Trace elements concentrations (Zn, Cu, Pb, Cd, As and Hg) in the Mediterranean mussel (Mytilus galloprovincialis) and evaluation of mussel quality and possible human health risk from cultivated and wild sites of the southeastern Adriatic Sea, Montenegro

The Mediterranean mussel Mytilus galloprovincialis (L.) was collected from the fall 2005 to the winter 2009 from the six sites on the Montenegrin coastline. Two wild samples were collected from the open sea coastline, and two cultivated and two wild were from the Boka Kotorska Bay. The mussels soft tissue was analyzed for zinc, copper, lead, cadmium, arsenic and total mercury. Concentrations of these metals, in mg kg(-1) dry weight, ranged from 135-210 for Zn, 6.2-14.5 for Cu, 4.0-11.5 for Pb, 1.7-2.1 for Cd, 5.8-12.4 for As and 0.1-0.5 for Hg. The metals were found to be present in the samples at different levels, but not in concentrations higher than maximum residual levels prescribed by the European Union (EU) and US Food and Drug Administration (USFDA) regulations for seafood. This indicates that the consumption of wild or cultivated mussels from the studied area is safe in moderate quantities

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

The Impact of the COVID-19 pandemic on outdoor physical activities for people with disabilities, including the risks for psychophysical well-being

The restrictions and social distancing measures due to the COVID-19 pandemic have created many obstacles in the practice of outdoor physical activity (OPA) throughout the world, particularly for the most vulnerable people, such as those with disabilities. The aim of this study was to explore the impact of pandemic-related limitations on the OPA of an Italian cohort of people with disabilities practicing sports. A retrospective observational study was conducted using an online survey. The questionnaire was distributed to 121 disabled athletes who practiced different outdoor physical activities. A total of 96 completed the survey, which collected demographic data, information about daily outdoor physical activity and sports habits, and about physical and psychological health before and during the pandemic. The frequency of daily OPA per week, along with the hours of physical activity, significantly decreased during the pandemic compared to those of the year before (p &lt; 0.0001). A statistically significant deterioration was also found in the physical and mental well-being of disabled athletes during the pandemic (p &lt; 0.0001) when compared to those from the year before the advent of COVID-19. This research demonstrated the negative impact of COVID-19 restrictions on OPA levels and on the physical and mental well-being of athletes with disabilities. It also highlighted a new challenge regarding the sustainability and integration of the national health system, demonstrating the necessity of improving the consistent accessibility of people with disabilities to OPA, both under normal conditions and emergency situations, in order to guarantee their psychophysical well-being

Ectopic Wnt/Beta–Catenin Signaling Induces Neurogenesis in the Spinal Cord and Hindbrain Floor Plate

The most ventral structure of the developing neural tube, the floor plate (FP), differs in neurogenic capacity along the neuraxis. The FP is largely non-neurogenic at the hindbrain and spinal cord levels, but generates large numbers of dopamine (mDA) neurons at the midbrain levels. Wnt1, and other Wnts are expressed in the ventral midbrain, and Wnt/beta catenin signaling can at least in part account for the difference in neurogenic capacity of the FP between midbrain and hindbrain levels. To further develop the hypothesis that canonical Wnt signaling promotes mDA specification and FP neurogenesis, we have generated a model wherein beta–catenin is conditionally stabilized throughout the FP. Here, we unambiguously show by fate mapping FP cells in this mutant, that the hindbrain and spinal cord FP are rendered highly neurogenic, producing large numbers of neurons. We reveal that a neurogenic hindbrain FP results in the altered settling pattern of neighboring precerebellar neuronal clusters. Moreover, in this mutant, mDA progenitor markers are induced throughout the rostrocaudal axis of the hindbrain FP, although TH+ mDA neurons are produced only in the rostral aspect of rhombomere (r)1. This is, at least in part, due to depressed Lmx1b levels by Wnt/beta catenin signaling; indeed, when Lmx1b levels are restored in this mutant, mDA are observed not only in rostral r1, but also at more caudal axial levels in the hindbrain, but not in the spinal cord. Taken together, these data elucidate both patterning and neurogenic functions of Wnt/beta catenin signaling in the FP, and thereby add to our understanding of the molecular logic of mDA specification and neurogenesis

Students' sense-making of personalised feedback based on learning analytics

Although technological advances have brought about new opportunities for scaling feedback to students, there remain challenges in how such feedback is presented and interpreted. There is a need to better understand how students make sense of such feedback to adapt self-regulated learning processes. This study examined students’ sense-making of learning analytics–based personalised feedback across four courses. Results from a combination of thematic analysis and epistemic network analysis show an association between student perceptions of their personalised feedback and how these map to subsequent self-described self-regulated learning processes. Most notably, the results indicate that personalised feedback, elaborated by personal messages from course instructors, helps students refine or strengthen important forethought processes of goal-setting, as well as to reduce procrastination. The results highlight the need for instructors to increase the dialogic element in personalised feedback in order to reduce defensive reactions from students who hold to their own learning strategies. This approach may prompt reflection on the suitability of students’ current learning strategies and achievement of associated learning goals.&#x0D; Implications for practice or policy:&#x0D; &#x0D; Personalised feedback based on learning analytics should be informed by an understanding of students’ self-regulated learning.&#x0D; Instructors implementing personalised feedback should align this closely with the course curriculum.&#x0D; Instructors implementing personalised feedback in their courses should consider the relational element of feedback by using a positive tone.&#x0D; Personalised feedback can be further enhanced by increasing the dialogic element and by including more information about learning strategies.&#x0D; </jats:p

Prediction of Post-Concussive Behavioral Changes in a Rodent Model Based on Head Rotational Acceleration Characteristics

Quantifying injury tolerance for concussion is complicated by variability in the type, severity, and time course of post-injury physiological and behavioral changes. The current study outlined acute and chronic changes in behavioral metrics following rotational acceleration-induced concussion in rats. The Medical College of Wisconsin (MCW) rotational injury model independently controlled magnitude and duration of the rotational acceleration pulse. Increasing rotational acceleration magnitude produced longer recovery times, which were used in this study and our prior work as an assessment of acute injury severity. However, longer duration rotational accelerations produced changes in emotionality as measured using the elevated plus maze. Cognitive deficits were for the most part not apparent in the Morris water maze assessment, possibly due to the lower severity of rotational acceleration pulses incorporated in this study. Changes in emotionality evolved between acute and chronic assessments, in some cases increasing in severity and in others reversing polarity. These findings highlight the complexity of quantifying injury tolerance for concussion and demonstrate a need to incorporate rotational acceleration magnitude and duration in proposed injury tolerance metrics. Rotational velocity on its own was not a strong predictor of the magnitude or type of acute behavioral changes following concussion, although its combination with rotational acceleration magnitude using multivariate analysis was the strongest predictor for acute recovery time and some chronic emotional-type behavioral changes

Determination of Microstructural Changes By Severely Plastically Deformed Copper-Aluminum Alloy: Optical Study

Our work deals with the problem of producing a complex metal-ceramic composite using the processes of internal oxidation (IO) and severe plastic deformation. For this purpose, Cu-Al alloy with 0.4wt.% of Al was used. IO of sample serves in the first step of the processing as a means for attaining a fine dispersion of nanosized oxide particles in the metal matrix. Production technology continues with repeated application of severe plastic deformation (SPD) of the resulting metal-matrix composite to produce the bulk nanoscaled structural material. SPD was carried out with equal channel angular pressing (ECAP), which allowed that the material could be subjected to an intense plastic strain through simple shear. Microstructural characteristics of one phase and multiphase material was studied on internally oxidized Cu with 0.4wt.% of Al sample composed of one phase copper-aluminum solid solution in the core and fine dispersed oxide particles in the same matrix in the mantle region. In this manner AFM, X-ray diffraction and Raman spectroscopy were used. Local structures in plastically deformed samples reflect presence of Cu, CuO, Cu2O, Cu4O3 or Al2O3 structural characteristics, depending on type of sample

Multiple Promoters and Alternative Splicing: Hoxa5 Transcriptional Complexity in the Mouse Embryo

The genomic organization of Hox clusters is fundamental for the precise spatio-temporal regulation and the function of each Hox gene, and hence for correct embryo patterning. Multiple overlapping transcriptional units exist at the Hoxa5 locus reflecting the complexity of Hox clustering: a major form of 1.8 kb corresponding to the two characterized exons of the gene and polyadenylated RNA species of 5.0, 9.5 and 11.0 kb. This transcriptional intricacy raises the question of the involvement of the larger transcripts in Hox function and regulation.We have undertaken the molecular characterization of the Hoxa5 larger transcripts. They initiate from two highly conserved distal promoters, one corresponding to the putative Hoxa6 promoter, and a second located nearby Hoxa7. Alternative splicing is also involved in the generation of the different transcripts. No functional polyadenylation sequence was found at the Hoxa6 locus and all larger transcripts use the polyadenylation site of the Hoxa5 gene. Some larger transcripts are potential Hoxa6/Hoxa5 bicistronic units. However, even though all transcripts could produce the genuine 270 a.a. HOXA5 protein, only the 1.8 kb form is translated into the protein, indicative of its essential role in Hoxa5 gene function. The Hoxa6 mutation disrupts the larger transcripts without major phenotypic impact on axial specification in their expression domain. However, Hoxa5-like skeletal anomalies are observed in Hoxa6 mutants and these defects can be explained by the loss of expression of the 1.8 kb transcript. Our data raise the possibility that the larger transcripts may be involved in Hoxa5 gene regulation.Our observation that the Hoxa5 larger transcripts possess a developmentally-regulated expression combined to the increasing sum of data on the role of long noncoding RNAs in transcriptional regulation suggest that the Hoxa5 larger transcripts may participate in the control of Hox gene expression