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The COVID-19 pandemic-and its associated restrictions-have changed many behaviors that can influence environmental exposures including chemicals found in commercial products, packaging and those resulting from pollution. The pandemic also constitutes a stressful life event, leading to symptoms of acute traumatic stress. Data indicate that the combination of environmental exposure and psychological stress jointly contribute to adverse child health outcomes. Within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort, a national consortium initiated to understand the effects of environmental exposures on child health and development, our objective was to assess whether there were pandemic-related changes in behavior that may be associated with environmental exposures. A total of 1535 participants from nine cohorts completed a survey via RedCap from December 2020 through May 2021. The questionnaire identified behavioral changes associated with the COVID-19 pandemic in expected directions, providing evidence of construct validity. Behavior changes reported by at least a quarter of the respondents include eating less fast food and using fewer ultra-processed foods, hair products, and cosmetics. At least a quarter of respondents reported eating more home cooked meals and using more antibacterial soaps, liquid soaps, hand sanitizers, antibacterial and bleach cleaners. Most frequent predictors of behavior change included Hispanic ethnicity and older age (35 years and older). Respondents experiencing greater COVID-related stress altered their behaviors more than those not reporting stress. These findings highlight that behavior change associated with the pandemic, and pandemic-related psychological stress often co-occur. Thus, prevention strategies and campaigns that limit environmental exposures, support stress reduction, and facilitate behavioral change may lead to the largest health benefits in the context of a pandemic. Analyzing biomarker data in these participants will be helpful to determine if behavior changes reported associate with measured changes in exposure.

Familial Dysautonomia (FD) is a rare disease caused by ELP1 exon 20 skipping. Here we clarify the role of RNA Polymerase II (RNAPII) and chromatin on this splicing event. A slow RNAPII mutant and chromatin-modifying chemicals that reduce the rate of RNAPII elongation induce exon skipping whereas chemicals that create a more relaxed chromatin exon inclusion. In the brain of a mouse transgenic for the human FD-ELP1 we observed on this gene an age-dependent decrease in the RNAPII density profile that was most pronounced on the alternative exon, a robust increase in the repressive marks H3K27me3 and H3K9me3 and a decrease of H3K27Ac, together with a progressive reduction in ELP1 exon 20 inclusion level. In HEK 293T cells, selective drug-induced demethylation of H3K27 increased RNAPII elongation on ELP1 and SMN2, promoted the inclusion of the corresponding alternative exons, and, by RNA-sequencing analysis, induced changes in several alternative splicing events. These data suggest a co-transcriptional model of splicing regulation in which age-dependent changes in H3K27me3/Ac modify the rate of RNAPII elongation and affect processing of ELP1 alternative exon 20.

This paper presents an analysis on information disorder in social media platforms. The study employed methods such as Natural Language Processing, Topic Modeling, and Knowledge Graph building to gain new insights into the phenomenon of fake news and its impact on critical thinking and knowledge management. The analysis focused on four research questions: 1) the distribution of misinformation, disinformation, and malinformation across different platforms; 2) recurring themes in fake news and their visibility; 3) the role of artificial intelligence as an authoritative and/or spreader agent; and 4) strategies for combating information disorder. The role of AI was highlighted, both as a tool for fact-checking and building truthiness identification bots, and as a potential amplifier of false narratives. Strategies proposed for combating information disorder include improving digital literacy skills and promoting critical thinking among social media users.

BackgroundHuman Endogenous Retroviruses (HERVs) are fossil viruses that composes 8% of the human genome and plays several important roles in human physiology, including muscle repair/myogenesis. It is believed that inflammation may also regulate HERV expression, and therefore may contribute in the muscle repair, especially after training exercise. Hence, this study aimed to assess the level of HERVs expression and inflammation profile in practitioners' resistance exercises after an acute strength training session.MethodsHealthy volunteers were separated in regular practitioners of resistance exercise training group (REG, n = 27) and non-trained individuals (Control Group, n = 20). All individuals performed a strength exercise section. Blood samples were collected before the exercise (T0) and 45 minutes after the training session (T1). HERV-K (HML1-10) and W were relatively quantified, cytokine concentration and circulating microparticles were assessed.ResultsREG presented higher level of HERV-W expression (~2.5 fold change) than CG at T1 (pConclusionREG individuals exhibited a significant upregulation of HERV-W and modulation of inflammatory markers when compared to CG. This combined effect could potentially support the process of skeletal muscle repair in the exercised individuals.

Branching morphogenesis is a complex process shared by many organs including the lungs, kidney, prostate, as well as several exocrine organs including the salivary, mammary and lacrimal glands. This critical developmental program ensures the expansion of an organ's surface area thereby maximizing processes of cellular secretion or absorption. It is guided by reciprocal signaling from the epithelial and mesenchymal cells. While signaling pathways driving salivary gland branching morphogenesis have been relatively well-studied, our understanding of the underlying transcriptional regulatory mechanisms directing this program, is limited. Here, we performed in vivo and ex vivo studies of the embryonic mouse submandibular gland to determine the function of the transcription factor ΔNp63, in directing branching morphogenesis. Our studies show that loss of ΔNp63 results in alterations in the differentiation program of the ductal cells which is accompanied by a dramatic reduction in branching morphogenesis that is mediated by dysregulation of WNT signaling. We show that ΔNp63 modulates WNT signaling to promote branching morphogenesis by directly regulating Sfrp1 expression. Collectively, our findings have revealed a novel role for ΔNp63 in the regulation of this critical process and offers a better understanding of the transcriptional networks involved in branching morphogenesis.

IntroductionWorldwide, demographic ageing is a major social, economic and health challenge. Despite the increase in life expectancy, elderly often live with multiple chronic conditions, exposing them to multiple medications. Concerns have been raised about the growing issue of inappropriate long-term usage of proton-pump inhibitors (PPI), which have been associated with adverse outcomes and increased healthcare costs. Deprescribing is a recommended intervention to reduce or withdraw medicines that might be causing harm or might no longer be of benefit. This protocol details a trial to assess the effectiveness and cost-effectiveness of a collaborative deprescribing intervention of PPI among community-dwelling elderly, involving community pharmacists and general practitioners.Methods and analysisA pragmatic, multicentre, two-arm, non-randomised controlled trial of a structured PPI collaborative deprescribing intervention in the primary care setting with a 6-month follow-up will be conducted. Patients must be 65 years old or older, live in the community and have been using PPI for more than 8 weeks. We hypothesize that the intervention will reduce the PPI usage in the intervention group compared to the control group. The primary outcome is the successful discontinuation or dose decrease of any PPI, defined as a statistically significant absolute 20% reduction in medication use between the intervention and control groups at 3- and 6-month follow-ups. An economic evaluation will be conducted alongside the trial. This study was approved by the Ethics Research Committee of Nova Medical School, NOVA University of Lisbon and by the Ethics Committee from the Local Health Unit Alto Minho, Portugal.DiscussionThis pragmatic trial will provide evidence on the effectiveness and cost-effectiveness of a patient-centred collaborative deprescribing intervention in the community setting in Portugal. It will also inform improvements for the development of future multi-faceted interventions that aim to optimise medication for the community-dwelling elderly.Clinical trial registrationISRCTN 49637686.

[This corrects the article DOI: 10.1371/journal.pone.0282748.].

BackgroundTransvenous laser lead extraction (TLE) for cardiac implantable electric devices (CIED) is a challenging procedure especially if performed in octogenarians. In this study we evaluated the safety and efficacy of transvenous laser lead extraction in elderly patients.MethodsThis is a retrospective study of octogenarian patients who underwent laser-assisted lead extraction (LLE) (GlideLight laser sheath, Philips, San Diego, USA). 270 Consecutive patients were included. Patients were divided into two groups. Octogenarian group and non-octogenarian group. The Data was gathered from patients treated between September 2013 and January 2020 and is retrospectively analyzed.ResultsOf 270 consecutive patients, 38 (14.0%) were 80 years old or more. The total number of the extracted leads was 556 among which 84(15.0%) from the Octogenarian group. From these leads were 155 single coil leads, 82 dual coil leads, 129 right ventricular pacing leads, 155 right atrial leads, and 35 left ventricular leads. In the Octogenarian group the number of removed leads was as follows: 13 single coil leads, 10 dual coil leads, 28 right ventricular pacing leads, 28 right atrial leads and 5 left ventricular leads. No mortality was recorded in the Octogenarian group. One patient in the YG suffered from a superior vena cava tear and one patient suffered from pulmonary embolism.ConclusionIn octogenarian laser assisted lead extraction patients is a safe and effective procedure. No increase in morbidity, mortality or perioperative complication could be recorded in this group. Age should not be a limiting factor to perform this procedure.

Childhood obesity is a global public health concern linked to metabolic and psychological comorbidities. There is growing evidence that children's lifestyle habits are shifting towards obesity, with dire consequences for their future well-being and healthcare costs. In this interventional study, we enrolled 115 children aged between 4-5 years (53% females and 47% males) and carried out nutrition education interventions to improve their dietary habits. We introduced "Nutripiatto", a visual plate icon and easy guide, which was used by the children during the study. We investigated the children's dietary habits using a Food Frequency Questionnaire at the beginning and end of the study, after one month of using "Nutripiatto". The results showed that the children significantly increased the portion sizes and frequency of vegetable consumption (P

The COVID-19 pandemic-and its associated restrictions-have changed many behaviors that can influence environmental exposures including chemicals found in commercial products, packaging and those resulting from pollution. The pandemic also constitutes a stressful life event, leading to symptoms of acute traumatic stress. Data indicate that the combination of environmental exposure and psychological stress jointly contribute to adverse child health outcomes. Within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort, a national consortium initiated to understand the effects of environmental exposures on child health and development, our objective was to assess whether there were pandemic-related changes in behavior that may be associated with environmental exposures. A total of 1535 participants from nine cohorts completed a survey via RedCap from December 2020 through May 2021. The questionnaire identified behavioral changes associated with the COVID-19 pandemic in expected directions, providing evidence of construct validity. Behavior changes reported by at least a quarter of the respondents include eating less fast food and using fewer ultra-processed foods, hair products, and cosmetics. At least a quarter of respondents reported eating more home cooked meals and using more antibacterial soaps, liquid soaps, hand sanitizers, antibacterial and bleach cleaners. Most frequent predictors of behavior change included Hispanic ethnicity and older age (35 years and older). Respondents experiencing greater COVID-related stress altered their behaviors more than those not reporting stress. These findings highlight that behavior change associated with the pandemic, and pandemic-related psychological stress often co-occur. Thus, prevention strategies and campaigns that limit environmental exposures, support stress reduction, and facilitate behavioral change may lead to the largest health benefits in the context of a pandemic. Analyzing biomarker data in these participants will be helpful to determine if behavior changes reported associate with measured changes in exposure.

Immune and endocrine responses play a critical role in allowing animals to adjust to environmental perturbations. We measured immune and endocrine related markers in multiple samples from individuals from two managed-care care dolphin groups (n = 82 samples from 17 dolphins and single samples collected from two wild dolphin populations: Indian River Lagoon, (IRL) FL (n = 26); and Charleston, (CHS) SC (n = 19). The immune systems of wild dolphins were more upregulated than those of managed-care-dolphins as shown by higher concentrations of IgG and increases in lysozyme, NK cell function, pathogen antibody titers and leukocyte cytokine transcript levels. Collectively, managed-care care dolphins had significantly lower levels of transcripts encoding pro-inflammatory cytokine TNF, anti-viral MX1 and INFα and regulatory IL-10. IL-2Rα and CD69, markers of lymphocyte activation, were both lower in managed-care care dolphins. IL-4, a cytokine associated with TH2 activity, was lower in managed-care care dolphins compared to the free-ranging dolphins. Differences in immune parameters appear to reflect the environmental conditions under which these four dolphin populations live which vary widely in temperature, nutrition, veterinary care, pathogen/contaminant exposures, etc. Many of the differences found were consistent with reduced pathogenic antigenic stimulation in managed-care care dolphins compared to wild dolphins. Managed-care care dolphins had relatively low TH2 lymphocyte activity and fewer circulating eosinophils compared to wild dolphins. Both of these immunologic parameters are associated with exposure to helminth parasites which is uncommon in managed-care care dolphins. Less consistent trends were observed in a suite of hormones but significant differences were found for cortisol, ACTH, total T4, free T3, and epinephrine. While the underlying mechanisms are likely multiple and complex, the marked differences observed in the immune and endocrine systems of wild and managed-care care dolphins appear to be shaped by their environment.

Familial Dysautonomia (FD) is a rare disease caused by ELP1 exon 20 skipping. Here we clarify the role of RNA Polymerase II (RNAPII) and chromatin on this splicing event. A slow RNAPII mutant and chromatin-modifying chemicals that reduce the rate of RNAPII elongation induce exon skipping whereas chemicals that create a more relaxed chromatin exon inclusion. In the brain of a mouse transgenic for the human FD-ELP1 we observed on this gene an age-dependent decrease in the RNAPII density profile that was most pronounced on the alternative exon, a robust increase in the repressive marks H3K27me3 and H3K9me3 and a decrease of H3K27Ac, together with a progressive reduction in ELP1 exon 20 inclusion level. In HEK 293T cells, selective drug-induced demethylation of H3K27 increased RNAPII elongation on ELP1 and SMN2, promoted the inclusion of the corresponding alternative exons, and, by RNA-sequencing analysis, induced changes in several alternative splicing events. These data suggest a co-transcriptional model of splicing regulation in which age-dependent changes in H3K27me3/Ac modify the rate of RNAPII elongation and affect processing of ELP1 alternative exon 20. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of essential oils plus dry herbs (PHYTO) and encapsulated sodium butyrate (BUT) supplementation compared with enramycin (ENR), as a growth promoter, on the performance, diarrhoea control and intestinal microbiota in lightly weaned piglets. Two hundred weaned piglets, 20 days old, 4.69 ± 0.56 kg, were submitted during the nursery phase (20 to 69 days of age) to four treatments: control (CTR)-without any additive supplementation; ENR (with 8 ppm of enramycin throughout), BUT (with 2000 ppm between 20 to 34 d, 1500 ppm between 34 to 48 d and 1000 ppm between 48 to 69 d), and PHYTO (150 ppm between 20 to 48 d). At 62 days old, forty piglets (10 replicates per treatment) were slaughtered to perform bacterial identification through 16S rRNA (V3-V4) sequencing of the caecal content. During the second phase of the trial (34 to 48 days), the BUT group showed higher DWG (P = 0.023) and BW (P = 0.039) than the CTR group, and all groups that received additives had better FCR than the CTR group (P = 0.001). In the last phase of the trial (48 to 69 days), the ENR group presented a better FCR (P = 0.054) than the CRT and other groups. In the total period (20 to 69 days), ENR and BUT showed better FCR (P = 0.006) than CRT. Diarrhoea incident data showed differences (P

We propose a framework to analyse partisan debates that involves extracting, classifying and exploring the latent argumentation structure and dynamics of online societal controversies. In this paper, the focus is placed on causal arguments, and the proposed framework is applied to the Twitter debate on the consequences of a hard Brexit scenario. Regular expressions based on causative verbs, structural topic modelling, and dynamic time warping techniques were used to identify partisan faction arguments, as well as their relations, and to infer agenda-setting dynamics. The results highlight that the arguments employed by partisan factions are mostly constructed around constellations of effect-classes based on polarised verb groups. These constellations show that the no-deal debate hinges on structurally balanced building blocks. Brexiteers focus more on arguments related to greenfield trading opportunities and increased autonomy, whereas Remainers argue more about what a no-deal Brexit could destroy, focusing on hard border issues, social tensions in Ireland and Scotland and other economy- and healthcare-related problems. More notably, inferred debate leadership dynamics show that, despite their different usage of terms and arguments, the two factions' argumentation dynamics are strongly intertwined. Moreover, the identified periods in which agenda-setting roles change are linked to major events, such as extensions, elections and the Yellowhammer plan leak, and to new issues that emerged in relation to these events.

BackgroundAttention Deficit/Hyperactivity Disorder (ADHD) is associated with a diversity of impairments and Oppositional Defiant Disorder (ODD) is a very frequent comorbidity. Parent Training, as an evidence-based intervention, seems effective in reducing externalizing/disruptive behaviors, possibly leading to a better prognosis. This clinical trial aims to evaluate the effectiveness of an online parent training model as a complementary treatment for ADHD and ODD.MethodsPatients and their families will be screened upon their entry into the Research Center of Impulsivity and Attention (NITIDA) at UFMG-Brazil. Ninety families whose children are male, between 6-12 years old, and have significant externalizing symptoms and whose primary caregiver have complete high school education will be invited to participate. Families will be randomized (1:1) into 03 groups: 1) standard care; 2) standard care + face-to-face parent training; 3) standard care + online parent training. Interventions are analogous, differing only in delivery format. In the face-to-face format, the intervention will be conducted by a specialized therapist and the online format will be carried out through a platform. There will be six sessions/modules, arranged on a weekly basis. Measures of externalizing symptoms, parental and children quality of life, parental stress and parenting style will be collected at baseline and after the intervention.DiscussionThis clinical trial intends to verify the effects of a new, online, model of an evidence-based intervention, which would allow a wider access in the Brazilian context.Trial registrationRegistered on Brazilian Registry of Clinical Trials (ReBEC). Number: RBR-6cvc85. July 24th (2020) 05:35 pm.

BackgroundObesity is a growing problem worldwide, especially in countries with improved socioeconomic circumstances. Also, in the Netherlands the incidence of overweight and obesity is rising. There is increasing evidence on the association between obesity and tumorigenesis. Of all cancer types, endometrial cancer (EC) has the strongest positive correlation with obesity. Obesity is generally defined as a body mass index (BMI) >30, yet does not cover the differences in fat distribution in visceral and subcutaneous compartments. Visceral fat is assumed to be relatively more metabolically active and likely negative prognostic biomarker in non-endometrioid EC. Whereas subcutaneous fat is mainly responsible for oestrogen production through increased aromatase activity.ObjectiveThe aim of this study is to compare hormone levels and inflammatory markers after bilateral salpingo-oophorectomy (BSO) in obese and non-obese patients. Secondary objectives are to compare the effect of fat distribution and diagnosis (benign vs. EC) on the observed changes in hormone levels and inflammatory markers, and to compare the effect of BSO on menopausal complaints.MethodsProspective multicentre observational cohort study. A total of 160 patients will be included, of which 80 patients with a normal BMI (18-25 kg/m2) and 80 patients with an obese BMI >32-35 kg/m2. Preoperative abdominal CT will be performed and fasting venous blood samples are obtained for hormone levels and inflammation markers analysis. During surgery, adipose tissue biopsies of subcutaneous and visceral (omental and intestinal epiploic fat) compartments will be collected and stored fresh frozen. In addition a fasting blood draw six weeks after surgery will be obtained. All subjects will fill in two questionnaires before surgery and one after surgery.DiscussionWe hypothesize that BMI, the type of fat distribution, and possibly the underlying pathology significantly influence in hormone levels, and systemic inflammation changes after BSO. Previous studies have found several clues for a relationship between obesity and endometrial cancer. We expect that our study will contribute to pinpoint the exact differences between 'healthy obesity' and 'unhealthy obesity' and will help to identify patients that are more at risk of developing cancer (or possibly suffer from other related problems such as cardiovascular problems e.g.).

Extracellular matrix (ECM) is a fundamental component of the heart, guiding vital cellular processes during organ homeostasis. Most cardiovascular diseases lead to a remarkable remodeling of the ECM, accompanied by the formation of a fibrotic tissue that heavily compromises the heart function. Effective therapies for managing fibrosis and promoting physiological ECM repair are not yet available. The production of a decellularized extracellular matrix (d-ECM) serving as a three-dimensional and bioactive scaffold able to modulate cellular behavior and activities is considered crucial to achieve a successful regeneration. The protocol represents a step-by-step method to obtain a decellularized cardiac matrix through the combination of sodium dodecyl sulphate (SDS) and Triton X-100. Briefly, cardiac samples obtained from left ventricles of explanted, pathological human hearts were dissected and washed to remove residual body fluids. Samples were then snap-frozen and sliced by a cryostat into 350 μm thick sections. The sections obtained were decellularized using a solution containing 1% Triton X-100 and 1% SDS in combination, for 24 hours, until observing the color change from brownish-red to translucent-white. As a result, the protocol shows efficiency in preserving ECM architecture and protein composition during the whole process, suggesting that it is worthwhile, highly reproducible and produces a well- preserved decellularized extracellular matrix from cardiac samples. Notwithstanding, some limitations need to be addressed, such as the risk for microbial contamination and the unpredictable trend of the protocol when applied to decellularize samples other than myocardium, vessels, or skin. These issues require antibiotics mixture supplement during the procedure followed by UV sterilization, and appropriate adjustments for a tissue-specific utilization, respectively. The protocol is intended to produce a cardiac d-ECM for cell settlement, representing the ideal scaffold for tissue engineering purposes.

Purpose Obstructive sleep apnea (OSA) is a common, prevalent, and underdiagnosed disorder. Its lack of diagnosis and treatment is associated with increased morbidity and mortality. Previous screening questionnaires investigated parameters including body mass index, age, neck circumference, and sex, in addition to symptoms. This study aimed to validate a new Italian, self-administered, and easy-to-use six-item questionnaire that evaluates only subjective symptoms. Patients and methods The present study included 2622 patients (male, 2011; female, 611). Patients who were at least 18 years old, spoke Italian, referred to our sleep clinic for possible OSA, and completed the self-administered SANReSP questionnaire were recruited for the study. The predictive performance of the questionnaire was also evaluated. Results Nocturnal study showed 89.9% of OSA patients had apnea-hypopnea index (AHI) ≥ 5/h; 68.7%, AHI ≥ 15/h; and 48.2%, AHI ≥ 30/h. The optimal SANReSP score for AHI ≥ 5/h was >3 with a sensitivity and specificity of 74.76% and 67.92%, respectively, and an area under receiver operating characteristic curve (ROC) of 0.76. For moderate–severe OSA, the optimal SANReSP score was >3 (sensitivity, 78.18%; specificity, 46.53%; ROC, 0.66). For severe OSA, the optimal SANReSP score was >4 (sensitivity, 59.10%; specificity, 64.73%; ROC, 0.65). The probability of OSA increased with higher SANReSP scores (98.7% and 97.9% in men and women, respectively). Conclusion The SANReSP questionnaire is a short, easy-to-use, and self-administered screening tool for OSA. Its performance is similar to that of other widely used questionnaires; furthermore, it is advantageous in that it does not require anthropometric measurements.

We aimed to assess the feasibility of TESTA’T COVID strategy among healthcare and education professionals.in Spain during the peak of the 6th wave caused by Omicron variant. Kits were ordered online and sent by mail, participants answered an online acceptability/usability survey and uploaded the picture of results. 492 participants ordered a test, 304 uploaded the picture (61.8%). Eighteen positive cases were detected (5.9%). 92.2% were satisfied/very satisfied with the intervention; and 92.5% found performing the test easy/very easy. We demonstrated that implementing online COVID-19 self-testing in schools and healthcare settings in Spain is feasible.

The last year of Covid-19 pandemic has been characterized by the continuous chase between the vaccination campaign and the appearance of new variants that puts further obstacles to the possibility of eradicating the virus and returning to normality in a short period. In the present paper we develop a deterministic compartmental model to describe the evolution of the Covid-19 in Italy as a combined effect of vaccination campaign, new variant spreading and mobility restrictions. Particular attention is given to the mechanism of waning immunity, appropriately timed with respect to the effective progress of the vaccination campaign in Italy. We perform a retrospective analysis in order to explore the role that different mechanisms, such as behavioral changes, variation of the population mobility, seasonal variability of the virus infectivity, and spreading of new variants have had in shaping the epidemiological curve. We find that, in the large time window considered, the most relevant mechanism is the seasonal variation in the stability of the virus, followed by the awareness mechanism, that induces individuals to increase/relax self-protective measures when the number of active cases increases/decreases. The appearance of the Delta variant and the mobility variations have had instead only marginal effects. In absence of vaccines the emerging scenario would have been dramatic with a percentage difference in the number of total infections and total deaths, in both cases, larger than fifty per cent. The model also predicts the appearance of a more contagious variant (the Omicron variant) and its becoming dominant in January 2022.

In Malaysia, soil-transmitted helminth (STH) infections still persist among indigenous communities. In the past, local studies have focused mostly on epidemiologic aspects of STH infections with a scarcity of information on the efficacy of deworming treatment. The present study consisted of 2 phases: a cross-sectional phase on current epidemiological status and risk factors of STH infections and a longitudinal study over 6 weeks on triple dose albendazole efficacy against STH infections. A total of 253 participants were recruited at baseline and a pre-tested questionnaire was administered to obtain information on socio-demographics, environmental and behavioural risk factors. Stool samples were evaluated using a modified Kato-Katz technique. Cure rate (CR) and egg reduction rate (ERR) were assessed at 3 weeks following a 3-day course of 400mg albendazole treatment and infection status were observed again at 6 weeks. Baseline positivity of trichuriasis, ascariasis and hookworm infections were 56.1%, 11.9% and 20.2%, respectively. Multivariate analysis showed age below 18 years old (P = 0.004), without latrine in house (P = 0.042) and indiscriminate defecation (P = 0.032) were associated with STH infections. In the longitudinal study (N = 89), CR for trichuriasis was 64.6%, while CR of 100% was observed for both ascariasis and hookworm. ERR was above 90% for all three STH species. A rapid increased of Trichuris trichiura egg output was observed at 6 weeks. In conclusion, STH infections are highly prevalent among indigenous communities. Children and teenagers, poor sanitation and hygiene behaviour were determinants for STH infections. Triple dose albendazole is found to be efficacious against Ascaris lumbricoides and hookworm infections but has moderate curative effect with high ERR against T. trichiura. Although triple dose albendazole regimen has logistic challenges and may not be a routine option, consideration of this treatment regime may still be necessary in selective communities to reduce high intensity of T. trichiura infection.

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is used worldwide to test and trace the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). "Extraction-less" or "direct" real time-reverse transcription polymerase chain reaction (RT-PCR) is a transparent and accessible qualitative method for SARS-CoV-2 detection from nasopharyngeal or oral pharyngeal samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged 10 global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international interlaboratory ring trial. Participating laboratories were provided a common protocol, common reagents, aliquots of identical pooled clinical samples, and purified nucleic acids and used their existing in-house equipment. We observed 100% concordance across laboratories in the correct identification of all positive and negative samples, with highly similar cycle threshold values. The test also performed well when applied to locally collected patient nasopharyngeal samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that direct RT-PCR assay methods can be clearly translated across sites utilizing readily available equipment and expertise and are thus a feasible option for more efficient COVID-19 coronavirus disease testing as demanded by the continuing pandemic.

The regulation of energy balance involves an intricate interplay between neural mechanisms that respond to internal and external cues of energy demand and food availability. Compelling data have implicated the neurotransmitter dopamine as an important part of body weight regulation. However, the precise mechanisms through which dopamine regulates energy homeostasis remain poorly understood. Here, we investigate mechanisms through which dopamine modulates energy storage. We showed that dopamine signaling regulates fat reservoirs in Caenorhabditis elegans. We found that the fat reducing effects of dopamine were dependent on dopaminergic receptors and a set of fat oxidation enzymes. Our findings reveal an ancient role for dopaminergic regulation of fat and suggest that dopamine signaling elicits this outcome through cascades that ultimately mobilize peripheral fat depots.

This paper presents an analysis on information disorder in social media platforms. The study employed methods such as Natural Language Processing, Topic Modeling, and Knowledge Graph building to gain new insights into the phenomenon of fake news and its impact on critical thinking and knowledge management. The analysis focused on four research questions: 1) the distribution of misinformation, disinformation, and malinformation across different platforms; 2) recurring themes in fake news and their visibility; 3) the role of artificial intelligence as an authoritative and/or spreader agent; and 4) strategies for combating information disorder. The role of AI was highlighted, both as a tool for fact-checking and building truthiness identification bots, and as a potential amplifier of false narratives. Strategies proposed for combating information disorder include improving digital literacy skills and promoting critical thinking among social media users. [ABSTRACT FROM AUTHOR]

Background: Human Endogenous Retroviruses (HERVs) are fossil viruses that composes 8% of the human genome and plays several important roles in human physiology, including muscle repair/myogenesis. It is believed that inflammation may also regulate HERV expression, and therefore may contribute in the muscle repair, especially after training exercise. Hence, this study aimed to assess the level of HERVs expression and inflammation profile in practitioners' resistance exercises after an acute strength training session. Methods: Healthy volunteers were separated in regular practitioners of resistance exercise training group (REG, n = 27) and non-trained individuals (Control Group, n = 20). All individuals performed a strength exercise section. Blood samples were collected before the exercise (T0) and 45 minutes after the training session (T1). HERV-K (HML1-10) and W were relatively quantified, cytokine concentration and circulating microparticles were assessed. Results: REG presented higher level of HERV-W expression (~2.5 fold change) than CG at T1 (p<0.01). No difference was observed in the levels of HERV-K expression between the groups as well as the time points. Higher serum TNF-α and IL-10 levels were verified post-training session in REG and CG (p<0.01), and in REG was found a positive correlation between the levels of TNF-α at T1 and IL-10 at T0 (p = 0.01). Finally, a lower endothelial microparticle percentage was observed in REG at T1 than in T0 (p = 0.04). Conclusion: REG individuals exhibited a significant upregulation of HERV-W and modulation of inflammatory markers when compared to CG. This combined effect could potentially support the process of skeletal muscle repair in the exercised individuals. [ABSTRACT FROM AUTHOR]

PurposeTo introduce a novel method to quantitively analyse in three dimensions traction forces in a vast area of the ocular posterior pole.MethodsRetrospective analysis of 14 eyes who underwent peeling surgery for idiopathic, symptomatic and progressive epiretinal membrane. The technique measures the shift in position of vascular crossings after surgery from a fixed point, which is the retinal pigmented epithelium. This shift is defined as the relaxation index (RI) and represents a measure of the postoperative movement of the retina due to released traction after surgery.ResultsBest-corrected visual acuity was significantly better than baseline at all follow ups while the RI had its maximum value at baseline. Moreover, we found a significant correlation between best-corrected visual acuity at 6 months and RI at baseline.ConclusionWhile all previous published methods focused on bi-dimensional changes observed in a small region, this study introduces a three-dimensional assessment of tractional forces. Future integration of RI into built-in processing software will allow systematic three-dimensional measurement of intraretinal traction.

Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2-4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.

IntroductionDuring COVID-19 pandemic, the use of several drugs has represented the worldwide clinical practice. However, though the current increase of knowledge about the disease, there is still no effective treatment for the usage of drugs. Thus, we retrospectively assessed use and effects of therapeutic regimens in hospitalized patients on in-hospital mortality.MethodsCOVOCA is a retrospective observational cohort study on 18 COVID centres throughout Campania Region Hospitals. We included adult patients with confirmed SARS-CoV-2 infection, discharged/dead between March/June 2020.Results618 patients were included, with an overall in-hospital cumulative mortality incidence of 23.1%. Most prescribed early treatments were antivirals (72%), antibiotics (65%) and hydroxychloroquine/anticoagulants (≈50%). Tocilizumab, indeed, was largely prescribed late during hospitalization. Multivariable models, with a cut-off at day 2 for early COVID-19 therapy administration, did not disclose any significant association of a single drug administration on the clinical outcome.DiscussionCOVOCA represents the first multicenter database in Campania region. None drug class used during the pandemic significantly modified the outcome, regardless of therapy beginning, both overall and net of those already in non-invasive ventilation (NIV)/ orotracheal intubation (OTI) at hospitalization. Our cumulative incidence of mortality seems lower than other described during the same period, particularly in Northern Italy.

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms.

Multiple Sclerosis (MS) progresses at an unpredictable rate, but predictions on the disease course in each patient would be extremely useful to tailor therapy to the individual needs. We explore different machine learning (ML) approaches to predict whether a patient will shift from the initial Relapsing-Remitting (RR) to the Secondary Progressive (SP) form of the disease, using only "real world" data available in clinical routine. The clinical records of 1624 outpatients (207 in the SP phase) attending the MS service of Sant'Andrea hospital, Rome, Italy, were used. Predictions at 180, 360 or 720 days from the last visit were obtained considering either the data of the last available visit (Visit-Oriented setting), comparing four classical ML methods (Random Forest, Support Vector Machine, K-Nearest Neighbours and AdaBoost) or the whole clinical history of each patient (History-Oriented setting), using a Recurrent Neural Network model, specifically designed for historical data. Missing values were handled by removing either all clinical records presenting at least one missing parameter (Feature-saving approach) or the 3 clinical parameters which contained missing values (Record-saving approach). The performances of the classifiers were rated using common indicators, such as Recall (or Sensitivity) and Precision (or Positive predictive value). In the visit-oriented setting, the Record-saving approach yielded Recall values from 70% to 100%, but low Precision (5% to 10%), which however increased to 50% when considering only predictions for which the model returned a probability above a given "confidence threshold". For the History-oriented setting, both indicators increased as prediction time lengthened, reaching values of 67% (Recall) and 42% (Precision) at 720 days. We show how "real world" data can be effectively used to forecast the evolution of MS, leading to high Recall values and propose innovative approaches to improve Precision towards clinically useful values.

Complement is a key component of the innate immune system. Inappropriate complement activation underlies the pathophysiology of a variety of diseases. Complement component 5 (C5) is a validated therapeutic target for complement-mediated diseases, but the development of new therapeutics has been limited by a paucity of preclinical models to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) properties of candidate therapies. The present report describes a novel humanized C5 mouse and its utility in evaluating a panel of fully human anti-C5 antibodies. Surprisingly, humanized C5 mice revealed marked differences in clearance rates amongst a panel of anti-C5 antibodies. One antibody, pozelimab (REGN3918), bound C5 and C5 variants with high affinity and potently blocked complement-mediated hemolysis in vitro. In studies conducted in both humanized C5 mice and cynomolgus monkeys, pozelimab demonstrated prolonged PK and durable suppression of hemolytic activity ex vivo. In humanized C5 mice, a switch in dosing from in-house eculizumab to pozelimab was associated with normalization of serum C5 concentrations, sustained suppression of hemolytic activity ex vivo, and no overt toxicity. Our findings demonstrate the value of humanized C5 mice in identifying new therapeutic candidates and treatment options for complement-mediated diseases.

Management practices such as tillage, crop rotation, irrigation, organic and inorganic inputs application are known to influence diversity and function of soil microbial populations. In this study, we investigated the effect of conventional versus organic farming systems at low and high input levels on structure and diversity of prokaryotic microbial communities. Soil samples were collected from the ongoing long-term farming system comparison trials established in 2007 at Chuka and Thika in Kenya. Physicochemical parameters for each sample were analyzed. Total DNA and RNA amplicons of variable region (V4-V7) of the 16S rRNA gene were generated on an Illumina platform using the manufacturer's instructions. Diversity indices and statistical analysis were done using QIIME2 and R packages, respectively. A total of 29,778,886 high quality reads were obtained and assigned to 16,176 OTUs at 97% genetic distance across both 16S rDNA and 16S rRNA cDNA datasets. The results pointed out a histrionic difference in OTUs based on 16S rDNA and 16S rRNA cDNA. Precisely, while 16S rDNA clustered by site, 16S rRNA cDNA clustered by farming systems. In both sites and systems, dominant phylotypes were affiliated to phylum Actinobacteria, Proteobacteria and Acidobacteria. Conventional farming systems showed a higher species richness and diversity compared to organic farming systems, whilst 16S rRNA cDNA datasets were similar. Physiochemical factors were associated differently depending on rRNA and rDNA. Soil pH, electrical conductivity, organic carbon, nitrogen, potassium, aluminium, zinc, iron, boron and micro-aggregates showed a significant influence on the observed microbial diversity. The observed higher species diversity in the conventional farming systems can be attributed to the integration of synthetic and organic agricultural inputs. These results show that the type of inputs used in a farming system not only affect the soil chemistry but also the microbial population dynamics and eventually the functional roles of these microbes.

The research objective was to study the presence of DNA damages in haddock exposed to petrogenic or pyrogenic polyaromatic hydrocarbons (PAHs) from different sources: 1) extracts of oil produced water (PW), dominated by 2-ring PAHs; 2) distillation fractions of crude oil (representing oil-based drilling mud), dominated by 3-ring PAHs; 3) heavy pyrogenic PAHs, mixture of 4/5/6-ring PAHs. The biological effect of the different PAH sources was studied by feeding juvenile haddock with low doses of PAHs (0.3-0.7 mg PAH/kg fish/day) for two months, followed by a two-months recovery. In addition to the oral exposure, a group of fish was exposed to 12 single compounds of PAHs (4/5/6-ring) via intraperitoneal injection. The main endpoint was the analysis of hepatic and intestinal DNA adducts. In addition, PAH burden in liver, bile metabolites, gene and protein expression of CYP1A, GST activity, lipid peroxidation, skeletal deformities and histopathology of livers were evaluated. Juvenile haddock responded quickly to both intraperitoneal injection and oral exposure of 4/5/6-ring PAHs. High levels of DNA adducts were detected in livers three days after the dose of the single compound exposure. Fish had also high levels of DNA adducts in liver after being fed with extracts dominated by 2-ring PAHs (a PW exposure scenario) and 3-ring PAHs (simulating an oil exposure scenario). Elevated levels of DNA adducts were observed in the liver of all exposed groups after the 2 months of recovery. High levels of DNA adduct were found also in the intestines of individuals exposed to oil or heavy PAHs, but not in the PW or control groups. This suggests that the intestinal barrier is very important for detoxification of orally exposures of PAHs.

BackgroundVery elderly critically ill patients (ie, those older than 75 or 80 years) are an increasing population in intensive care units. However, patients with cancer have encompassed only a minority in epidemiological studies of very old critically-ill patients. We aimed to describe clinical characteristics and identify factors associated with hospital mortality in a cohort of patients aged 80 or older with cancer admitted to intensive care units (ICUs).MethodsThis was a retrospective cohort study in 94 ICUs in Brazil. We included patients aged 80 years or older with active cancer who had an unplanned admission. We performed a mixed effect logistic regression model to identify variables independently associated with hospital mortality.ResultsOf 4604 included patients, 1807 (39.2%) died in hospital. Solid metastatic (OR = 2.46; CI 95%, 2.01-3.00), hematological cancer (OR = 2.32; CI 95%, 1.75-3.09), moderate/severe performance status impairment (OR = 1.59; CI 95%, 1.33-1.90) and use of vasopressors (OR = 4.74; CI 95%, 3.88-5.79), mechanical ventilation (OR = 1.54; CI 95%, 1.25-1.89) and renal replacement (OR = 1.81; CI 95%, 1.29-2.55) therapy were independently associated with increased hospital mortality. Emergency surgical admissions were associated with lower mortality compared to medical admissions (OR = 0.71; CI 95%, 0.52-0.96).ConclusionsHospital mortality rate in very elderly critically ill patients with cancer with unplanned ICU admissions are lower than expected a priori. Cancer characteristics, performance status impairment and acute organ dysfunctions are associated with increased mortality.

BackgroundEndometriosis is a debilitating gynecologic disease characterized by the implantation of endometrial tissue in ectopic locations, with signs of severe and chronic inflammation. The new knowledge on endometriosis has highlighted the value of secondary prevention through the early diagnosis and treatment of lesions to reduce serious consequences, first of all, infertility and chronic pelvic pain. The purpose of this study is to assess the reliability and validity of the questionnaire, as a tool to precociously identify women with endometriosis, to prevent the progression of symptoms.MethodWe reviewed the literature and selected risk factors, symptoms, and phenotypic traits of the women affected by endometriosis to create the questionnaire divided into 8 modules, with 47 questions. A total of 151 women completed the questionnaires: 51 patients who have endometriosis (the cases) and 100 matched women without endometriosis (the controls). After data collection, bivariate and multivariate analyses were conducted.ResultsWe retained four of the significant variables from a step-down logistic regression, namely chronic pelvic pain, dyspareunia with VAS≥3, painful defecation, and acne, to develop a final "predictive" logistic model achieving 90.2% sensitivity and 75% specificity.ConclusionOur pilot study demonstrated that the questionnaire provides a powerful tool for the secondary prevention of endometriosis.

Novel Covid-19 has had a huge impact on the world's population since December 2019. The very rapid spreading of the virus worldwide, with its heavy toll of death and overload of the healthcare systems, induced the scientific community to focus on understanding, monitoring and foreseeing the epidemic evolution, weighing up the impact of different containment measures. An immense literature was produced in few months. Many papers were focused on predicting the peak features through a variety of different models. In the present paper, combining the surveillance data-set with data on mobility and testing, we develop a deterministic compartment model aimed at performing a retrospective analysis to understand the main modifications occurred to the characteristic parameters that regulate the epidemic spreading. We find that, besides self-protective behaviors, a reduction of susceptibility should have occurred in order to explain the fast descent of the epidemic after the peak. A sensitivity analysis of the basic reproduction number, in response to variations of the epidemiological parameters that can be influenced by policy-makers, shows the primary importance of a rigid isolation procedure for the diagnosed cases, combined with an intensive effort in performing extended testing campaigns. Future scenarios depend on the ability to protect the population from the injection of new cases from abroad, and to pursue in applying rigid self-protective measures.

BackgroundItaly has been the first Western country to be heavily affected by the spread of SARS-COV-2 infection and among the pioneers of the clinical management of pandemic. To improve the outcome, identification of patients at the highest risk seems mandatory.ObjectivesAim of this study is to identify comorbidities and clinical conditions upon admission associated with in-hospital mortality in several COVID Centers in Campania Region (Italy).MethodsCOVOCA is a multicentre retrospective observational cohort study, which involved 18 COVID Centers throughout Campania Region, Italy. Data were collected from patients who completed their hospitalization between March-June 2020. The endpoint was in-hospital mortality, assessed either from data at discharge or death certificate, whilst all exposure variables were collected at hospital admission.ResultsAmong 618 COVID-19 hospitalized patients included in the study, 143 in-hospital mortality events were recorded, with a cumulative incidence of about 23%. At multivariable logistic analysis, male sex (OR 2.63, 95%CI 1.42-4.90; p = 0.001), Chronic Liver Disease (OR 5.88, 95%CI 2.39-14.46; pConclusionMortality of patients hospitalized for COVID-19 appears strongly affected by both clinical conditions on admission and comorbidities. Originally, we observed a very poor outcome in subjects with a chronic liver disease, alongside with an increase of hepatic damage.

Current and foreseeable automated vehicles are not able to respond appropriately in all circumstances and require human monitoring. An experimental examination of steering automation failure shows that response latency, variability and corrective manoeuvring systematically depend on failure severity and the cognitive load of the driver. The results are formalised into a probabilistic predictive model of response latencies that accounts for failure severity, cognitive load and variability within and between drivers. The model predicts high rates of unsafe outcomes in plausible automation failure scenarios. These findings underline that understanding variability in failure responses is crucial for understanding outcomes in automation failures.

Despite physical activity being one of the determinants of healthy aging, older people tend to become less active over the years. Maintaining physical activity levels during the life course is a motivational challenge. Digital tools have been used to change this pattern, such as smartphone applications to support physical activity; but there is a lack of in-depth research on the diversity of user's experiences, especially considering older users or non-users of information and communication technologies.ObjectiveOur goal was to identify requirements for designing a mobile app to encourage physical activity in a low-income community population of older people in Brazil (i.e. over 40 years old).MethodWe conducted a qualitative focus group study, involving by co-design of a physical activity application (Pacer)®. Seventeen volunteers were divided into 2 focus groups of physical active and insufficiently active, and 2 further 4 subgroups in each characterised by digital engagement. The following procedures were performed: (i) baseline assessments; (ii) a focus group with physically active older people and a focus group with insufficiently active older people (iii) design activities with both groups to re-design Pacer.ResultsDeveloping physical activity apps for older people should consider the following features: free application, simple interface, motivational messages using audio and visual information, sharing information among users, multimedia input and sharing and user customisation. In particular, we recommend that exercise apps in low-income communities be tailored to our four categories of users differing in baseline physical activity and digital engagement, to match the social and behavioural preferences we discovered.