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Electroencephalographic signals are obtained by amplifying and recording the brain's spontaneous biological potential using electrodes positioned on the scalp. While proven to help find changes in brain activity with a high temporal resolution, such signals are contaminated by non-stationary and frequent artefacts. A plethora of noise reduction techniques have been developed, achieving remarkable performance. However, they often require multi-channel information and additional reference signals, are not fully automated, require human intervention and are mostly offline. With the popularity of Brain-Computer Interfaces and the application of Electroencephalography in daily activities and other ecological settings, there is an increasing need for robust, online, near real-time denoising techniques, without additional reference signals, that is fully automated and does not require human supervision nor multi-channel information. This research contributes to the body of knowledge by introducing onEEGwaveLAD, a novel, fully automated, ONline, EEG wavelet-based Learning Adaptive Denoiser pipeline for artefact identification and reduction. It is a specific framework that can be instantiated for various types of artefacts paving the path towards real-time denoising. As the first of its kind, it is described and instantiated for the particular problem of blink detection and reduction, and evaluated across a general and a specific analysis of the signal to noise ratio across 30 participants.

Individual movements of bats are triggered by their life requirements, limited by their recognition of the environment and risks of moving, and mediated by habitat selection. Mining adds fragmentation and heterogeneity to landscapes, with poorly understood consequences to the life activities of the bats. Cave dwelling bats spend most of their life cycles within caves, and as they constantly forage in external landscapes, their contribution in the input of organic matter to the caves is of paramount importance to the subterranean biodiversity. We investigated habitat selection by cave bats in a mosaic of Amazonian forests, iron-rich savannas and iron-caves, studying the movements of the aerial insect-catcher Furipterus horrens (Furipteridae) and of the foliage gleaning bat Lonchorhina aurita (Phyllostomidae), both cave-dependent in the area. We used radio telemetry to assess their use of habitats, under the prediction that these species prefer preserved habitats for their foraging bouts, avoiding human-modified habitats. We also anticipated larger areas and commuting distances for both species when foraging in disturbed landscapes. Thirty-one bats were monitored in conserved habitats, mining sites and pastures resulting in an average range of 415.1 ± 837.4 ha and average commuting distances of 2163 ± 2453 m (F. horrens) and 681.1 ± 1101 ha and 2781.5 ± 2333 m (L. aurita). Our results suggest that F. horrens are open space foragers, frequently recorded in cangas, and L. aurita are forest foragers that use all habitats proportionally to their availability in the landscape. We detected landscape-related effects mediated by seasonal variation in the maximum commuting distance performed by both species. These are the first radiotelemetry data available for F. horrens and L. aurita, delivering original baselines to understand their movement behaviors. This information sheds light into constraints related to the optimal and adjusted biological cycles of these two species and their range shifts under scenarios of disturbance and may subsidize programs for their conservation.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Faces are a primary means of conveying social information between humans. One important factor modulating the perception of human faces is emotional expression. Face inversion also affects perception, including judgments of emotional expression, possibly through the disruption of configural processing. One intriguing inversion effect is an illusion whereby faces appear to be physically smaller when upright than when inverted. This illusion appears to be highly selective for faces. In this study, we investigated whether the emotional expression of a face (neutral, happy, afraid, and angry) modulates the magnitude of this size illusion. Results showed that for all four expressions, there was a clear bias for inverted stimuli to be judged as larger than upright ones. This demonstrates that there is no influence of emotional expression on the size underestimation of upright faces, a surprising result given that recognition of different emotional expressions is known to be affected unevenly by inversion. Results are discussed considering recent neuroimaging research which used population receptive field (pRF) mapping to investigate the neural mechanisms underlying face perception features and which may provide an explanation for how an upright face appears smaller than an inverted one. Elucidation of this effect would lead to a greater understanding of how humans communicate.

ObjectiveTo analyze the perceptions of professionals, caregivers, children, and adolescents with disabilities regarding the implementation of the My Abilities First (MAF) tool in Specialized Child Rehabilitation Centers (CERs).MethodThis is a qualitative research based on Reflexive Thematic Analysis (RTA). The study involved twenty-seven intentionally selected individuals, comprising 12 physiotherapists, 4 occupational therapists, 11 caregivers, 9 children and 2 adolescents. Participants completed sociodemographic and clinical questionnaires and took part in semi-structured online interviews, focusing on two themes: Positive health approaches and the MAF tool. The study was approved by the local ethics committee (opinion 4.779.175).ResultsReflexive Thematic Analysis of the interviews resulted in two themes: (1) Perceptions regarding the MAF tool as an educational and contributory process to enhance the inclusion and participation of children and adolescents with disabilities, and (2) Barriers and facilitators for the implementation process of the MAF tool. The implementation of MAF was identified as a driving factor in promoting equity and increased participation of children and adolescents with disabilities in various settings, including health, education, and leisure. Interviewees highlighted the need to confront attitudinal, communication, and social barriers that may hinder the implementation of the tool.ConclusionThe implementation of the MAF tool was perceived as an innovation due to its focus on the abilities of individuals with disabilities. However, there is a need to restructure it to broaden its scope and access to different contexts in order to confront barriers and enhance the inclusion and participation of children and adolescents with disabilities.

Photobiomodulation is a safe option for controlling pain, edema, and trismus when applied postoperatively in third molar surgery. However, administration prior to surgery has been under-explored. This study aims to explore the effectiveness of pre-emptive photobiomodulation in reducing postoperative edema in impacted lower third molar extractions. Two groups of healthy individuals undergoing tooth extraction will be randomly assigned: Control group receiving pre-emptive corticosteroid and simulated photobiomodulation, and Photobiomodulation Group receiving intraoral low-intensity laser and extraoral LED cluster application. The primary outcome will be postoperative edema after 48 h. The secondary outcomes will be pain, trismus dysphagia, and analgesic intake (paracetamol). These outcomes will be assessed at baseline as well as two and seven days after surgery. Adverse effects will be recorded. Data will be presented as means ± SD and a p-value < 0.05 will be indicative of statistical significance.

Electroencephalographic signals are obtained by amplifying and recording the brain's spontaneous biological potential using electrodes positioned on the scalp. While proven to help find changes in brain activity with a high temporal resolution, such signals are contaminated by non-stationary and frequent artefacts. A plethora of noise reduction techniques have been developed, achieving remarkable performance. However, they often require multi-channel information and additional reference signals, are not fully automated, require human intervention and are mostly offline. With the popularity of Brain-Computer Interfaces and the application of Electroencephalography in daily activities and other ecological settings, there is an increasing need for robust, online, near real-time denoising techniques, without additional reference signals, that is fully automated and does not require human supervision nor multi-channel information. This research contributes to the body of knowledge by introducing onEEGwaveLAD, a novel, fully automated, ONline, EEG wavelet-based Learning Adaptive Denoiser pipeline for artefact identification and reduction. It is a specific framework that can be instantiated for various types of artefacts paving the path towards real-time denoising. As the first of its kind, it is described and instantiated for the particular problem of blink detection and reduction, and evaluated across a general and a specific analysis of the signal to noise ratio across 30 participants. [ABSTRACT FROM AUTHOR]

Individual movements of bats are triggered by their life requirements, limited by their recognition of the environment and risks of moving, and mediated by habitat selection. Mining adds fragmentation and heterogeneity to landscapes, with poorly understood consequences to the life activities of the bats. Cave dwelling bats spend most of their life cycles within caves, and as they constantly forage in external landscapes, their contribution in the input of organic matter to the caves is of paramount importance to the subterranean biodiversity. We investigated habitat selection by cave bats in a mosaic of Amazonian forests, iron-rich savannas and iron-caves, studying the movements of the aerial insect-catcher Furipterus horrens (Furipteridae) and of the foliage gleaning bat Lonchorhina aurita (Phyllostomidae), both cave-dependent in the area. We used radio telemetry to assess their use of habitats, under the prediction that these species prefer preserved habitats for their foraging bouts, avoiding human-modified habitats. We also anticipated larger areas and commuting distances for both species when foraging in disturbed landscapes. Thirty-one bats were monitored in conserved habitats, mining sites and pastures resulting in an average range of 415.1 ± 837.4 ha and average commuting distances of 2163 ± 2453 m (F. horrens) and 681.1 ± 1101 ha and 2781.5 ± 2333 m (L. aurita). Our results suggest that F. horrens are open space foragers, frequently recorded in cangas, and L. aurita are forest foragers that use all habitats proportionally to their availability in the landscape. We detected landscape-related effects mediated by seasonal variation in the maximum commuting distance performed by both species. These are the first radiotelemetry data available for F. horrens and L. aurita, delivering original baselines to understand their movement behaviors. This information sheds light into constraints related to the optimal and adjusted biological cycles of these two species and their range shifts under scenarios of disturbance and may subsidize programs for their conservation. [ABSTRACT FROM AUTHOR]

Management regimes of marine resources that rely on spatial boundaries might be poorly adapted to climate change shifts in species distributions. This is of specific concern for the management of fish stocks that cross management jurisdictions, known as shared stocks. Transitioning to dynamic rules in spatial management has been suggested as a solution for mismatches between species distributions and the spatial boundaries. However, in many cases spatial boundaries are not clearly drawn, hampering such transitions. Here, we use black sea bass (Centropristis striata), summer flounder (Paralichthys dentatus) and scup (Stenotomus chrysops) as case studies to explore different approaches to designing spatial regulatory units to facilitate the adaptation of fisheries management to shifting distributions of shared stocks. First, we determine the yearly distribution of each stock within the United States Exclusive Economic Zone from 1951 to 2019 during Fall and Spring sampling seasons. Second, we explore two approaches for drawing regulatory units based on state waters and historical landings. Finally, we estimate each state’s proportion of the stock’s distribution and compare historical and recent values. We show that the distribution of all three stocks has changed relative to the years used to determine the current quota allocation across states, with an overall gain for central-northern states at the expense of the southernmost states. In terms of the distribution of allocation, we find that, while seasonal differences exist, the biggest differences in the proportion of the stock spatial distribution attributed to each state come from the method for designing regulatory units. Here, we show that the method used to define allocation units can have meaningful impacts on resulting adaptive policy. As climate change-driven conflicts in fishing resource allocation are expected to increase and deepen around the world, we provide a replicable approach to make an informed and transparent choice to support data-driven decision-making.

Plasmodium falciparum is a parasite that causes asymptomatic or symptomatic malaria infections in humans depending on various factors. These infections are also a major cause of anemia in intertropical countries such as Gabon. Past studies have clearly demonstrated that inflammatory markers such as cytokines play a key role in the pathogenesis of malaria disease. However, the clinical manifestations of severe malaria vary according to the level of transmission and more information is needed to gain a better understanding of the factors involved. As such, the objective of this study was to investigate the circulating levels of nine cytokines in asymptomatic and symptomatic P. falciparum infections in Gabonese children and their roles in the pathogenesis of anemia. Blood samples were collected from 241 children aged 3 to 180 months in Lastourville, south-eastern Gabon. Diagnosis of P. falciparum infection was performed using Rapid Diagnosis Tests, microscopy and nested PCR. Levels in the plasma of the Th1 (IFN-γ, TNF-α, IL-6 and IL-12p70), Th17 (IL-17A and IL-22) and Th2 (IL-10, IL-4 and IL-13) cytokines were measured by ELISA. Data showed that IL-6, IFN-γ, IL-12p70, IL-10, and IL-13 levels were significantly higher in children with symptomatic P. falciparum infection compared to uninfected children. IL-10 levels were significantly higher in symptomatic children than in asymptomatic children, who had moderately increased levels compared to uninfected controls. Moreover, only IL-10 and IL-6 levels were significantly higher in children with severe malarial anemia compared to children with uncomplicated malaria who had significantly lower IL-10 levels than children with moderate malarial anemia. These data indicate that the progression of P. falciparum infection towards an advanced stage in children is accompanied by a significant increase in type Th1 and/or Th2 cytokines. These inflammatory mediators could serve as potential predictors of anemia for malaria patients.

Changes in the organization and structure of the fibronectin matrix are believed to contribute to dysregulated wound healing and subsequent tissue inflammation and tissue fibrosis. These changes include an increase in the EDA isoform of fibronectin as well as the mechanical unfolding of fibronectin type III domains. In previous studies using embryonic foreskin fibroblasts, we have shown that fibronectin’s EDA domain (FnEDA) and the partially unfolded first Type III domain (FnIII-1c) function as Damage Associated Molecular Pattern (DAMP) molecules to stimulate the induction of inflammatory cytokines by serving as agonists for Toll-Like Receptor-4 (TLR4). However, the role of signaling molecules downstream of TLR-4 such as TGF-β Activated Kinase 1 (TAK1) and Mitogen activated protein kinases (MAPK) in regulating the expression of fibronectin DAMP induced inflammatory genes in specific cell types is not known. In the current study, we evaluate the molecular steps regulating the fibronectin driven induction of inflammatory genes in three human fibroblast cell lines: embryonic foreskin, adult dermal, and adult kidney. The fibronectin derived DAMPs each induce the phosphorylation and activation of TAK1 which results in the activation of two downstream signaling arms, IKK/NF-κB and MAPK. Using the specific inhibitor 5Z-(7)-Oxozeanol as well as siRNA, we show TAK1 to be a crucial signaling mediator in the release of cytokines in response to fibronectin DAMPs in all three cell types. Finally, we show that FnEDA and FnIII-1c induce several pro-inflammatory cytokines whose expression is dependent on both TAK1 and JNK MAPK and highlight cell-type specific differences in the gene-expression profiles of the fibroblast cell-lines.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.MethodsRECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.DiscussionRECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.RegistrationNCT05172024.

The pursuit of a quantitative approach to functional analysis of stone tools is an ongoing endeavour for traceologists. Technological advancements in 3D imaging techniques, such as photogrammetry/3D scanners, CT scanning, 3D digital microscopy, confocal microscopy, AFM and FEG-SEM and micro-topographical scanning, have greatly facilitated the detailed capturing of the geometry and surface texture at multiple levels of observation, from the object-scale to the nano-scale. However, while such technological innovations have predominantly focused on flaked assemblages, ground stone tools have only recently begun to receive due attention, and a standardised protocol for their study is yet to be established. In order to comprehend the function(s) of these tools, analytical techniques that enable a 3D visualisation of the entire item and the wear affecting the used surfaces have proven to be of great support. To this end, an analytical procedure was developed and tested on slabs and pebbles in order to replicate the use-wear traces observed on Upper Palaeolithic tools. The purpose was to assemble a site-specific reference collection tailored on the artefacts from the cultural level III of the Brînzeni I cave in north-west Moldova. Experimental replicas were used to treat different plant organs during controlled sequential experiments. The present article reports on the analysis based on photogrammetric data acquired during two stages of replicative usage. We tested multiple acquisition setups and elaborations to assess the geometry modification and the surface depletion. By exploring various acquisition strategies, a critical evaluation of potential sources of bias in data collection and subsequent elaboration were performed, and the methodology was accordingly adjusted thereby enhancing the reliability and reproducibility of the results. This study highlights the importance of carefully considering the acquisition strategy in archaeological related research to ensure accurate analyses and to validate robust interpretation.

The pathophysiological changes that occur after traumatic brain injury (TBI) can lead to the development of post-traumatic epilepsy, a life-long complication of brain trauma. The etiology of post-traumatic epilepsy remains unknown, but TBI brains exhibit an abnormal excitatory / inhibitory balance. In this study, we examine how brain injury alters susceptibility to chemically-induced seizures in C57Bl/6J mice, and if pharmacological enhancement of glutamate transporters can reduce chronic post-traumatic seizures. We found that controlled cortical impact (CCI) mice display delayed susceptibility to pentylenetetrazol (PTZ)-induced seizures. While CCI mice have no change in seizure susceptibility at 7d post-injury (dpi), at 70dpi they have reduced latency to PTZ-induced seizure onset, higher seizure frequency and longer seizure duration. Quantification of glutamate transporter mRNA showed that levels of Scl1a2 and Scl1a3 mRNA were increased at 7dpi, but significantly decreased at 70dpi. To test if increased levels of glutamate transporters can ameliorate delayed-onset seizure susceptibility in TBI mice, we exposed a new cohort of mice to CCI and administered ceftriaxone (200mg/kg/day) for 14d from 55-70dpi. We found that ceftriaxone significantly increased Scl1a2 and Scl1a3 in CCI mouse brain at 70dpi, and prevented the susceptibility of CCI mice to PTZ-induced seizures. This study demonstrates cortical impact can induce a delayed-onset seizure phenotype in mice. Delayed (55dpi) ceftriaxone treatment enhances glutamate transporter mRNA in the CCI brain, and reduces PTZ-induced seizures in CCI mice.

BackgroundIn Nigeria, there have been reports of widespread multiple antimicrobial resistance (AMR) amongst Salmonella isolated from poultry. To mitigate the impact of mortality associated with Salmonella on their farms, farmers resort to the use of antimicrobials without sound diagnostic advice. We conducted this study to describe the AMR patterns, mechanisms and genetic similarities within some Salmonella serovars isolated from different layer farms.MethodWe determine the AMR profiles of two hundred Salmonella isolates, selected based on frequency, serovar, and geographical and sample type distribution. We also assessed the mechanisms of multi-drug resistance for specific genetic determinants by using PCR protocols and gene sequence analysis. Pulsed-field gel electrophoresis (PFGE) was conducted on seven selected serovars to determine their genetic relatedness.ResultsOf 200 isolates, 97 (48.5%) revealed various AMR profiles, with the multiple antibiotic resistance (MAR) index ranging from 0.07-0.5. Resistance to ciprofloxacin was common in all the multi-drug resistant isolates, while all the isolates were susceptible to cefotaxime, ceftazidime, and meropenem. Genotypic characterization showed the presence of resistance genes as well as mutations in the nucleotide genes with subsequent amino acid substitutions. Fifteen isolates (43%) of S. Kentucky were indistinguishable, but were isolated from four different states in Nigeria (Ogun, n = 9; Kaduna, n = 6; Plateau, n = 3, and: Bauchi, n = 2). PFGE revealed 40 pulsotype patterns (Kentucky, n = 12; Larochelle, n = 9; Virchow, n = 5; Saintpaul, n = 4; Poona, n = 3; Isangi, n = 2, and; Nigeria, n = 2).ConclusionThis study recorded strictly related but diversely distributed Salmonella serovars with high AMR rates in poultry. We recommend strict regulation on antimicrobial use and regular monitoring of AMR trends among bacteria isolated from animals and humans to inform public policy.

Background This study investigated the associations between socio-economic deprivation and tuberculosis (TB) treatment outcomes, alongside well-known TB risk factors. The effects of healthcare expenditures and their growth on trends in TB incidence from 2009 to 2013 were also assessed. Methods Secondary data analysis was performed on data obtained from various sources including governmental, non-governmental and research institutions. Indicators for TB treatment outcomes included TB death rate, TB rate among the household contacts of the Index TB cases, TB treatment failure, HIV associated TB death rate, TB defaulter rate, and new TB smear positive cases. Analysis of variance (ANOVA) and Turkey’s tests for post-hoc analysis were used to compare means of variables of interest considering a type I error rate of 0.05. Regression models and canonical discriminant analysis (CDA) were used to explore the associations between trends in TB incidence and independent TB predictors. During CDA, Fischer’s linear functions, Eigen values, and Mahalanobis distances were determined with values of Wilk’s Lambda closer to zero being the evidence for well discriminated patient groups. Data analysis was performed using SPSS® statistical software version 23.0 (Chicago, IL). Results In total, 62 400 records of TB notification were analyzed for the period 2009–2013. The average TB incidence rate over a 5-year period was 298 cases per 100,000 inhabitants per year. The incidence of TB was reduced by 79.70% at the end of the evaluation as compared to the baseline data in 2009. Multiple linear regression analysis showed that the Expenditure per patient day equivalent (PDE) and PHC expenditure per capita were significantly and independently associated with the decline of TB incidence (adjusted R2 = 60%; ρ = 0.002) following the equation: Y = (- 209× Expenditure per PDE) + (- 0.191 × PHC expenditure per capita). CDA showed that in the most socio-economically deprived communities (quintile 1), HIV associated TB death rates were significantly more likely to be higher as compared to the least socio-economically deprived group (quintile 5) [Eigen value (12.95), function coefficient (1.49) > (.77); Wilk’s Lambda = .019, p < .0001]. Conclusions Although TB control programs in OR Tambo district have averted thousands of TB incident cases, their effects on HIV associated TB deaths among the most deprived communities remain insignificant. There is an urgent need for strengthening integration of TB/HIV services in most deprived settings.

In the present study, we evaluate the effect of acute restraint stress (15 min) of male Wistar rats on social interaction measurements and c-Fos immunoreactivity (c-Fos-ir) expression, a marker of neuronal activity, in areas involved with the modulation of acute physical restraint in rats, i.e., the paraventricular nucleus of the hypothalamus (PVN), median raphe nucleus (MnR), medial prefrontal cortex (mPFC), cingulate prefrontal cortex (cPFC), nucleus accumbens (NaC), hippocampus (CA3), lateral septum (LS) and medial amygdala (MeA). We considered the hypothesis that restraint stress exposure could promote social withdrawal induced by the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, and increase c-Fos expression in these limbic forebrain areas investigated. In addition, we investigated whether pretreatment with the atypical antipsychotic clozapine (5 mg/kg; I.P.) could attenuate or block the effects of restraint on these responses. We found that restraint stress induced social withdrawal, and increased c-Fos-ir in these areas, demonstrating that a single 15 min session of physical restraint of rats effectively activated the HPA axis, representing an effective tool for the investigation of neuronal activity in brain regions sensitive to stress. Conversely, pretreatment with clozapine, prevented social withdrawal and reduced c-Fos expression. We suggest that treatment with clozapine exerted a preventive effect in the social interaction deficit, at least in part, by blocking the effect of restraint stress in brain regions that are known to regulate the HPA-axis, including the cerebral cortex, hippocampus, hypothalamus, septum and amygdala. Further experiments will be done to confirm this hypothesis.

Different levels of arterial occlusive disease (aortoiliac, femoropopliteal, multi-level disease) can produce claudication symptoms in different leg muscle groups (buttocks, thighs, calves) in patients with peripheral artery disease (PAD). We tested the hypothesis that different locations of occlusive disease uniquely affect the muscles of PAD legs and produce distinctive patterns in the way claudicating patients walk. Ninety-seven PAD patients and 35 healthy controls were recruited. PAD patients were categorized to aortoiliac, femoropopliteal and multi-level disease groups using computerized tomographic angiography. Subjects performed walking trials both pain-free and during claudication pain and joint kinematics, kinetics, and spatiotemporal parameters were calculated to evaluate the net contribution of the calf, thigh and buttock muscles. PAD patients with occlusive disease affecting different segments of the arterial tree (aortoiliac, femoropopliteal, multi-level disease) presented with symptoms affecting different muscle groups of the lower extremity (calves, thighs and buttocks alone or in combination). However, no significant biomechanical differences were found between PAD groups during the pain-free conditions with minimal differences between PAD groups in the claudicating state. All statistical differences in the pain-free condition occurred between healthy controls and one or more PAD groups. A discriminant analysis function was able to adequately predict if a subject was a control with over 70% accuracy, but the function was unable to differentiate between PAD groups. In-depth gait analyses of claudicating PAD patients indicate that different locations of arterial disease produce claudication symptoms that affect different muscle groups across the lower extremity but impact the function of the leg muscles in a diffuse manner generating similar walking impairments.

[This corrects the article DOI: 10.1371/journal.pone.0245767.].

Language production has often been described as impaired in psychiatric diseases such as in psychosis. Nevertheless, little is known about the characteristics of linguistic difficulties and their relation with other cognitive domains in patients with a first episode of psychosis (FEP), either affective or non-affective. To deepen our comprehension of linguistic profile in FEP, 133 patients with FEP (95 non-affective, FEP-NA; 38 affective, FEP-A) and 133 healthy controls (HC) were assessed with a narrative discourse task. Speech samples were systematically analyzed with a well-established multilevel procedure investigating both micro- (lexicon, morphology, syntax) and macro-linguistic (discourse coherence, pragmatics) levels of linguistic processing. Executive functioning and IQ were also evaluated. Both linguistic and neuropsychological measures were secondarily implemented with a machine learning approach in order to explore their predictive accuracy in classifying participants as FEP or HC. Compared to HC, FEP patients showed language production difficulty at both micro- and macro-linguistic levels. As for the former, FEP produced shorter and simpler sentences and fewer words per minute, along with a reduced number of lexical fillers, compared to HC. At the macro-linguistic level, FEP performance was impaired in local coherence, which was paired with a higher percentage of utterances with semantic errors. Linguistic measures were not correlated with any neuropsychological variables. No significant differences emerged between FEP-NA and FEP-A (p≥0.02, after Bonferroni correction). Machine learning analysis showed an accuracy of group prediction of 76.36% using language features only, with semantic variables being the most impactful. Such a percentage was enhanced when paired with clinical and neuropsychological variables. Results confirm the presence of language production deficits already at the first episode of the illness, being such impairment not related to other cognitive domains. The high accuracy obtained by the linguistic set of features in classifying groups support the use of machine learning methods in neuroscience investigations.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

International and regional policies aimed at managing ocean ecosystem health need quantitative and comprehensive indices to synthesize information from a variety of sources, consistently measure progress, and communicate with key constituencies and the public. Here we present the second annual global assessment of the Ocean Health Index, reporting current scores and annual changes since 2012, recalculated using updated methods and data based on the best available science, for 221 coastal countries and territories. The Index measures performance of ten societal goals for healthy oceans on a quantitative scale of increasing health from 0 to 100, and combines these scores into a single Index score, for each country and globally. The global Index score improved one point (from 67 to 68), while many country-level Index and goal scores had larger changes. Per-country Index scores ranged from 41-95 and, on average, improved by 0.06 points (range -8 to +12). Globally, average scores increased for individual goals by as much as 6.5 points (coastal economies) and decreased by as much as 1.2 points (natural products). Annual updates of the Index, even when not all input data have been updated, provide valuable information to scientists, policy makers, and resource managers because patterns and trends can emerge from the data that have been updated. Changes of even a few points indicate potential successes (when scores increase) that merit recognition, or concerns (when scores decrease) that may require mitigative action, with changes of more than 10-20 points representing large shifts that deserve greater attention. Goal scores showed remarkably little covariance across regions, indicating low redundancy in the Index, such that each goal delivers information about a different facet of ocean health. Together these scores provide a snapshot of global ocean health and suggest where countries have made progress and where a need for further improvement exists.

PurposeTo assess the efficacy of vitrectomy in degenerative and tractional lamellar macular holes (LMHs) by meta-analysis of published studies.MethodsPubMed, Medline and Embase databases were searched up to May 2020. Included cohorts were divided into three groups: degenerative LMH group, lamellar hole associated epiretinal proliferation (LHEP) group and tractional LMH group. LHEP is likely to be associated with degenerative LMHs, but less commonly could be associated with mixed LMHs. To reduce risk of possible misclassification bias, eyes with LHEP which could not have been precisely classified by the authors, were included into the LHEP group. The primary outcome was to investigate the visual change following primary vitrectomy in the degenerative LMH and LHEP group versus the tractional LMH group. A sensitivity analysis excluding the LHEP group was also performed on the primary outcome. Mean difference (MD) in best corrected visual acuity between baseline and post-treatment was calculated, along with 95% confidence interval (CI). Rate of incidence of post-operative full-thickness macular hole (FTMH) was assessed as secondary outcome.ResultsThirteen studies were included. Pooled analyses including all groups showed a significant visual improvement following vitrectomy (pre-post MD = -0.17;95%CI = -0.22,-0.12;pConclusionPrimary vitrectomy for LMH ensured a favorable visual outcome, with no difference in visual gain between degenerative and tractional LMHs. However, a higher incidence of post-operative FTMHs was found in eyes with the degenerative LMH subtype.

The current study aimed to verify whether or not passive static stretching affects balance control capacity. Thirty-eight participants (19 women and 19 men) underwent a passive static stretching session, involving the knee extensor/flexor and dorsi/plantarflexor muscles, and a control session (no stretching, CTRL). Before (PRE), immediately after (POST), after 15 (POST15) and 30 min (POST30) from stretching (or rest in CTRL), balance control was evaluated under static and dynamic conditions, with open/closed eyes, and with/without somatosensory perturbation (foam under the feet). During tests, centre of pressure (CoP) sway area and perimeter and antero-posterior and medio-lateral sway mean speed were computed. Surface electromyography root mean square (sEMG RMS) was calculated from the vastus lateralis, biceps femoris, gastrocnemius medialis, and tibialis anterior muscles during MVC and during the balance tests. Hip flexion/extension and dorsi/plantarflexion range of motion (ROM), maximum voluntary contraction (MVC) and sEMG RMS during MVC were measured at the same time points. After stretching, ROM increased (≈6.5%; P

BackgroundBipolar Transurethral Enucleation of the Prostate (B-TUEP) is recommended as a first-choice treatment for benign prostatic obstruction in prostates >80 ml. Differently, B-TUEP is only considered as an alternative option after TURP for smaller prostates (30-80 ml). The aim of our study is to assess the relation between prostate size and surgical outcomes after B-TUEP.MethodsWe performed a retrospective analysis of data collected from 172 patients submitted to B-TUEP. Patients were segregated according to tertiles of prostate volume (PV) (≤60 ml, 61-110 ml, >110 ml). For each group we evaluated enucleation efficacy (enucleated weight/enucleation time), complication rates, urinary and sexual function parameters. Functional and sexual parameters were compared between groups at baseline, 1 and 3 months follow up. Descriptive statistics and linear and logistic regression models tested the association between PV and postoperative complications/outcomes.ResultsOperative time and weight of enucleated adenomas increased along with prostate volumes (all p≤0.01). Enucleation efficacy was higher in men with PV >110 ml compared to other groups (p≤0.001). Length of hospital stay, catheterization time and rates of postoperative complications, such as transfusion and clot evacuation rates and bladder neck/urethral strictures, were comparable between groups. Urinary symptoms improved at 1-and 3-months in each group as compared to baseline evaluation (all pConclusionAccording to our findings, B-TUEP should be considered a "size independent procedure" as it can provide symptom relief in men with prostates of all sizes with the same efficacy and safety profile.

Advanced ovarian cancer is one of the most lethal gynecological tumor, mainly due to late diagnoses and acquired drug resistance. MicroRNAs (miRNAs) are small-non coding RNA acting as tumor suppressor/oncogenes differentially expressed in normal and epithelial ovarian cancer and has been recognized as a new class of tumor early detection biomarkers as they are released in blood fluids since tumor initiation process. Here, we evaluated by droplet digital PCR (ddPCR) circulating miRNAs in serum samples from healthy (N = 105) and untreated ovarian cancer patients (stages I to IV) (N = 72), grouped into a discovery/training and clinical validation set with the goal to identify the best classifier allowing the discrimination between earlier ovarian tumors from health controls women. The selection of 45 candidate miRNAs to be evaluated in the discovery set was based on miRNAs represented in ovarian cancer explorative commercial panels. We found six miRNAs showing increased levels in the blood of early or late-stage ovarian cancer groups compared to healthy controls. The serum levels of miR-320b and miR-141-3p were considered independent markers of malignancy in a multivariate logistic regression analysis. These markers were used to train diagnostic classifiers comprising miRNAs (miR-320b and miR-141-3p) and miRNAs combined with well-established ovarian cancer protein markers (miR-320b, miR-141-3p, CA-125 and HE4). The miRNA-based classifier was able to accurately discriminate early-stage ovarian cancer patients from health-controls in an independent sample set (Sensitivity = 80.0%, Specificity = 70.3%, AUC = 0.789). In addition, the integration of the serum proteins in the model markedly improved the performance (Sensitivity = 88.9%, Specificity = 100%, AUC = 1.000). A cross-study validation was carried out using four data series obtained from Gene Expression Omnibus (GEO), corroborating the performance of the miRNA-based classifier (AUCs ranging from 0.637 to 0.979). The clinical utility of the miRNA model should be validated in a prospective cohort in order to investigate their feasibility as an ovarian cancer early detection tool.

A growing number of studies suggest that the frequency of numeracy experiences that parents provide at home may relate to children's mathematical development. However, the relation between home numeracy practices and children's numerical skills is complex and might depend upon both the type and difficulty of activities, as well as the type of math skills. Studies have also argued that this relation may be driven by factors that are not systematically controlled for in the literature, including socio-economic status (SES), parental math skills and children's IQ. Finally, as most prior studies have focused on preschoolers, it remains unclear to what extent there remains a relation between the home numeracy environment and math skills when children are in elementary school. In the present study, we tested an extensive range of math skills in 66 8-year-olds, including non-symbolic quantity processing, symbolic number understanding, transcoding, counting, and mental arithmetic. We also asked parents to complete a questionnaire about their SES, academic expectations, academic attitudes, and the numeracy practices that they provide at home. Finally, we measured their arithmetic fluency as a proxy for parental math skills. Over and above differences in socio-economic status, parental arithmetic fluency, child's IQ, and time spent with the child, we found a positive relation between the frequency of formal numeracy practices that were at or above grade level and two separate measures of mental arithmetic. We further found that the frequency of these advanced formal numeracy practices was related to parents' academic expectations. Therefore, our study shows that home numeracy experiences predict arithmetic skills in elementary school children, but only when those activities are formal and sufficiently challenging for children.

Introduction and aimComorbidities and comedication are common in patients with hepatitis C, which could result in a risk of drug-drug interaction. The objective of this study was to evaluate the prevalence of comorbidities, comedication and drug-drug interactions involving direct-acting antivirals in this population.MethodsComorbidities and comedications were evaluated in a retrospective cohort of hepatitis C patients. Drug-drug interactions were estimated in real life and with simulated data on comedications following drug regimens: telaprevir; elbasvir/grazoprevir, ombitasvir/paritaprevir/r/ritonavir (2D regimen), and sofosbuvir/simeprevir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir; 2D/dasabuvir (3D regimen); glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir. The interactions were evaluated according to the University of Liverpool database. Statistical analysis was performed by SPSS® 18.0.ResultsData from 1433 patients with hepatitis C were evaluated. The mean patient age was 51.7 years (SD ± 10.7), and 50.6% were female. Direct-acting antivirals were prescribed for 345 (24.1%) patients, and a sustained virological response occurred in 264 (76.5%). The main comorbidities were systemic arterial hypertension [436 (30.4%)], diabetes mellitus [352 (24.6%)] and depression [130 (9.1%)]. The mean number of comorbidities was 1.52 (median [IQR] of 1.00 [1.00-2.00]). The mean number of comedications was 3.16 (median [IQR] of 3.00 [1.00-5.00]). A total of 12916 drug-drug interactions were found, of which 1.859 (14.4%) were high risk, with a mean of 1.29 ± 3.13 per patient. The 3D regimen, as well as glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir, presented the highest drug-drug interaction indexes.ConclusionComorbidities and comedications are common in patients with hepatitis C, as are drug-drug interactions. Even when second generation drugs are used, the occurrence of drug-drug interactions still presents a significant risk.

We explore what researchers can gain or lose by using three widely used models for the analysis of discrete choice experiment data-the random parameter logit (RPL) with correlated parameters, the RPL with uncorrelated parameters and the hybrid choice model. Specifically, we analyze three data sets focused on measuring preferences to support a renewable energy programme to grow seaweed for biogas production. In spite of the fact that all three models can converge to very similar median WTP values, they cannot be used indistinguishably. Each model is based on different assumptions, which should be tested before their use. The fact that standard sample sizes usually applied in environmental valuation are generally unable to capture the outcome differences between the models cannot be used as a justification for their indistinct application.

Photobiomodulation is a safe option for controlling pain, edema, and trismus when applied postoperatively in third molar surgery. However, administration prior to surgery has been under-explored. This study aims to explore the effectiveness of pre-emptive photobiomodulation in reducing postoperative edema in impacted lower third molar extractions. Two groups of healthy individuals undergoing tooth extraction will be randomly assigned: Control group receiving pre-emptive corticosteroid and simulated photobiomodulation, and Photobiomodulation Group receiving intraoral low-intensity laser and extraoral LED cluster application. The primary outcome will be postoperative edema after 48 h. The secondary outcomes will be pain, trismus dysphagia, and analgesic intake (paracetamol). These outcomes will be assessed at baseline as well as two and seven days after surgery. Adverse effects will be recorded. Data will be presented as means ± SD and a p-value < 0.05 will be indicative of statistical significance. [ABSTRACT FROM AUTHOR]

Objective: To analyze the perceptions of professionals, caregivers, children, and adolescents with disabilities regarding the implementation of the My Abilities First (MAF) tool in Specialized Child Rehabilitation Centers (CERs). Method: This is a qualitative research based on Reflexive Thematic Analysis (RTA). The study involved twenty-seven intentionally selected individuals, comprising 12 physiotherapists, 4 occupational therapists, 11 caregivers, 9 children and 2 adolescents. Participants completed sociodemographic and clinical questionnaires and took part in semi-structured online interviews, focusing on two themes: Positive health approaches and the MAF tool. The study was approved by the local ethics committee (opinion 4.779.175). Results: Reflexive Thematic Analysis of the interviews resulted in two themes: (1) Perceptions regarding the MAF tool as an educational and contributory process to enhance the inclusion and participation of children and adolescents with disabilities, and (2) Barriers and facilitators for the implementation process of the MAF tool. The implementation of MAF was identified as a driving factor in promoting equity and increased participation of children and adolescents with disabilities in various settings, including health, education, and leisure. Interviewees highlighted the need to confront attitudinal, communication, and social barriers that may hinder the implementation of the tool. Conclusion: The implementation of the MAF tool was perceived as an innovation due to its focus on the abilities of individuals with disabilities. However, there is a need to restructure it to broaden its scope and access to different contexts in order to confront barriers and enhance the inclusion and participation of children and adolescents with disabilities. [ABSTRACT FROM AUTHOR]

Oceans absorb a huge part of the atmospheric heat, leading to the rise in water temperature. Reefs are among the most affected ecosystems, where the complex behavioral repertoire of fishes is usually an indicator of environmental impacts. Here, we examined whether temperature (28 and 34°C) and habitat complexity (high and low) interact to affect the agonistic behavior (mirror test) of the dusky damselfish (Stegastes fuscus), a key species in Brazilian reefs because of its gardening capacity and territorial behavior. Higher temperatures altered basal behavior in both high and low-complexity conditions. Fish kept at 28°C under the high-complexity condition were more aggressive than those at a higher temperature (34°C) and in a low-complexity condition, which also exhibited lower dispersion. Our data show that changes in behavior of coral reef fish is associated to fluctuations in environmental conditions. Thus, it is important to implement management or conservation strategies that could mitigate global change effects.

[This corrects the article DOI: 10.1371/journal.pone.0233237.].

Alongside government driven management initiatives to achieve sustainable fisheries management, there remains a role for market-based mechanisms to improve fisheries outcomes. Market-based mechanisms are intended to create positive economic incentives that improve the status and management of fisheries. Research to understand consumer demand for certified fish is central but needs to be mirrored by supply side understanding including why fisheries decide to gain or retain certification and the impact of certification on them and other stakeholders involved. We apply semi-structured interviews in seven different Marine Stewardship Council (MSC) certified fisheries that operate in (or from) Western Australia with the aim of better understanding fisheries sector participation in certification schemes (the supply side) and the impacts and unintended benefits and costs of certification. We find that any positive economic impacts of certification were only realised in a limited number of MSC fisheries in Western Australia, which may be explained by the fact that only a small proportion of Western Australian state-managed fisheries are sold with the MSC label and ex-vessel or consumer market price premiums are therefore mostly not obtained. Positive impacts of certification in these Western Australian fisheries are more of a social and institutional nature, for example, greater social acceptability and increased efficiency in the governance process respectively. However, opinion is divided on whether the combined non-monetary and monetary benefits outweigh the costs.

Uveal melanoma (UM) is the most common primary intraocular cancer in adults. In the present study, we aimed to characterize the immunological features of primary UM cancer and to provide an association with prognostic markers and outcome. Also, we assessed the influence of the microenvironment on the expression of inhibitory immune checkpoints in UM. Genes of interest included MHC Class I and Class II molecules, as well as inhibitory immune-checkpoints, i.e. PDL1, PDL2, B7-H3, B7-H4, TBFRSF6B, CD47, CD155, GAL9, HVEM and CD200. We observed significant lower levels of MHC genes in UM cells as compared to normal uveal melanocytes. Unexpectedly however, the expression levels of most of the analyzed inhibitory immune-checkpoint genes were not different in cancer cells as compared to normal melanocytes, with the exception of CD200 and HVEM, that resulted significantly reduced. On the other hand, PDL1 inversely correlated with OS, PFS and thickness of the tumor. Also, PDL1, along with PDL2, expression significantly increased under inflammatory conditions. Finally, for the first time, we propose a possible role for CD47 in the immune evasive properties of UM. We show here that CD47 is significantly upregulated by UM cells following inflammatory stimuli and that it represents a good independent predictor of disease progression. The results from this study may propel advances in the development of immune-based therapies for UM patients.

BackgroundThough several procedures of IOL implantation have been described (sutured scleral fixation, intra-scleral fixation, angle-supported anterior chamber, and anterior chamber or retropupillary iris-claw IOLs), there are no randomized trials which are comparing different techniques. Hence, the surgical treatment of aphakia still remains controversial and challenging. The purpose of this study was to compare the long-term efficacy and the rate of complications of anterior versus posterior Iris-claw intraocular lenses (IOL) implantation to correct for the treatment of aphakia without sufficient capsule support.Methods and findingsConsecutive eyes having secondary implantation of aphakic iris-fixated IOLs with a follow-up of at least 5 years were considered. Mean correct distance visual acuity (CDVA) changes, percentage of eyes with CDVA improvement, mean corneal endothelial cell density (CECD) loss and the rate of other complications were used for statistical analysis. The study evaluated a total of 180 eyes (Group A: 87 anterior chamber iris-claw fixation, Group B: 93 retropupillary iris-claw implantation) of 180 consecutive different patients, with aphakia of various reasons. CDVA improved significantly in both groups after surgery (PConclusionsFive-year follow-up shows that secondary implantation of aphakic IOLs is effective and safe for the correction treatment of aphakia in eyes without capsule support.