Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Pyrene Exposure on Sheepshead Minnow (Cyprinodon variegatus) Reproduction

Polycyclic aromatic hydrocarbons are known to adversely affect survival, growth, and reproduction in many aquatic species. Adult female sheepshead minnow, Cyprinodon varietagus (SHM), were exposed to chronic, low levels of pyrene (12.5, 25, or 50 μg/L nominal concentrations) and the impact on reproductive ability and larval survival was assessed. Viable egg production was significantly reduced in a dose-dependent manner following a 28-d exposure of SHM to pyrene, confirming reproductive dysfunction. Gonadosomatic index (GSI) values were unchanged with pyrene exposure, but histological assessment of ovarian development showed significant differences in reproductive phases in SHM exposed to pyrene for 28 d, with a greater percentage of prespawning and nonspawning females observed in the two highest pyrene concentrations. The percentage of embryos successfully hatching varied significantly among treatments, with lowest hatch occurring at 25 μg/L, but survival of larval fish to 14 d was not significantly different. These results suggest that chronic maternal exposure to low concentrations of pyrene has the potential to affect population structures by altering reproductive development and output as well as embryo/larval survival rates.
Pramipexole in treatment-resistant depression: a 16-week naturalistic study.

OBJECTIVE To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression. METHODS The study sample consisted of in-patients with major depressive episode, according to the DSM-IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a > 50% reduction of the Montgomery-Asberg Depressive Rating Scale (MADRS) total score and a score of I or 2 on the Clinical Global Impression scale (CGI-1) at endpoint. Side-effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES). RESULTS Thirty-seven patients were enrolled. Of these. 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses. 19 completed the 16-week follow-up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 +/- 8.4 at baseline to 13.9 +/- 11.5 at endpoint (p < 0.001) and the CGI-S decreased from 4.6 +/- 0.8 at baseline to 2.8 +/- 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI-I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events. CONCLUSIONS These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.
Could stored blood transfusions (SBT) alter the mechanisms implied in wound healing, in burned patients?

UNLABELLED Several years ago, researchers reported several complications produced after blood transfusions such as transfusion reactions, the transmission of a variety of infectious agents, etc. Recently, many authors appreciate that the stored blood transfusions (SBT) create an important damage for patients' life, because of oxygen metabolism disturbances, induced earlier, after three repeated transfusions and maintained longtime after. Our study proposed to note the consequences of SBT on wound healing, in burned patients, who were submitted to skin grafting and remained in hospital for a long period. We tried estimate the pathophysiological mechanisms implied in microcirculation's failure, microvascular systemic deficiency and death. RESULTS Critically patients receiving SBT repeated frequently (six times/monthly for skin grafting) have an oscillatory outcomes depending by the reactivity of their biological terrain, as reflected by a several parameters we have measured. CONCLUSIONS SBT administered as a restrictive transfusions to the patients with hemoglobin values <8 g% and hematocrit <35% has good effects on wound healing evolution.
In vitro formation of oropharyngeal biofilms on silicone rubber treated with a palladium/tin salt mixture.

Adhesion of yeasts and bacteria to silicone rubber is one of the first steps in the biodeterioration of indwelling, silicone rubber voice prostheses. In this paper, silicone rubber, so-called "Groningen button," voice prostheses were treated with a colloidal palladium/tin solution to form a thin metal coat intended to discourage biofilm formation. First it was demonstrated that this treatment did not negatively affect the airflow resistance of the prostheses or induce any cytotoxicity. Subsequently, palladium/tin-treated voice prostheses were placed in a modified Robbins device together with untreated control prostheses to evaluate biofilm formation. Biofilms were formed by inoculating the device for 3 days with the total cultivable microflora obtained from an explanted, malfunctioning voice prosthesis supplemented with separately isolated yeasts (Candida albicans and Candida tropicalis). After 3 days the device was perfused three times daily with growth medium and phosphate-buffered saline. The device was allowed to drain between perfusions to better mimic the conditions in the oropharynx (moist but not always fully wetted). After 9 days the total number of bacterial and fungal colony-forming units on the prostheses were determined microbiologically, and scanning electron micrographs were taken of the valve sides. Biofilm formation was significantly less on the heavily treated palladium/tin prostheses than it was on the untreated prostheses although some ingrowing microcolonies also were observed on the treated prostheses. The spread of the biofilms was smaller on the treated prostheses than on the untreated ones.
Intrinsic functional connectivity variance and state‐specific under‐connectivity in autism

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with altered brain connectivity. Previous neuroimaging research demonstrates inconsistent results, particularly in studies of functional connectivity in ASD. Typically, these inconsistent findings are results of studies using static measures of resting‐state functional connectivity. Recent work has demonstrated that functional brain connections are dynamic, suggesting that static connectivity metrics fail to capture nuanced time‐varying properties of functional connections in the brain. Here we used a dynamic functional connectivity approach to examine the differences in the strength and variance of dynamic functional connections between individuals with ASD and healthy controls (HCs). The variance of dynamic functional connections was defined as the respective standard deviations of the dynamic functional connectivity strength across time. We utilized a large multicenter dataset of 507 male subjects (209 with ASD and 298 HC, from 6 to 36 years old) from the Autism Brain Imaging Data Exchange (ABIDE) to identify six distinct whole‐brain dynamic functional connectivity states. Analyses demonstrated greater variance of widespread long‐range dynamic functional connections in ASD (P < 0.05, NBS method) and weaker dynamic functional connections in ASD (P < 0.05, NBS method) within specific whole‐brain connectivity states. Hypervariant dynamic connections were also characterized by weaker connectivity strength in ASD compared with HC. Increased variance of dynamic functional connections was also related to ASD symptom severity (ADOS total score) (P < 0.05), and was most prominent in connections related to the medial superior frontal gyrus and temporal pole. These results demonstrate that greater intraindividual dynamic variance is a potential biomarker of ASD. Hum Brain Mapp 38:5740–5755, 2017. © 2017 Wiley Periodicals, Inc.
Intracellular presence of insulin and its phosphorylated receptor in non‐small cell lung cancer

Insulin has been known for a long time to influence the growth and differentiation of normal and transformed cells. In order to delineate the role of insulin specifically in non‐small cell lung cancer (NSCLC), we have now searched by immunohistochemistry (IHC) for the presence of insulin in NSCLC samples. Among the 112 samples we studied, 30 were found to contain insulin, which was detected in the form of intracytoplasmic granula. Moreover, its expression significantly correlated with (a) the morphological/histopathological subtype of NSCLC, being more frequent in adenocarcinomas; (b) the grade of tumor differentiation, displaying an increase in low‐grade carcinomas; (c) tumor size, occurring predominantly in smaller tumors; (d) the presence of phosphorylated, activated insulin receptor; (e) the median patient age, being present in relatively younger individuals. Furthermore and interestingly, surrounding atypical adenomatous hyperplastic areas and normal alveolar pneumocytes scored insulin‐positive in some of the insulin‐negative tumors. In addition, PCR exploration for insulin transcripts in some samples positive for immunoreactive insulin was negative, indicating a possibly exogenous origin for the intracellular insulin in our NSCLC cohort. Taken together, our data suggest that an intracellular insulin activity is important for the progression of low‐grade human lung adenocarcinomas. J. Cell. Physiol. 221: 766–770, 2009. © 2009 Wiley‐Liss, Inc.
Secondary prevention of acute kidney injury

Purpose of reviewSecondary prevention follows identification of acute kidney injury (AKI), in which functional outcome is incomplete. Secondary prevention requires biomarkers for early diagnosis and response to appropriate treatment, on-going injury and repair, and meaningful metrics to monitor outcome. This review summarizes recent research in these areas. Recent findingsProteomics and genetic studies have identified new risk factors and biomarkers of AKI. Biomarker performance studies reveal differences in prognostic performance according to population and AKI definition. The first early secondary prevention study utilizing a urinary biomarker of AKI as a triaging tool to randomize to treatment has been completed. Recent creatinine-kinetic modelling has highlighted issues with defining AKI which continue to make comparison of treatment outcomes difficult. Biomarkers to monitor repair are emerging. SummaryThe prognostic performance of novel biomarkers of AKI in a range of clinical settings is encouraging and critical to effective secondary prevention. Identification of cause and time-course of specific biomarkers are required before biomarker panels for secondary prevention are developed. Agreed standards around reporting of biomarker studies would facilitate comparisons between studies. Phase-specific biomarkers are required to triage to phase-specific treatment.
Prospective evaluation of a clinical decision guideline to diagnose spinal epidural abscess in patients who present to the emergency department with spine pain.

OBJECT A spinal epidural abscess (SEA) is rare but potentially devastating if not diagnosed early. Unfortunately, diagnostic delays and associated neurological deficits are common. The objectives of this analysis were to explore the use of a novel clinical decision guideline to screen patients who present to the emergency department (ED) with spine pain for SEA and to determine the diagnostic test characteristics of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in patients at risk for SEA. METHODS This was a prospective, cohort analysis comparing the incidence of diagnostic delays and presence of motor deficits at the time of diagnosis before and after implementation of a novel decision guideline using risk factor assessment followed by ESR and CRP testing prior to definitive imaging. A delay was defined as either multiple ED visits or admission to a nonsurgical service without a diagnosis of SEA. A 9-month substudy was performed in all patients who presented to the ED with spine pain so that the diagnostic test characteristics of the ESR and CRP level could be defined. RESULTS A total of 55 patients with an SEA in the 9-year control period and 31 patients with an SEA in the 5-year study period were identified. Diagnostic delays were observed in 46 (83.6%) of 55 patients before guideline implementation versus 3 (9.7%) of 31 after guideline implementation (p < 0.001). Motor deficits were present at the time of diagnosis in 45 (81.8%) of 55 patients before guideline implementation versus 6 (19.4%) of 31 after guideline implementation (p < 0.001). The sensitivity and specificity of ESR in patients with an SEA risk factor were 100% and 67%, respectively. The receiver operating characteristic curve analysis revealed better test characteristics for ESR (area under curve 0.96) than for CRP (area under curve 0.81). CONCLUSIONS A treatment guideline incorporating risk factor assessment followed by ESR and CRP testing was highly sensitive and moderately specific in identifying ED patients with SEA. A decrease in diagnostic delays and a lower incidence of motor deficits at the time of diagnosis was observed.
Reactive angioendotheliomatosis or intravascular histiocytosis? An immunohistochemical and ultrastructural study in two cases of intravascular histiocytic cell proliferation

Two elderly women with complex medical histories presented with erythematous patches, in one case involving the face and forearms, and in the other both elbows. Punch biopsies from both patients revealed intravascular proliferations of medium‐sized and large cells with luminal occlusion typical of angioendotheliomatosis. Immunostaining did not show either lymphocytic or endothelial cell antigens but was consistent with a histiocytic differentiation of the intravascular cells in both cases, and was further substantiated by ultrastructural examination in one case. One patient received a course of cyclophosphamide therapy over 15 days. Skin lesions faded but did not disappear. The patient died 10 months later from cardiac and renal failure, which was most probably unrelated to the skin lesions. In the other case, lesions diminished but did not entirely resolve with treatment with low doses of oral prednisone. Angioendotheliomatosis can be divided into a malignant variant, which is an angiotropic lymphoma mostly of B‐cell phenotype, and a benign, reactive variant, which is characterized by a proliferation of cells expressing endothelial cell markers. Only one case of angioendotheliomatosis with cells of histiocytic differentiation has been published previously under the name of intravascular histiocytosis. Our cases are very similar to the latter. The question arises as to whether intravascular histiocytic cell proliferation is a neoplastic proliferation of histiocytes or an early stage of classic reactive angioendotheliomatosis representing the residual cells associated with organization of microthrombi, which will be later followed by endothelial cell proliferation.
Dynamic distinctions in the Na+/Ca2+ exchanger adopting the inward- and outward-facing conformational states

Na+/Ca2+ exchanger (NCX) proteins operate through the alternating access mechanism, where the ion-binding pocket is exposed in succession either to the extracellular or the intracellular face of the membrane. The archaeal NCX_Mj (Methanococcus jannaschii NCX) system was used to resolve the backbone dynamics in the inward-facing (IF) and outward-facing (OF) states by analyzing purified preparations of apo- and ion-bound forms of NCX_Mj-WT and its mutant, NCX_Mj-5L6–8. First, the exposure of extracellular and cytosolic vestibules to the bulk phase was evaluated as the reactivity of single cysteine mutants to a fluorescent probe, verifying that NCX_Mj-WT and NCX_Mj-5L6–8 preferentially adopt the OF and IF states, respectively. Next, hydrogen-deuterium exchange–mass spectrometry (HDX-MS) was employed to analyze the backbone dynamics profiles in proteins, preferentially adopting the OF (WT) and IF (5L6–8) states either in the presence or absence of ions. Characteristic differences in the backbone dynamics were identified between apo NCX_Mj-WT and NCX_Mj-5L6–8, thereby underscoring specific conformational patterns owned by the OF and IF states. Saturating concentrations of Na+ or Ca2+ specifically modify HDX patterns, revealing that the ion-bound/occluded states are much more stable (rigid) in the OF than in the IF state. Conformational differences observed in the ion-occluded OF and IF states can account for diversifying the ion-release dynamics and apparent affinity (Km) at opposite sides of the membrane, where specific structure-dynamic elements can effectively match the rates of bidirectional ion movements at physiological ion concentrations.
Measuring In Vivo Free Radical Production by the Outer Retina.

PURPOSE Excessive and continuously produced free radicals in the outer retina are implicated in retinal aging and the pathogenesis of sight-threatening retinopathies, yet measuring outer retinal oxidative stress in vivo remains a challenge. Here, we test the hypothesis that continuously produced paramagnetic free radicals from the outer retina can be measured in vivo using high-resolution (22-μm axial resolution) 1/T1magnetic resonance imaging (MRI) without and with a confirmatory quench (quench-assisted MRI). METHODS Low-dose sodium iodate-treated and diabetic C57Bl6/J mice (and their controls), and rod-dominated (129S6) or cone-only R91W;Nrl-/- mice were studied. In dark-adapted groups, 1/T1 was mapped transretinally in vivo without or with (1) the antioxidant combination of methylene blue (MB) and α-lipoic acid (LPA), or (2) light exposure; in subgroups, retinal superoxide production was measured ex vivo (lucigenin). RESULTS In the sodium iodate model, retinal superoxide production and outer retina-specific 1/T1 values were both significantly greater than normal and corrected to baseline with MB+LPA therapy. Nondiabetic mice at two ages and 1.2-month diabetic mice (before the appearance of oxidative stress) had similar transretinal 1/T1 profiles. By 2.3 months of diabetes, only outer retinal 1/T1 values were significantly greater than normal and were corrected to baseline with MB+LPA therapy. In mice with healthy photoreceptors, a light quench caused 1/T1 of rods, but not cones, to significantly decrease from their values in the dark. CONCLUSIONS Quench-assisted MRI is a feasible method for noninvasively measuring normal and pathologic production of free radicals in photoreceptors/RPE in vivo.
Neutropenia during HIV Infection: Adverse Consequences and Remedies

Neutropenia frequently occurs in patients with Human immunodeficiency virus (HIV) infection. Causes for neutropenia during HIV infection are multifactoral, including the viral toxicity to hematopoietic tissue, the use of myelotoxic agents for treatment, complication with secondary infections and malignancies, as well as the patient's association with confounding factors which impair myelopoiesis. An increased prevalence and severity of neutropenia is commonly seen in advanced stages of HIV disease. Decline of neutrophil phagocytic defense in combination with the failure of adaptive immunity renders the host highly susceptible to developing fatal secondary infections. Neutropenia and myelosuppression also restrict the use of many antimicrobial agents for treatment of infections caused by HIV and opportunistic pathogens. In recent years, HIV infection has increasingly become a chronic disease because of progress in antiretroviral therapy (ART). Prevention and treatment of severe neutropenia becomes critical for improving the survival of HIV-infected patients.
Small-Subunit rRNA Genotyping of Rhizobia Nodulating Australian Acacia spp

ABSTRACT The structure of rhizobial communities nodulatingAcacia in southeastern Australia from south Queensland to Tasmania was investigated by a molecular approach. A total of 118 isolates from nodule samples from 13 different Acaciaspecies collected at 44 sites were characterized by small-subunit (SSU) ribosomal DNA (rDNA) PCR-restriction fragment length polymorphism analysis. Nine rhizobial genomospecies were identified, and these taxa corresponded to previously described genomospecies (B. Lafay and J. J. Burdon, Appl. Environ. Microbiol. 64:3989–3997, 1998). Eight of these genomospecies belonged to the Bradyrhizobiumlineage and accounted for 96.6% of the isolates. The remaining genomospecies corresponded to Rhizobium tropici. For analysis of geographic patterns, results were grouped into five latitudinal regions regardless of host origin. In each region, as observed previously for rhizobial isolates taken from non-Acacia legumes (Lafay and Burdon, Appl. Environ. Microbiol. 64:3989–3997, 1998), rhizobial communities were dominated by one or two genomospecies, the identities of which varied from place to place. Despite this similarity in patterns, the most abundant genomospecies for Acacia isolates differed from the genomospecies found in the non-Acacia-derived rhizobial collection, suggesting that there is a difference in nodulation patterns of the Mimosoideae and the Papilionoideae. Only two genomospecies were both widespread and relatively abundant across the range of sites sampled. Genomospecies A was found in all regions except the most northern sites located in Queensland, whereas genomospecies B was not detected in Tasmania. This suggests that genomospecies A might be restricted to the more temperate regions of Australia, whereas in contrast, genomospecies B occurs in different climatic and edaphic conditions across the whole continent. The latter hypothesis is supported by the presence of genomospecies B in southwestern Australia, based on partial SSU rDNA sequence data (N. D. S. Marsudi, A. R. Glenn, and M. J. Dilworth, Soil Biol. Biochem. 31:1229–1238, 1998).
Vitamin K Status Among Children With Cystic Fibrosis and Its Relationship to Bone Mineral Density and Bone Turnover

Objective. The aim of this study was to assess vitamin K status in an unselected population of children with cystic fibrosis (CF) and to investigate any vitamin K effect on bone turnover and bone mineral status. Methods. Children ≥5 years of age who were attending the CF unit were invited to enter the study. Fasting blood samples were analyzed for levels of vitamin K1 and prothrombin produced in vitamin K absence; total, undercarboxylated, and carboxylated osteocalcin (OC); and bone-specific alkaline phosphatase and procollagen I carboxy-terminal propeptide (bone formation markers). Levels of N-telopeptide and free pyridinoline and deoxypyridinoline (bone breakdown products) were measured in urine samples. Bone mineral density and bone mineral content were measured at the lumbar spine and for the total body with a GE Lunar Prodigy densitometer. Statistical analyses were performed with Minitab version 9.1. Results. One hundred six children entered the study. Sixty-five of 93 children (70%) from whom blood samples were obtained showed suboptimal vitamin K status, on the basis of low serum vitamin K1 levels, increased prothrombin produced in vitamin K absence levels, or both abnormalities. Vitamin K1 levels showed a significant negative correlation with undercarboxylated OC levels but showed no significant correlation with any marker of bone turnover or measurement of bone mineral status. Undercarboxylated OC levels were correlated significantly with bone turnover markers, which themselves showed a significant negative correlation with measurements of bone mineral density and content. There were no significant correlations between carboxylated or undercarboxylated OC levels and bone density measurements. Conclusions. Vitamin K1 deficiency is common among children with CF, and routine supplements should be considered. Through its role in the carboxylation of OC, vitamin K deficiency may be associated with an uncoupling of the balance between bone resorption and bone formation. A cause-effect relationship between vitamin K deficiency and low bone mass has not been proved.