and direction of sex differences in gray matter volume (GMv) vary depending on how TIV variation is statistically handled. Methods Sex differences in the GMv of 116 VOIs were assessed in 356 participants (171 females) without correcting for TIV variation or after adjusting the data with 5 different methods (VBM8 non-linear-only modulation, proportions, power-corrected-proportions, covariation, and the residuals method). The outcomes obtained with these procedures were compared to each other and to those obtained in three criterial subsamples, one comparing female-male pairs matched on their TIV and two others comparing groups of either females or males with large/small TIVs. Linear regression was used to quantify TIV effects on raw GMv and the efficacy of each method in controlling for them. Results Males had larger raw GMv than females in all brain areas, but these differences were driven by direct TIV-VOIs relationships and more closely resembled the differences observed between individuals with large/small TIVs of sex-specific subsamples than the sex differences observed in the TIV-matched subsample. All TIV-adjustment methods reduced the number of sex differences but their results were very different. The VBM8- and the proportions-adjustment methods inverted TIV-VOIs relationships and resulted in larger adjusted volumes in females, promoting sex differences largely attributable to TIV variation and very distinct from those observed in the TIV-matched subsample. The other three methods provided results unrelated to TIV and very similar to those of the TIV-matched subsample. In these datasets, sex differences were bidirectional and achieved satisfactory replication rates in 19 VOIs, but they were “small” (d

RESUMO: Objetivo: identificar a partir da história de vida das gestantes/puérperas usuárias de crack, as necessidades prioritárias que poderiam ajudá-las a reconstruir um viver sem drogas. Metodologia: Trata-se de uma pesquisa qualitativa do tipo estudo de caso, com três participantes sendo uma gestante e duas puérperas usuárias de crack, cujos dados foram coletados através de entrevistas semiestruturadas, realizadas entre outubro e dezembro/2015. Resultados: Apontaram como prioritárias as necessidades de proteger o filho; necessidade de apoio familiar; necessidade de uma relação de confiança com profissionais; e a necessidade espiritual. Conclusão: Reconstruir um viver sem drogas é um empreendimento coletivo que envolve a família, não apenas como um recurso, mas, também, como objeto de cuidado; os profissionais que precisam rever seus próprios valores e preconceitos; e do poder público, pois a não adesão dessa clientela aos serviços de saúde é uma forma de negligência também com as próximas gerações.

Background: High-density lipoproteins (HDL) are a complex mixture of lipids and proteins with vasculoprotective properties. However, HDL components could suffer post-translational modifications (PTMs) under pathological conditions, leading to dysfunctional HDL. We studied whether HDL are modified in abdominal aortic aneurysm (AAA) and the effect on HDL functionality. Methods: HDL were isolated by ultracentrifugation from AAA tissue (HDL-T) and from plasma of healthy volunteers and then incubated with AAA tissue-conditioned medium (HDL-AAA CM). PTMs from these particles were characterized using Comet-PTM. The ability of HDL-AAA CM for promoting cholesterol efflux was determined ex vivo and in vivo by using J774A.1 [3H]cholesterol-labeled mouse macrophages and after injecting [3H]cholesterol-labeled mouse macrophages and HDL into the peritoneal cavity of wild-type C57BL/6 mice, respectively. Trp50 and Trp108 oxidized forms of APOA1 in HDL incubated with conditioned-medium of activated neutrophils and in plasma of AAA patients and controls were measured by targeted parallel reaction monitoring. Findings: Oxidation was the most prevalent PTM in apolipoproteins, particularly in APOA1. Trp50 and Trp108 in APOA1 were the residues most clearly affected by oxidation in HDL-T and in HDL-AAA CM, when compared to their controls. In addition, cholesterol efflux was decreased in macrophages incubated with HDL-AAA CM in vitro and a decreased macrophage-to-serum reverse cholesterol transport was also observed in mice injected with HDL-AAA CM. Finally, both oxidized Trp50 and Trp108 forms of APOA1 were increased in HDL incubated with conditioned-medium of activated neutrophils and in plasma of AAA patients in relation to controls. Interpretation: Oxidative modifications of HDL present in AAA tissue and plasma were closely associated with the loss of vasculoprotective properties of HDL in AAA. Fund: MINECO, ISCiii-FEDER, CIBERDEM, CIBERCV and LA CAIXA. Keywords: Abdominal aortic aneurysm, HDL, Oxidative stress, Proteomics, Cholesterol efflux, Biomarkers

Abstract Objective There are three major serologic markers for hepatitis B virus (HBV) infection: hepatitis B surface antigen (HBsAg); hepatitis B surface antibody (anti-HBs); and hepatitis B core antibody (anti-HBc). HBV screening programs, however, often test only HBsAg and anti-HBs, missing those individuals who have anti-HBc as the only detectable marker. Isolated anti-HBc can represent chronic infection in which HBsAg is not detectable by serology. We, therefore, investigated the prevalence of isolated anti-HBc in an ethnic community at moderate to high risk for HBV infection. Results Of 7157 Korean American adults in New Jersey, 2736 (38.2%) lacked anti-HBs, potentially susceptible to HBV. Of these 2736 subjects, 771 subjects had anti-HBc. The prevalence of isolated anti-HBc increased with age: 0.8% (age 21–30); 2.4% (age 31–40); 6.05% (age 41–50); 11.7% (age 51–60); 18.3% (age 61–70); and 24.5% (age 71–91). Similarly, the percentage of the individuals with isolated anti-HBc in anti-HBs lacking subjects showed a striking age dependence. We conclude that serologic HBV screening should include anti-HBc to accurately assess the prevalence of HBV exposure. Serologic screening with only HBsAg and anti-HBs may overestimate the prevalence of non-immune population. It can also underestimate the prevalence of HBV and increase the risk of HBV reactivation during immunosuppression.

Objetivo: Conhecer e analisar os aspectos que os estudos da literatura nacional e internacional revelam sobre o perfil da mortalidade materna. Metodologia: Revisão da literatura, a busca foi realizada em agosto de 2017, por meio da Biblioteca Virtual em Saúde, nas bases de dados da Literatura Latino-Americana e do Caribe em Ciências da Saúde, Medical Literature Analysis and Retrieval System Online e, Base de dados da Enfermagem, estabelecendo-se critérios de inclusão e exclusão, sendo selecionados nove estudos. Resultados: O perfil epidemiológico dos óbitos maternos é influenciado por fatores sociais, os quais refletem as desigualdades que assolam o mundo, a disparidade nas formas de acesso aos serviços de saúde, a educação e demais fatores que repercutem num grupo vulnerável para índices alarmantes. Conclusões: Os estudos refletem a necessidade de maiores esforços com engajamento da sociedade, órgãos públicos, profissionais de saúde, com vista a maior comprometimento e co-resposabilização na luta pela redução da mortalidade materna.

Bacillary angiomatosis is a rare infection caused by Bartonella henselae or Bartonella quintana, which usually affects patients with the human immunodeficiency virus (HIV) and causes cutaneous and extracutaneous lesions; it is usually benign, but potentially fatal due to systemic involvement. A 49-year-old male, HIV-positive patient was admitted for fever, weight loss, respiratory distress, lymphadenopathy, edema, and multiple widespread angiomatous papules, which began 2 months prior to admission. He had pancytopenia, hypoalbuminemia and hepatosplenomegaly. Skin biopsy showed a well-demarcated nodular lesion with an epidermal collaret that enclosed the dermis, and proliferation of capillaries with hyperplasia and hypertrophy of the endothelial cells. Bacilli were observed with Warthin-Starry stain. He was treated with cotrimoxazole, obtaining resolution of skin lesions and other systemic disorders; however, after stopping therapy, he was readmitted because of recurrence, then he died. This case shows a clinical-pathological correlation of bacillary angiomatosis, which was confirmed by Warthin-Starry stain. In addition, it was associated with systemic findings supported by the thera­peutic response to antibiotics, the recurrence of the disease and the exclusion of other differential diagnoses. Despite the reduction of opportunist infections, this unusual disease could be present in some patients and affect skin and other tissues, which increases the probability of death, so physicians should recognize it and start therapy appropriately.

Esta investigación tiene como objetivo verificar el comportamiento de determinadas funciones ejecutivas (FE) en padres cuyos hijos presentan TEA y comparar este funcionamiento neurocognitivo con padres cuyos hijos no presentan la condición. Este análisis se realizó por medio de un diseño de estudio no experimental, de tipo descriptivo correlacional.Del análisis de estos resultados, se desprenden una tendencia a la baja a nivel de las FE de Memoria de Trabajo y Flexibilidad Cognitiva en el grupo experimental, sin alcanzar niveles de significancia, mientras que se identificó una tendencia al alza en las FE de Velocidad de Procesamiento e Inhibición en el mismo grupo. Los puntajes más altos podrían explicarse por una mejora a nivel de estas funciones, secundario al entrenamiento que implica atender a los desafíos de la crianza de niños con TEA. No obstante, se requiere un mayor tamaño muestral para confirmar si hay particularidades significativas en el funcionamiento cognitivo de los padres de niños con TEA que confirmen la presencia de un fenotipo ampliado.

(1) Background: Over the last few years, there has been growing interest in the whole genome sequencing (WGS) of rapidly mutating pathogens, such as influenza viruses (IVs), which has led us to carry out in-depth studies on viral evolution in both research and diagnostic settings. We aimed at describing and determining the validity of a WGS protocol that can obtain the complete genome sequence of A(H3N2) IVs directly from clinical specimens. (2) Methods: RNA was extracted from 80 A(H3N2)-positive respiratory specimens. A one-step RT-PCR assay, based on the use of a single set of specific primers, was used to retro-transcribe and amplify the entire IV type A genome in a single reaction, thus avoiding additional enrichment approaches and host genome removal treatments. Purified DNA was quantified; genomic libraries were prepared and sequenced by using Illumina MiSeq platform. The obtained reads were evaluated for sequence quality and read-pair length. (3) Results: All of the study specimens were successfully amplified, and the purified DNA concentration proved to be suitable for NGS (at least 0.2 ng/µL). An acceptable coverage depth for all eight genes of influenza A(H3N2) virus was obtained for 90% (72/80) of the clinical samples with viral loads >105 genome copies/mL. The mean depth of sequencing ranged from 105 to 200 reads per position, with the majority of the mean depth values being above 103 reads per position. The total turnaround time per set of 20 samples was four working days, including sequence analysis. (4) Conclusions: This fast and reliable high-throughput sequencing protocol should be used for influenza surveillance and outbreak investigation.

Pancreatic adenosquamous carcinoma (PASC) is an aggressive cancer whose mutational origins are poorly understood. An early study reported high-frequency somatic mutations affecting UPF1, a nonsense-mediated mRNA decay (NMD) factor, in PASC, but subsequent studies did not observe these lesions. The corresponding controversy about whether UPF1 mutations are important contributors to PASC has been exacerbated by a paucity of functional studies. Here, we modeled two UPF1 mutations in human and mouse cells to find no significant effects on pancreatic cancer growth, acquisition of adenosquamous features, UPF1 splicing, UPF1 protein, or NMD efficiency. We subsequently discovered that 45% of UPF1 mutations reportedly present in PASCs are identical to standing genetic variants in the human population, suggesting that they may be non-pathogenic inherited variants rather than pathogenic mutations. Our data suggest that UPF1 is not a common functional driver of PASC and motivate further attempts to understand the genetic origins of these malignancies.

Introduction Stress fractures are injuries produced by the overuse of certain extremities, generating repetitive fatigue in the bone with insufficient rest periods and hormonal disorders, among others. High osteoclastic activity and lower activity of the osteoblasts at the cortical level occurs. Objective To determine the factors associated with a stress fracture in a single medical center of the Peruvian navy. Methods We conducted an observational, analytical case-control study. The dependent variable was stress fracture confirmed by magnetic resonance imaging of the patients; the independent variables were age, sex, calcemia, socioeconomic status, and time of daily physical activity. All data were extracted from the medical records. Crude and adjusted odds ratios were calculated with 95% confidence intervals. Results The sample was comprised of 238 patients (119 cases and 119 controls), of which 79.8% were male, and 20.2% were female; the average age was 20.25. In the bivariate analysis, stress fractures were associated with male sex (odds ratio 3.00; 95% confidence interval 1.51 to 5.95), hypocalcemia (2.83; 2.32 to 3.44), more than two hours of daily physical activity (24.7; 12.51 to 48.95) and socioeconomic level C (6.66; 2.82 to 15.74). Time dedicated to physical activity (adjusted odds ratio 44.46; 95% confidence interval 17.93 to 110.22) and socioeconomic level C (adjusted odds ratio 22.57; 95% confidence interval 7.03 to 72.74) were associated in the multivariate analysis. Conclusion We found that stress fractures were associated with physical activity time and a lower socioeconomic level. Further studies are needed to evaluate the relationship with other factors in the military population of Peru.

INTRODUÇÃO: A Rede CUF em 18 de março, disponibilizou o Hospital CUF Infante Santo (HCIS) como hospital de referência para os doentes com COVID-19 na área da grande Lisboa. O internamento do doente não crítico (IDNC) ficou a cargo de uma equipa médica dedicada (EMD) constituída por médicos do Cluster Tejo, sob coordenação da Medicina Interna. Este estudo reporta as principais características demográficas e clínicas da população internada no IDNC. MATERIAL E MÉTODOS: Estudo retrospetivo analisando os doentes admitidos entre 27 de março e 7 de maio de 2020, no IDNC. Os critérios para diagnóstico de COVID-19 basearam-se na confirmação laboratorial e/ou critérios de diagnóstico imagiológicos. Excluíram-se da análise os doentes inicialmente suspeitos, mas cujo diagnóstico final encontrado foi outro. Clinicamente, o doente não crítico foi definido como tendo um Modified Early Warning Score (MEWS) entre 0-2. Os dados foram coletados do processo clínico eletrónico e da base de dados criada para seguimento destes doentes. Apresentam-se as características demográficas, clínicas, exames complementares, terapêutica e resultados. RESULTADOS: Incluíram-se 44 doentes, média de idades 67 anos, 52,3% homens. Divididos em grupos de acordo com a apresentação, com pneumonia em 75%, os restantes com outra apresentação. Proveniência: domicílio 81,8%, residência sénior 11,4% e outro hospital 8%. Fatores de risco para doença mais grave foram: Idade > 65 anos, 56,8%, hipertensão arterial 59%, doença respiratória crónica 15,9%, obesidade 15,9%, neoplasia ativa 13,6%, diabetes 11,4%, cardiopatia isquémica 11,4%, insuficiência cardíaca 6,8%, imunossupressão 6,8%, com índice de comorbilidades de Charlson média de 3.6. Agravamento clínico significativo com necessidade de escalar cuidados em três doentes (6,8%), em dois (4,5%) com ventilação mecânica invasiva, adicionalmente registado um óbito (2,3%). Demora média de internamento 10 dias, três (6,8%) doentes foram transferidos para outro hospital e 40 (91%) tiveram alta. DISCUSSÃO: A casuística apresentada representa o primeiro grupo de doentes não críticos internados com COVID-19 na Rede CUF da Região de Lisboa. Houve evolução e mortalidade intra-hospitalar abaixo do expectável para as características desta população, nomeadamente perante a presença de fatores de risco para doença mais grave e elevado índice de comorbilidades. CONCLUSÃO: A interpretação dos resultados obtidos fica condicionada ao pequeno tamanho da amostra e às incertezas ainda existentes nesta nova doença.

Climate, which sets broad limits for migrating species, is considered a key filter to species migration between contrasting marine environments. The Southeast Mediterranean Sea (SEMS) is one of the regions where ocean temperatures are rising the fastest under recent climate change. Also, it is the most vulnerable marine region to species introductions. Here, we explore the factors which enabled the colonization of the endemic Red Sea octocoral Melithaea erythraea (Ehrenberg, 1834) along the SEMS coast, using sclerite oxygen and carbon stable isotope composition (δ18OSC and δ13CSC), morphology, and crystallography. The unique conditions presented by the SEMS include a greater temperature range (∼15 °C) and ultra-oligotrophy, and these are reflected by the lower δ13CSCvalues. This is indicative of a larger metabolic carbon intake during calcification, as well as an increase in crystal size, a decrease of octocoral wart density and thickness of the migrating octocoral sclerites compared to the Red Sea samples. This suggests increased stress conditions, affecting sclerite deposition of the SEMS migrating octocoral. The δ18Osc range of the migrating M. erythraea indicates a preference for warm water sclerite deposition, similar to the native depositional temperature range of 21–28 °C. These findings are associated with the observed increase of minimum temperatures in winter for this region, at a rate of 0.35 ± 0.27 °C decade−1 over the last 30 years, and thus the region is becoming more hospitable to the Indo-Pacific M. erythraea. This study shows a clear case study of “tropicalization” of the Mediterranean Sea due to recent warming.

Alpha-1 antitrypsin deficiency is an autosomal co-dominant inherited disorder that results in decreased circulating levels of alpha-1 antitrypsin (also known as alpha-1 proteinase inhibitor) and predisposes affected individuals to early onset lung and liver disease. There is currently no cure for alpha-1 antitrypsin deficiency. However, appropriate treatment and a high standard of clinical care can prevent patients from being seriously affected and having to undergo major medical interventions, such as organ transplantation. Beyond managing the symptoms associated with alpha-1 antitrypsin deficiency, alpha-1 proteinase inhibitor therapy is the only treatment for the condition’s underlying cause. Early diagnosis is important to ensure efficient therapeutic strategies and to minimize further deterioration of lung function. alpha-1 antitrypsin deficiency is under diagnosed globally, partly because the disease has no unique presenting symptoms. This document was prepared by a Portuguese multidisciplinary group and it aims to set out comprehensive principles of care for Alpha-1 antitrypsin deficiency. These include the importance of registries, the need for clinical research, the need for consistent recommendations (regarding diagnosis, treatment and monitoring), the role of reference centres, the requirement for sustained access to treatment, diagnostic and support services, and the role of patient organizations.

Extracorporeal shock waves (ESWTs) are “mechanical” waves, widely used in regenerative medicine, including soft tissue wound repair. Although already being used in the clinical practice, the mechanism of action underlying their biological activities is still not fully understood. In the present paper we tried to elucidate whether a proinflammatory effect may contribute to the regenerative potential of shock waves treatment. For this purpose, we exposed human foreskin fibroblasts (HFF1 cells) to an ESWT treatment (100 pulses using energy flux densities of 0.19 mJ/mm 2 at 3 Hz), followed by cell analyses after 5 min, up to 48 h. We then evaluated cell proliferation, reactive oxygen species generation, ATP release, and cytokine production. Cells cultured in the presence of lipopolysaccharide (LPS), to induce inflammation, were used as a positive control, indicating that LPS-mediated induction of a proinflammatory pattern in HFF1 increased their proliferation. Here, we provide evidence that ESWTs affected fibroblast proliferation through the overexpression of selected cytokines involved in the establishment of a proinflammatory program, superimposable to what was observed in LPS-treated cells. The possibility that inflammatory circuits can be modulated by ESWT mechanotransduction may disclose novel hypothesis on their biological underpinning and expand the fields of their biomedical application.

Objetivo: evaluar el efecto de los análogos de GnRH sobre la predicción de talla final adulta en niñas con pubertad precoz central de diagnóstico tardío. Materiales y métodos: estudio descriptivo, retrospectivo. Se incluyeron niñas atendidas entre 2012 y 2018 en la Unidad de Endocrinología Pediátrica del Hospital Cayetano Heredia con diagnóstico de pubertad precoz central idiopática de diagnóstico tardío. Se realizó evaluación antropométrica, evaluación de estadío Tanner y determinación de edad ósea con el método de Greulich y Pyle, estimando la predicción de talla final adulta mediante el método de Bayley Pinneau antes y después del tratamiento con análogos de GnRH. Se realizó t de student para comparar la predicción de talla antes y después del tratamiento. Se consideró significativo un p< 0,05. Resultados: se incluyeron 23 niñas con edad cronológica media de 8,4 ± 0,4 años y una edad ósea de 10,7 ± 0,8 años al ingreso. El 83,9% de las pacientes tuvieron exceso de peso y el 74,0% estadio Tanner 3 al diagnóstico. El tiempo promedio de tratamiento con análogos de GnRH fue de 20,5 ± 8,4 meses. El efecto del tratamiento calculado con la diferencia de predicción de talla final adulta menos predicción de talla inicial fue de 2,5 ± 4,1 cm (p

Background: Intestinal coeliac auto-antibodies are the marker of coeliac disease (CD). Since the determination of these antibodies is still not widely available, we used immunoassays to identify the most suitable technology for revealing intestinal auto-antibodies in the wide clinical spectrum of CD. Methods: Intestinal auto-antibodies have been prospectively investigated in CD suspected children using two immunoassays: intestinal-deposits of IgA anti-tissue transglutaminase antibodies (anti-tTG) and biopsy-culture IgA anti-endomysium (AEA). Intestinal IgM antibodies have been determined in IgA-deficient subjects. Findings: Two-hundred and twenty-one suspected CD patients were enrolled. Intestinal antibodies were tested positive for both assays in classical CD patients (n = 178) with villous atrophy and positive serum-CD antibodies, potential CD patients (n = 16) with normal intestinal mucosa and positive serum-CD antibodies, and pre-potential CD patients (n = 14) with normal intestinal mucosa and negative serum-CD antibodies. In 13/221 with normal intestinal mucosa, negative CD-serum antibodies and negative intestinal antibodies CD has been excluded. All classical, 14/16 potential and 11/14 pre-potential CD patients on gluten-free diet (GFD) improved their symptoms. In 9/11 pre-potential patients intestinal antibodies disappeared on GFD. Both assays were negative in 69/71 control subjects. The two assays showed high diagnostic sensitivity (100%) and specificity (99%). Interpretation: Intestinal CD-antibodies make prompt diagnosis in the wide clinical spectrum of CD reducing the delay in diagnosis and treatment, especially in pre-potential CD patients. The easy handling biopsy culture assay is an effective diagnostic tool which should be carried out by any gastroenterology unit to recognize all CD clinical manifestations. Funding: Interreg Central-Europe, IRCCS “Burlo Garofolo”. Keywords: Biopsy culture, Coeliac disease, Diagnosis, Gluten-free diet, Intestinal deposits

Background: Dysregulation of splicing variants (SVs) expression has recently emerged as a novel cancer hallmark. Although the generation of aberrant SVs (e.g. AR-v7/sst5TMD4/etc.) is associated to prostate-cancer (PCa) aggressiveness and/or castration-resistant PCa (CRPC) development, whether the molecular reason behind such phenomena might be linked to a dysregulation of the cellular machinery responsible for the splicing process [spliceosome-components (SCs) and splicing-factors (SFs)] has not been yet explored. Methods: Expression levels of 43 key SCs and SFs were measured in two cohorts of PCa-samples: 1) Clinically-localized formalin-fixed paraffin-embedded PCa-samples (n = 84), and 2) highly-aggressive freshly-obtained PCa-samples (n = 42). Findings: A profound dysregulation in the expression of multiple components of the splicing machinery (i.e. 7 SCs/19 SFs) were found in PCa compared to their non-tumor adjacent-regions. Notably, overexpression of SNRNP200, SRSF3 and SRRM1 (mRNA and/or protein) were associated with relevant clinical (e.g. Gleason score, T-Stage, metastasis, biochemical recurrence, etc.) and molecular (e.g. AR-v7 expression) parameters of aggressiveness in PCa-samples. Functional (cell-proliferation/migration) and mechanistic [gene-expression (qPCR) and protein-levels (western-blot)] assays were performed in normal prostate cells (PNT2) and PCa-cells (LNCaP/22Rv1/PC-3/DU145 cell-lines) in response to SNRNP200, SRSF3 and/or SRRM1 silencing (using specific siRNAs) revealed an overall decrease in proliferation/migration-rate in PCa-cells through the modulation of key oncogenic SVs expression levels (e.g. AR-v7/PKM2/XBP1s) and alteration of oncogenic signaling pathways (e.g. p-AKT/p-JNK). Interpretation: These results demonstrate that the spliceosome is drastically altered in PCa wherein SNRNP200, SRSF3 and SRRM1 could represent attractive novel diagnostic/prognostic and therapeutic targets for PCa and CRPC. Keywords: Prostate cancer, Splicing, Spliceosome, SNRNP200, SRSF3, SRRM1, Therapeutic target

Automated acoustic recognition of birds is considered an important technology in support of biodiversity monitoring and biodiversity conservation activities. These activities require processing large amounts of soundscape recordings. Typically, recordings are transformed to a number of acoustic features, and a machine learning method is used to build models and recognize the sound events of interest. The main problem is the scalability of data processing, either for developing models or for processing recordings made over long time periods. In those cases, the processing time and resources required might become prohibitive for the average user. To address this problem, we evaluated the applicability of three data reduction methods. These methods were applied to a series of acoustic feature vectors as an additional postprocessing step, which aims to reduce the computational demand during training. The experimental results obtained using Mel-frequency cepstral coefficients (MFCCs) and hidden Markov models (HMMs) support the finding that a reduction in training data by a factor of 10 does not significantly affect the recognition performance.

Background Worldwide population has been increasingly exposed to ultra-processed foods, which are associated with obesity. Adolescence is a transition period of life and WHO recommends the surveillance of risk factors to the adolescents’ health, such as diet, because experiences in this phase can result in health risks. Objective To assess the trends in food consumption of adolescents from Brazilian capitals according to sociodemographic variables, based on data from the National Survey of School Health (PeNSE). Methods Data from in 2009, 2012 and 2015 of a total of 173,310 9th graders enrolled in public and private schools in Brazilian capitals and in the Federal District were assessed. Food consumption was assessed from regular consumption (five or more times a week) of healthy eating markers (beans; vegetables; fruit) and unhealthy eating markers (sweets; soft drinks; fried salty snacks). For sociodemographic variables, we considered macro regions; age; race/ skin color; gender; school administrative status. We assessed these markers trends for the population and, additionally, the analyses were stratified by gender, race/ skin color, and school administrative status. Statistical significance of the temporal trends was assessed by linear regression model. Results Over six years, three types of change in Brazilian adolescents’ diet were observed: decreasing regular consumption of beans, sweets and soft drinks, increasing regular consumption of vegetables, and stable consumption of fruit and fried salty snacks. Conclusion Brazilian adolescents’ diet composition has changed in a short period, and therefore it is necessary to monitor it to propose actions aimed at this public.

Climate change is causing detrimental changes in living organisms, including pathogens. This review aimed to determine how climate change has impacted livestock system management, and consequently, what factors influenced the gastrointestinal nematodes epidemiology in small ruminants under tropical conditions. The latter is orientated to find out the possible solutions responding to climate change adverse effects. Climate factors that affect the patterns of transmission of gastrointestinal parasites of domesticated ruminants are reviewed. Climate change has modified the behavior of several animal species, including parasites. For this reason, new control methods are required for controlling parasitic infections in livestock animals. After a pertinent literature analysis, conclusions and perspectives of control are given.