Search

Neonicotinoids, a highly effective class of insecticides used worldwide, have been identified as a major cause of concern for biodiversity. To assess the ecological and environmental consequences of neonicotinoids' use, reliable analytical methodologies, including calibration approaches, are needed. Here, we compared the performance of internal calibration (IC) using a single concentration of stable isotope-labeled standard (SIL) with classical multipoint external calibration (EC) for the quantification of six neonicotinoids in honey. IC showed acceptable levels of trueness (86.3% - 116.0%) and precision (1.4% - 20.8%), although slight biases were observed at very low concentrations compared to EC. When applied to 32 original honey samples, both approaches showed strong agreement (R2 > 0.998) with proportional biases lower than 5%. These results highlight the possibility of implementing IC to simplify quantification in liquid chromatography-mass spectrometry-based pesticide applications.

ABSTRACT: Objectives: The aim of this work was to analyse inequalities in oral health services utilisation (OHSU) in older Peruvian adults through comparative analysis of the years 2019 and 2021. Methods: We conducted a secondary analysis of data from the 2019 and 2021 Demographic and Health Survey (ENDES). The outcome variable was OHSU by older Peruvian adults in the past year. We used Poisson generalised linear models adjusted for age and sex to assess changes in OHSU by sociodemographic characteristics. The Erreygers concentration index was used to describe the socioeconomic inequalities in OHSU. The contribution of each variable to inequalities was estimated by a decomposition analysis. Results: In 2021, OHSU probability amongst older Peruvian adults decreased by 37% compared to 2019. The decline was greatest in those aged 80 or older (51%), the lowest wealth quintile (47%), those with functional limitations (53%), and those whose native language is Quechua or other indigenous languages (47%). Surprisingly, we observed a reduction in OHSU inequalities (difference: −0.1074; P = .003) during the COVID-19 pandemic, particularly amongst rural residents (difference: −0.0771; P = .030), the lowest wealth quintile (difference: −0.0764; P = .020), and those with functional limitations (difference: −0.3665; P < .001). Poverty accounted for 73% of the inequality in 2021. Conclusions: The probability of OHSU has significantly decreased likely due to the COVID-19 pandemic. Paradoxically, we observed a reduction in OHSU inequalities during the pandemic, despite the known socioeconomic impact. However, further research is required to gain deeper understanding of this phenomenon.

Tuberculosis (TB) poses a significant global public health challenge, particularly in developing countries. Over the years, scientific research has played a pivotal role in addressing this disease. In this study, we aimed to analyze and outline the trends in scientific output on TB and identify research priorities in Latin America (LA) from 1990 to 2021. Scientific production was analyzed, and the number of publications, financing sources, and journal characteristics were evaluated. Collaboration networks and keywords were visualized using mapping analysis with VOSviewer software. Research themes were prioritized by country based on co-occurrence frequency. In total, 4399 documents were identified, a significant trend was evident in the number of publications per year (R2 = 0.981), and research substantially contributed to the reduction of TB-related mortality (R2 = −0.876). Most publications were original articles (83.8 %). The International Journal of Tuberculosis and Lung Disease had the highest publication and citation rates per document. International collaboration was predominantly with the United States, France, and Canada. Brazil, Argentina, and Mexico had the highest number of publications and external collaborations. In LA, interest in researching studies related to treatment and diagnosis (32.5 %) was notably high, followed by epidemiology and screening (26.9 %). Among the 20 countries in LA, research priorities varied, with the highest emphasis on HIV/AIDS (14/20), epidemiology (9/20), anti-TB agents (6/20), and mortality (5/20). TB resistance was only considered a research priority in Brazil, Peru, and Haiti. Therefore, LA experienced significant growth in its scientific output, playing a crucial role in TB control. Strategic adaptation to the region's specific challenges was observed, particularly in HIV/AIDS coinfection, epidemiological studies, and drug resistance. This progress was achieved by outstanding international scientific collaboration. This holistic approach emphasizes the importance of research in the fight against TB in LA.

Summary: Chronic kidney disease (CKD) is a major public health burden, with dietary acid load (DAL) and gut microbiota playing crucial roles. As DAL can affect the host metabolome, potentially via the gut microbiota, we cross-sectionally investigated the interplay between DAL, host metabolome, gut microbiota, and early-stage CKD (TwinsUK, n = 1,453). DAL was positively associated with CKD stage G1-G2 (Beta (95% confidence interval) = 0.34 (0.007; 0.7), p = 0.046). After adjusting for covariates and multiple testing, we identified 15 serum, 14 urine, 8 stool, and 7 saliva metabolites, primarily lipids and amino acids, associated with both DAL and CKD progression. Of these, 8 serum, 2 urine, and one stool metabolites were found to mediate the DAL-CKD association. Furthermore, the stool metabolite 5-methylhexanoate (i7:0) correlated with 26 gut microbial species. Our findings emphasize the gut microbiota’s therapeutic potential in countering DAL’s impact on CKD through the host metabolome. Interventional and longitudinal studies are needed to establish causality.

Summary: Cardiometabolic diseases are leading causes of mortality in Western countries. Well-established risk factors include host genetics, lifestyle, diet, and the gut microbiome. Moreover, gut bacterial communities and their activities can be altered by bacteriophages (also known simply as phages), bacteria-infecting viruses, making these biological entities key regulators of human cardiometabolic health. The manipulation of bacterial populations by phages enables the possibility of using phages in the treatment of cardiometabolic diseases through phage therapy and fecal viral transplants. First, however, a deeper understanding of the role of the phageome in cardiometabolic diseases is required. In this review, we first introduce the phageome as a component of the gut microbiome and discuss fecal viral transplants and phage therapy in relation to cardiometabolic diseases. We then summarize the current state of phageome research in cardiometabolic diseases and propose how the phageome might indirectly influence cardiometabolic health through gut bacteria and their metabolites.

Objectives: The worldwide heart failure (HF) prevalence is 8.52 per 1000 inhabitants, with a global economic burden of 346.17 billion dollars. With the COVID-19 pandemic, the focus of medical care has changed to treating the morbidity and mortality of patients with COVID-19 and reducing medical procedures or visits to patients with HF, with the impact being greater in low- and middle-income countries. Methods: We performed an interrupted time series analysis of HF to determine the changes in the trend of hospitalizations and in-hospital mortality of HF patients before and after the mandatory lockdown in Peru. Results: A total of 18,514 adults were included in the analysis. Monthly hospital admissions immediately decreased by 599 (95% confidence interval [CI]: 113 to 1085) and the difference in slope before and after the lockdown was 6.4 hospital admissions (95% CI: −4 to 18). In-hospital mortality increased by 18% (95% CI: −8%–43%) and the difference in slope before and after the lockdown was −0.3% (95% CI: −0.9%–0.25%). Conclusions: There was a reduction in hospitalizations and an increase in the in-hospital mortality of patients with HF before and after the mandatory lockdown due to the COVID-19 pandemic in Peru.

The Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria aims to stratify patients undergoing percutaneous coronary intervention (PCI) and are now recommended by international guidelines to stratify bleeding risk in clinical practice. We searched electronic databases from 2019 (ARC-HBR proposal) up to February 2021 for studies that reported the occurrence of major bleedings according to ARC-HBR status in patients undergoing PCI and pooled them as relative risk (RR) in a random-effect analysis. Only studies that reported events according to the number of times the ARC-HBR definition was met were included in a sensitivity analysis and RR for each stratum was calculated. Nine studies and 68,874 subjects were included in our analysis; 39.2% of them were at HBR and they had a significantly higher risk of major bleedings (RR: 2.70; 95% CI: 2.35–3.10; p

Objective: The correction of functional mitral regurgitation (FMR) with transcatheter edge-to-edge repair (TEER) can favorably affect patients’ hemodynamic profile. However, the procedure requires inter-atrial trans-septal access and the hemodynamic relevance of the residual iatrogenic atrium septal defect (iASD) is still debated. This study aimed at investigating the hemodynamic modifications during TEER with MitraClip, before and after the iASD creation, in patients with heart failure with reduced ejection fraction (HFrEF) and severe FMR. Methods: Thirty-nine HFrEF patients with 3+ or 4+/4+ FMR were included. Right heart catheterization was performed at baseline after general anesthesia induction and at the end of TEER, both before and after removing the device guiding catheter. Results: Compared with baseline, MitraClip positioning was followed by a significant immediate improvement in cardiac output (respectively: 3.36 vs 5.05 ml/min), pulmonary artery wedge pressure (23.7 vs 18.2 mmHg), mean pulmonary artery pressure (34.4 vs 27.7 mmHg) and pulmonary vascular resistance (3.6 vs 2.2 Wood Units) (all p < 0.001). No further significant modifications occurred after removing the device guiding catheter. Conclusions: Our data suggest that the acute hemodynamic modifications after TEER are not influenced by the induction of iASD in patients with FMR.

Worldwide, Human T-lymphtropic virus-1 and 2 (HTLV-1 and 2) infects approximately more than 10 million people, mostly occurring in hyperendemic areas such as the region of Latin America and the Caribbean (LAC). A comprehensive bibliographic exploration of original articles published on the Web of Science Core Collection database over the last 10 years was done. A bibliometric analysis was performed using the bibliometrix package in RStudio and VOSviewer. A total of 519 articles published in 194 journals were identified along the 10 years studied. In 2012 the peak number of publications was identified and the average number of citations per document was 1.33. Galvao-Castro B was the author with the greatest number of publications. Aids Research and Human Retroviruses was the most productive journal, and the study by Bangham CRM was the most cited. Brazil was the country with most corresponding authors that had the most publications and the most significant number of total citations. Infections and HTLV-1 were the most used keywords. In conclusion, according to the current quantitative analysis, there is a need for more significant promotion of research on HTLV-1 and 2 among the scientific community of LAC.

Congenital atresia of the left main coronary artery is a rare coronary anomaly, in which the left coronary ostium is absent and the blood supply to the entire heart is provided by the right coronary artery. We show the images of the coronary CT angiography performed by a 56-year-old man, with evidence of this vascular abnormality. Coronary CT Angiography has gained a major role in coronary anomalies assessment, thank to high spatial and temporal resolution.

Summary: Background: Inflammation can modulate tumour growth and progression, and influence clinical response to treatment. We investigated the potential of circulating inflammatory proteins for response stratification of immune checkpoint inhibitor (ICI) therapy for advanced melanoma. Methods: Study subjects were 87 patients with unresectable stage III or IV cutaneous melanoma from the multiple centres across the United Kingdom (UK) and the Netherlands (NL) who received ipilimumab, nivolumab, or pembrolizumab, or a combination of ipilimumab and nivolumab. Serum samples were collected before and during ICI therapy at follow-up visits scheduled every third week over a 12-week period. We performed targeted quantification of 92 proteins involved in inflammation and tested for association of their pre-treatment and on-treatment levels, as well as longitudinal changes, with overall response rate, progression-free survival, and overall survival. Findings: We observed consistently higher pre-treatment levels of interleukin-6 (IL-6), hepatocyte growth factor (HGF), and monocyte chemotactic protein 2 (MCP-2), in non-responders compared to responders (meta-analysis p=3.31 × 10−4, 2.29 × 10−4, and 1.02 × 10−3, respectively). Patients' stratification according to the median value of IL-6, HGF, and MCP-2 highlighted a cumulative negative effect of pre-treatment levels of the three proteins on response (p=1.13 × 10−2), with overall response rate among patients presenting with combined elevated IL-6, HGF, and MCP-2 levels being three-fold lower (26.7%) compared to patients with none of the three proteins elevated (80.0%, p=9.22 × 10−3). Longitudinal data analysis showed that on-treatment changes in circulating inflammatory proteins are not correlated with response. Interpretation: Our findings are in line with an increasing body of evidence that the pro-inflammatory cytokine IL-6 can influence response to ICI in advanced melanoma, and further support a role of circulating HGF and MCP-2 levels as prognostic biomarkers as suggested by previous smaller studies. Inflammatory proteins may serve as predictive biomarkers of ICI response and valuable targets for combination therapy. Funding: This work was supported by the Seerave Foundation and Dutch Cancer Society.

Summary: Background: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection. Methods: This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose. Findings: 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p

Background: In March 2020, the Peruvian state introduced quarantine as a measure to control the spread of SARS-CoV-2. It has been suggested that being in quarantine is associated with the development of symptoms of Post-traumatic Stress Disorder (PTSD). The present study aims to explore the factors associated with the development of PTSD in a post-quarantine context due to COVID-19 in medical students. Objectives: To evaluate the factors associated with the development of post-quarantine PTSD symptoms in medical students from a Peruvian university. Methods: Analytical cross-sectional study. The objective will be developed after the lifting of the quarantine in Peru. Medical students enrolled during the 2020-01 academic cycle of the Peruvian University of Applied Sciences will be included. To collect the outcome variable (PTSD), the Impact of Event Scale - Revised (IES-R) will be used. The associated factors will be collected through a form that will be validated by experts and piloted in the field. The crude and adjusted coefficients will be calculated, using bivariate and multivariate linear regression models, respectively. We will use the “manual forward selection” technique to obtain a final model with minimally sufficient fit. After each model comparison and decision, multicollinearity will be evaluated with the variance inflation factor and matrix of independent variables. Results: Not having health insurance, having relatives or close friends who contracted the disease and having a lower family income are factors associated with PTSD in the post-quarantine context of the COVID-19 pandemic in medical students at a Peruvian university. Conclusions: Clinical evaluation is important for medical students with a high probability of having PTSD symptoms. We recommend conducting a longitudinal study to identify causality and other unstudied factors related to PTSD.

Fasciíte Necrosante (FN) é uma infecção grave de partes moles caracterizada por necrose rapidamente progressiva, difusa, da fáscia e dos tecidos adjacentes. Em tempos atuais, não existem dados exatos quanto a sua real incidência. Em relação aos casos de FN em mama sem associação com fatores de risco, menos de 20 casos foram descritos na literatura. Relato de Caso: G.C.R.C, sexo feminino, 19 anos, parda, solteira, natural e residente no Estado do Rio de Janeiro. Dá entrada no Pronto Socorro de um hospital público, em Volta Redonda, em fevereiro de 2021, referindo mastalgia e sinais flogísticos em mama direita, sem trauma ou ferida local preexistentes, associados a febre não termometrada há três dias. Notou-se piercing mamilar, implantado há dois anos, sendo retirado durante a abordagem inicial. Após esse procedimento, teve alta para casa e, após 12 horas, retornou ao hospital apresentando, ao exame físico, mama direita hiperemiada na região periareolar e irradiação lateral do processo inflamatório. No dia seguinte à admissão, foi internada no Setor de Ginecologia e Obstetrícia e, em quatro horas, evoluiu com equimose periareolar extensa, avançando com piora dos sinais flogísticos, flictemas de conteúdo serossanguinolento e necrose periareolar. Estipulou-se assim a hipótese diagnóstica de FN. No quarto dia de internação, foi submetida a amplo desbridamento cirúrgico com fasciotomia e retirada de todo tecido necrótico. Permaneceu em antibioticoterapia por 14 dias no Centro de Terapia Intensiva. O quadro ilustrava involução progressiva com redução de secreções seropurulentas e sinais inflamatórios. Após término do esquema antimicrobiano, recebeu alta hospitalar e foi mantida em acompanhamento ambulatorial para manutenção de curativos. No 35° dia após sua alta hospitalar, em abril, a paciente foi submetida a cirurgia plástica reparadora. Realizou-se enxerto de pele com área doadora da região infraumbilical. O procedimento ocorreu sem intercorrências, sendo finalizado com curativo de Brown. Esse é um dos poucos casos registrados de FN em mama, sendo necessários mais estudos quanto à sua patogênese, ao seu diagnóstico e ao seu tratamento para melhor manejo clínico.

Background: Exercise-induced muscle damage (EIMD) commonly occurs following intense resistance exercise and is associated with decrements in exercise performance and delayed muscle recovery. Thus, practical methods to attenuate EIMD would prove useful to both training and athletic populations. Omega-3 (n-3) supplementation has been shown to mitigate EIMD with evidence of increasing efficacy at higher doses (up to 6 g/day). However, data of its efficacy in trained individuals is limited. Therefore, this study investigated the effects of 6 and 8 g of n-3 supplementation on markers of muscle damage and muscle recovery after eccentric resistance exercise in resistance-trained males. Methods: Using a double-blind, randomized, placebo-controlled design, 26 resistance trained males (23 ± 4 years; 173.6 ± 20.5 cm; 81.9 ± 9.7 kg; 14.2 ± 3.7% body fat) supplemented with 6 (n=10) or 8 g (n=7) of n-3 polyunsaturated fatty acids, or placebo (n=9) for 33 days. On day 30, participants performed a lower body muscle-damaging eccentric resistance exercise bout. Measures of muscle performance, soreness, and damage were taken pre-exercise on day 30 as well as on days 31–33, including vertical jump height (VJH), perceived muscle soreness (PMS), hip and knee range of motion (ROM), repetitions to fatigue (RTF) at 70% 1-RM, and serum creatine kinase (CK) while participants continued to supplement until day 33. Results: There were significant differences in VJH, PMS, and serum CK following the muscle-damaging exercise bout compared to pre-exercise (p0.05) differences between supplementation groups (6 g, 8 g, and placebo) at any time point post-exercise (day 31–33). There were no changes in hip and knee ROM or RTF at any time point or between groups. Vertical jump height and PMS returned to pre-exercise levels despite CK remaining elevated post-exercise. Conclusions: Thirty-three days of 6 and 8 g of n-3 supplementation did not attenuate EIMD or enhance muscle recovery following muscle-damaging eccentric resistance exercise in resistance-trained males. Further research using various n-3 supplementation durations, doses, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations may be needed to establish its efficacy in attenuating EIMD, which may vary between trained and untrained individuals. Furthermore, while circulating CK is commonly used to assess muscle damage, elevated CK levels may not reflect muscle recovery status following muscle-damaging exercise.

Development of sustainable aquaculture practices is a suitable solution to reduce the pressure on overexploited stocks of the Mediterranean sea urchin, Paracentrotus lividus, and to respond to the increasing market demand. To move forward the Blue Growth and following the principles of circular economy, a three-month feeding experiment was conducted to test a sustainable feed based on food processing discards on sea urchins. Two feed formulations differing on the proportions of the two main ingredients (endive outermost leaves and European anchovy discards in a ratio of 60:40 and 80:20 respectively) were prepared and tested on P. lividus gonad yield, development and quality. The results were compared with those of wild sea urchins to assess the differences with natural patterns. Both feed formulations promoted gonad growth resulting in a significantly higher percentage increase in gonad biomass compared with wild specimens (490%, 330% and 78% increase in gonad weight in the feed 60/40, 80/20 and wild sea urchins respectively). Similarly, GSI of reared sea urchins varied by about 3–12% and 14% for sea urchins fed with feeds 80/20 and 60/40 respectively, while that found in wild sea urchins varied by about 3–5%. Gonad development was also boosted by the provision of the sustainable feed, as sexual maturation was faster in reared specimens than in wild ones. At the end of the trial, reared sea urchins showed also a very high (> 90%) frequency of marketable gonad colour. Lastly, the formulation with a more balanced vegetal/animal ratio (feed 60/40) gave the best results overall, combining the highest GSI and the best gonad colouration. Outcomes of this study confirm the suitability of food processing discards as ingredients for sea urchin feeds, although further research is needed to evaluate the effects on nutritional quality and organoleptic features of sea urchin gonads.

Shared information content is represented across brains in idiosyncratic functional topographies. Hyperalignment addresses these idiosyncrasies by using neural responses to project individuals’ brain data into a common model space while maintaining the geometric relationships between distinct patterns of activity or connectivity. The dimensions of this common model capture functional profiles that are shared across individuals such as cortical response profiles collected during a common time-locked stimulus presentation (e.g. movie viewing) or functional connectivity profiles. Hyperalignment can use either response-based or connectivity-based input data to derive transformations that project individuals’ neural data from anatomical space into the common model space. Previously, only response or connectivity profiles were used in the derivation of these transformations. In this study, we developed a new hyperalignment algorithm, hybrid hyperalignment, that derives transformations based on both response-based and connectivity-based information. We used three different movie-viewing fMRI datasets to test the performance of our new algorithm. Hybrid hyperalignment derives a single common model space that aligns response-based information as well as or better than response hyperalignment while simultaneously aligning connectivity-based information better than connectivity hyperalignment. These results suggest that a single common information space can encode both shared cortical response and functional connectivity profiles across individuals.

Background: During the COVID-19 outbreak, healthcare Authorities of Lombardy modified the regional network concerning time-dependent emergencies. Specifically, 13 Macro-Hubs were identified to deliver timely optimal care to patients with acute coronary syndromes (ACS). Aim of this paper is to present the results of this experience. Methods and Results: This is a multicenter, observational study. A total of 953 patients were included, presenting with STEMI in 57.7% of the cases. About 98% of patients received coronary angiography with a median since first medical contact to angiography of 79 (IQR 45–124) minutes for STEMI and 1262 (IQR 643–2481) minutes for NSTEMI.A total of 107 patients (11.2%) had SARS-CoV2 infection, mostly with STEMI (74.8%). The time interval from first medical contact to cath-lab was significant shorter in patients with COVID-19, both in the overall population and in STEMI patients (87 (IQR 41–310) versus 160 (IQR 67–1220) minutes, P = 0.001, and 61 (IQR 23–98) versus 80 (IQR 47–126) minutes, P = 0.01, respectively). In-hospital mortality and cardiogenic shock rates were higher among patients with COVID-19 compared to patients without (32% vs 6%, P

Soil erosion is one of the biggest environmental problems throughout European Union causing considerable soil losses. Vegetation cover provides an important soil protection against runoff and soil erosion. To this aim, unlike annual crops, perennial plants have the advantage of covering soil for a longer time and reducing soil erodibility thanks to SOM increase due to litter effect and to reduction of soil disturbance (no-tillage). Two experiments were carried out in marginal hilly areas (10% slope) of Southern Italy: i) long-term experiment in which it was evaluated the effect of two fertilization doses (N: 100 and 50 kg N ha−1 from urea) on Arundo donax L. biomass production as well as its effect on soil erosion; ii) three-year experiment to evaluate the soil cover capacity of the giant reed by analysing the plant leaf area index (LAI). Results of the two experiments showed a good soil protection of Arundo donax L. that reduced soil losses by 78% as compared to fallow and showed soil erosion reduction not different from permanent meadow thanks to the soil covering during the period with the highest rain erosivity and to the reduction in soil erodibility. The protective effect of Arundo donax L. from rain erosivity was also confirmed by LAI analysis that showed a good soil covering of giant reed in the above mentioned period, even during the initial yield increasing phase following crop transplant. According to biomass yield, from the fifteen year of cultivation in a low fertile inland hilly area of Southern Italy, giant reed was characterized by a yield-decreasing phase that resulted postponed as compared to more fertile environments thus ensuring a longstanding soil protection from soil erosion. In addition, the higher nitrogen fertilization dose (100 kg ha−1 of N) allowed interesting biomass yield as compared to the lower dose (50 kg N ha−1) and kept constant SOC along the year of experimentation due to an improved contribution of leaf fall, root exudates and root turnover to soil. Highlights - Soil erosion is an important environmental problem in Mediterranean hilly areas. - Arundo donax L. can significantly reduce soil erosion in hilly cropland. - Soil protection of giant reed is high during the months with higher rain erosivity. - High N inputs enhance giant reed biomass production and soil fertility conservation. - In hilly areas yields are lower but more stable over time than in more fertile environments.

Subject-specific, functionally defined areas are conventionally estimated with functional localizers and a simple contrast analysis between responses to different stimulus categories. Compared with functional localizers, naturalistic stimuli provide several advantages such as stronger and widespread brain activation, greater engagement, and increased subject compliance. In this study we demonstrate that a subject’s idiosyncratic functional topography can be estimated with high fidelity from that subject’s fMRI data obtained while watching a naturalistic movie using hyperalignment to project other subjects’ localizer data into that subject’s idiosyncratic cortical anatomy. These findings lay the foundation for developing an efficient tool for mapping functional topographies for a wide range of perceptual and cognitive functions in new subjects based only on fMRI data collected while watching an engaging, naturalistic stimulus and other subjects’ localizer data from a normative sample.

Acute pancreatitis is an inflammatory process of the pancreatic gland that may lead to dysregulation of the trans-sulfuration pathway. The aims of this work were firstly to study the methionine cycle as well as the trans-sulfuration pathway using metabolomic and proteomic approaches identifying the causes of this dysregulation in an experimental model of acute pancreatitis; and secondly to reveal the effects of S-adenosylmethionine administration on these pathways. Acute pancreatitis was induced by cerulein in mice, and a group of animals received S-adenosylmethionine treatment. Cerulein-induced acute pancreatitis rapidly caused marked depletion of methionine, S-adenosylmethionine, 5′-methylthioadenosine, cystathionine, cysteine, and glutathione levels in pancreas, but S-adenosylhomocysteine and homocysteine remained unchanged. Protein steady-state levels of S-adenosylhomocysteine-hydrolase and cystathionine gamma-lyase diminished but methylthioadenosine phosphorylase levels increased in pancreas with acute pancreatitis. Although cystathionine β-synthase protein levels did not change with acute pancreatitis, Nos2 mRNA and protein levels were markedly up-regulated and caused tyrosine nitration of cystathionine β-synthase in pancreas. S-adenosylmethionine administration enhanced Nos2 mRNA expression and cystathionine β-synthase nitration and triggered homocysteine accumulation in acute pancreatitis. Furthermore, S-adenosylmethionine administration promoted enrichment of the euchromatin marker H3K4me3 in the promoters of Tnf-α, Il-6, and Nos2 and enhanced the mRNA up-regulation of these genes. Accordingly, S-adenosylmethionine administration increased inflammatory infiltrate and edema in pancreas with acute pancreatitis. In conclusion, tyrosine-nitration of cystathionine β-synthase blockades the trans-sulfuration pathway in acute pancreatitis promoting homocysteine accumulation upon S-adenosylmethionine treatment. Keywords: Acute inflammation, S-adenosylmethionine, Homocysteine, Cystathionine β-synthase, Nitrosative stress

Objective: The clinical picture of children with autism spectrum disorder is characterized by deficits of social interaction and communication, as well as by repetitive interests and activities. Sensory abnormalities are a very frequent feature that often go unnoticed due to the communication difficulties of these patients. This narrative review summarizes the main features of sensory abnormalities and the respective implications for the interpretation of several signs and symptoms of autism spectrum disorder, and therefore for its management. Sources: A search was performed in PubMed (United States National Library of Medicine) about the sensory abnormalities in subjects (particularly children) with autism spectrum disorder. Summary of the findings: Sensory symptoms are common and often disabling in children with autism spectrum disorder, but are not specific for autism, being a feature frequently described also in subjects with intellectual disability. Three main sensory patterns have been described in autism spectrum disorder: hypo-responsiveness, hyper-responsiveness, and sensory seeking; to these, some authors have added a fourth pattern: enhanced perception. Sensory abnormalities may negatively impact the life of these individuals and their families. An impairment not only of unisensory modalities but also of multisensory integration is hypothesized. Conclusions: Atypical sensory reactivity of subjects with autism spectrum disorder may be the key to understand many of their abnormal behaviors, and thus it is a relevant aspect to be taken into account in their daily management in all the contexts in which they live. A formal evaluation of sensory function should be always performed in these children. Resumo: Objetivo: O quadro clínico de crianças com transtorno do espectro do autismo é caracterizado por déficits de interação social e comunicação, bem como por interesses e atividades repetitivos. As alterações sensoriais são uma característica muito frequente que geralmente não é percebida devido às dificuldades de comunicação desses pacientes. Nesta análise narrativa, resumimos as principais características de alterações sensoriais e as respectivas implicações para a interpretação de vários sinais e sintomas do transtorno do espectro do autismo e, portanto, para seu manejo. Fontes: Realizamos uma busca no PubMed (Biblioteca Nacional de Medicina dos Estados Unidos) sobre as alterações sensoriais em indivíduos (principalmente crianças) com transtorno do espectro do autismo. Resumo dos achados: As alterações sensoriais são comuns e geralmente invalidam as crianças com transtorno do espectro do autismo, porém não são específicas do autismo, sendo uma característica frequentemente descrita também em indivíduos com deficiência intelectual. Três principais padrões sensoriais foram descritos no transtorno do espectro do autismo: hiporreatividade, hiperreatividade e busca sensorial; a eles, alguns autores acrescentaram um quarto padrão: percepção aprimorada. As alterações sensoriais podem afetar negativamente a vida desses indivíduos e de suas famílias. Hipotetizamos uma deficiência não apenas das modalidades não sensoriais, mas também da integração multissensorial. Conclusões: A reatividade sensorial atípica de indivíduos com transtorno do espectro do autismo pode ser a chave para entender muitos de seus comportamentos anormais e, portanto, é um aspecto relevante para ser considerado em seu manejo diário em todos os contextos nos quais eles vivem. Sempre se deve fazer uma avaliação formal da função sensorial nessas crianças. Keywords: Autism spectrum disorder, Sensory reactivity, Sensory abnormalities, Sensory seeking, Palavras-chave: Transtorno do espectro autista, Reatividade sensorial, Alterações sensoriais, Busca sensorial

p38α is a redox sensitive MAPK activated by pro-inflammatory cytokines and environmental, genotoxic and endoplasmic reticulum stresses. The aim of this work was to assess whether p38α controls the antioxidant defense in the liver, and if so, to elucidate the mechanism(s) involved and the age-related changes. For this purpose, we used liver-specific p38α-deficient mice at two different ages: young-mice (4 months-old) and old-mice (24 months-old). The liver of young p38α knock-out mice exhibited a decrease in GSH levels and an increase in GSSG/GSH ratio and malondialdehyde levels. However, old mice deficient in p38α had higher hepatic GSH levels and lower GSSG/GSH ratio than young p38α knock-out mice. Liver-specific p38α deficiency triggered a dramatic down-regulation of the mRNAs of the key antioxidant enzymes glutamate cysteine ligase, superoxide dismutase 1, superoxide dismutase 2, and catalase in young mice, which seems mediated by the lack of p65 recruitment to their promoters. Nrf-2 nuclear levels did not change significantly in the liver of young mice upon p38α deficiency, but nuclear levels of phospho-p65 and PGC-1α decreased in these mice. p38α-dependent activation of NF-κB seems to occur through classical IκB Kinase and via ribosomal S6 kinase1 and AKT in young mice. However, unexpectedly the long-term deficiency in p38α triggers a compensatory up-regulation of antioxidant enzymes via NF-κB activation and recruitment of p65 to their promoters. In conclusion, p38α MAPK maintains the expression of antioxidant genes in liver of young animals via NF-κΒ under basal conditions, whereas its long-term deficiency triggers compensatory up-regulation of antioxidant enzymes through NF-κΒ. Keywords: Nuclear factor ƙB, Glutathione, Glutamate cysteine ligase, Superoxide dismutase 1, Superoxide dismutase 2, And catalase

Summary: The human intestinal mucosa is a critical site for absorption, distribution, metabolism, and excretion (ADME)/Tox studies in drug development and is difficult to recapitulate in vitro. Using bioprinting, we generated three-dimensional (3D) intestinal tissue composed of human primary intestinal epithelial cells and myofibroblasts with architecture and function to model the native intestine. The 3D intestinal tissue demonstrates a polarized epithelium with tight junctions and specialized epithelial cell types and expresses functional and inducible CYP450 enzymes. The 3D intestinal tissues develop physiological barrier function, distinguish between high- and low-permeability compounds, and have functional P-gp and BCRP transporters. Biochemical and histological characterization demonstrate that 3D intestinal tissues can generate an injury response to compound-induced toxicity and inflammation. This model is compatible with existing preclinical assays and may be implemented as an additional bridge to clinical trials by enhancing safety and efficacy prediction in drug development. : In Vitro Toxicology Including 3D Culture; Bioengineering; Tissue Engineering Subject Areas: In Vitro Toxicology Including 3D Culture, Bioengineering, Tissue Engineering

Objective: Autism spectrum disorders are lifelong and often devastating conditions that severely affect social functioning and self-sufficiency. The etiopathogenesis is presumably multifactorial, resulting from a very complex interaction between genetic and environmental factors. The dramatic increase in autism spectrum disorder prevalence observed during the last decades has led to placing more emphasis on the role of environmental factors in the etiopathogenesis. The objective of this narrative biomedical review was to summarize and discuss the results of the most recent and relevant studies about the environmental factors hypothetically involved in autism spectrum disorder etiopathogenesis. Sources: A search was performed in PubMed (United States National Library of Medicine) about the environmental factors hypothetically involved in the non-syndromic autism spectrum disorder etiopathogenesis, including: air pollutants, pesticides and other endocrine-disrupting chemicals, electromagnetic pollution, vaccinations, and diet modifications. Summary of the findings: While the association between air pollutants, pesticides and other endocrine-disrupting chemicals, and risk for autism spectrum disorder is receiving increasing confirmation, the hypothesis of a real causal relation between them needs further data. The possible pathogenic mechanisms by which environmental factors can lead to autism spectrum disorder in genetically predisposed individuals were summarized, giving particular emphasis to the increasingly important role of epigenetics. Conclusions: Future research should investigate whether there is a significant difference in the prevalence of autism spectrum disorder among nations with high and low levels of the various types of pollution. A very important goal of the research concerning the interactions between genetic and environmental factors in autism spectrum disorder etiopathogenesis is the identification of vulnerable populations, also in view of proper prevention. Resumo: Objetivo: Os transtornos do espectro autista (TEAs) são vitalícios e normalmente são doenças devastadoras que afetam gravemente o funcionamento social e a autossuficiência. A etiopatogenia é presumivelmente multifatorial, resultante de uma interação muito complexa entre fatores genéticos e ambientais. O aumento drástico na prevalência de TEAs observado nas últimas décadas levou à maior ênfase no papel dos fatores ambientais na etiopatogenia. O objetivo desta análise da narrativa biomédica foi resumir e discutir os resultados dos estudos mais recentes e relevantes sobre os fatores ambientais hipoteticamente envolvidos na etiopatogenia dos TEAs. Fontes: Foi realizada uma pesquisa na Biblioteca Nacional de Medicina dos Estados Unidos (PubMed) sobre os fatores ambientais hipoteticamente envolvidos na etiopatogenia dos TEAs não sindrômicos, incluindo: poluentes atmosféricos, pesticidas e outros desreguladores endócrinos, poluição eletromagnética, vacinas e alterações na dieta. Resumo dos achados: Embora a associação entre poluentes atmosféricos, pesticidas e outros desreguladores endócrinos e o risco de TEA esteja recebendo cada vez mais confirmações, a hipótese de uma relação causal real entre eles ainda precisa de mais dados. Os possíveis mecanismos patogênicos por meio dos quais os fatores ambientais podem causar TEA em indivíduos geneticamente predispostos foram resumidos, com ênfase especial no papel cada vez mais importante da epigenética. Conclusões: Futuras pesquisas devem investigar se há uma diferença significativa na prevalência de TEA entre nações com níveis altos e baixos de vários tipos de poluição. Um objetivo muito importante da pesquisa a respeito das interações entre fatores genéticos e ambientais na etiopatogenia do TEA é a identificação de populações vulneráveis, também em virtude da prevenção adequada. Keywords: Autism spectrum disorder, Neurobiology, Epidemiology, Environmental factors, Air pollutants, Epigenetics, Palavras-chave: Transtorno do espectro autista, Neurobiologia, Epidemiologia, Fatores ambientais, Poluentes atmosféricos, Epigenética

The spectrum of lipid disorders in chronic kidney disease (CKD) is usually characterized by high triglycerides and reduced high dense lipoprotein (HDL), associated with normal or slightly reduced low dense lipoprotein (LDL)-cholesterol. This dyslipidemia is associated with an increased risk for atherosclerotic cardiovascular disease. Keys for the cardiovascular risk reduction in these patients are lowering the number and modifying the composition of the cholesterol-carrying atherogenic lipoprotein particles. Statins have an important role in primary prevention of cardiovascular events and mortality in non-hemodialyzed CKD patients. The benefits in terms of progression of renal failure are contradictory. Patient education regarding dietary regimen should be part of the CKD clinical management.

Background: Q waves and negative T waves are common electrocardiographic (ECG) abnormalities in patients with Hypertrophic Cardiomyopathy (HCM). Several studies correlated ECG findings with presence and extent of fibrosis and hypertrophy; however, their significance remains incompletely clarified. Our study aimed to explain the mechanism behind Q and negative T waves by comparing their positions on a 12-lead ECG with phenotypes observed at Late Gadolinium Enhancement (LGE) Cardiac Magnetic Resonance (CMR). Methods: 12-lead ECG and LGE-CMR were performed in 88 consecutive patients with HCM (42 SD 16 years, 65 males). Using Delta Thickness ratio (DT ratio), and “global” and “parietal” LGE at CMR, the extent and distribution of myocardial hypertrophy and fibrosis were studied in correlation with ECG abnormalities. Results: Q waves in different leads were not associated with “parietal” LGE score. Lateral Q waves correlated with an increased DT ratio Inferior Septum/Lateral wall (p = 0.01). A similar correlation between inferior Q waves and an increased DT Ratio Anterior wall/Inferior wall was of borderline statistical significance (p = 0.06). As expected, ECG signs of LV hypertrophy related to a raised Left Ventricular Mass Index (LVMI) (p

The soil salinity increase in the Mediterranean basin is one of the consequences of the climate change. The aim of this study was to evaluate the adaptability of giant reed (Arundo donax L.) to salinity, in conditions of higher temperatures, in order to hypothesise the future use of giant reed under these conditions. The trial was carried out in pots under a permanent metal structure, open on the sides and with a clear PE on the top. Four levels of soil salinity in the range 3.3-15.5 dS m–1 were imposed. The stem number of the most stressed treatment was about 45% lower than the control and also the stem height was lower than in all other treatments. The green and yellow leaf number decreased as the soil salinity increased, and their sum was significantly lower in the two most stressed treatments. Osmotic potential of the leaf sap was not affected by salinity. Leaf water potential and stomatal conduc- conductance in the saline treatments were lower than in the control. tance Assimilation rate showed similar pattern of stomatal conductance. Intrinsic WUE remained almost stable until July and increased during August under the most stressful conditions. PSII photochemistry was not affected by soil salinity. Biomass yield was not different from the control until to soil ECe 12.0 dS m–1: only the most stressed treatment (15.5 dS m–1) caused yield losses (50%). Tolerance threshold to salinity was 11.2 dS m–1 and the relative yield losses were 11.6% per dS m–1.

Introducción: Los cursos de Ginecología y Obstetricia se dictan en el penúltimo año de la carrera de Doctor en Medicina y representan el primer contacto curricular de los estudiantes con la disciplina. El perfil del egresado del plan de estudios vigente se orienta a la formación de medico generalista, por lo que el egresado debe ser competente en un numero básico de destrezas en el área ginecobstétrica. Objetivos: El objetivo del presente trabajo es introducir el uso de simuladores en la enseñanza del pregrado de ginecología y obstetricia. Metodología: En el transcurso del curso de ginecología del año 2003 los estudiantes fueron divididos en forma aleatorizada en dos grupos, uno de los cuales realizó su entrenamiento con simuladores. Se realizó un seguimiento del aprendizaje por medio de planillas de verificación. Resultados: De los resultados surge que los estudiantes del grupo que realizó su entrenamiento con simuladores tuvieron mas oportunidades de realizar las maniobras sobre todo aquellas que implican mayor dificultad como ser la colocación del especulo y el examen vaginal. Conclusiones: De acuerdo a esto se podría afirmar que la utilización de simuladores constituye una buena herramienta para la adquisición de destrezas en el área gineco obstétrica, y pueden ser una alternativa para la enseñanza a nivel del pregrado.Introduction: The courses in gynaecology and obstetrics are given during the seventh year of the medicine career and represent the students’ first contact with the discipline. Most graduates from our medical school eventually become GPs, so they must be trained in a number of basic skills in obstetrics and gynaecology. Aims: To introduce the use of medical simulators in undergraduate courses of obstetrics and gynaecology. Methodology: During the gynaecology course in the 2003 academic year, students were randomly divided into two groups. The experimental group did their training with medical simulators. Their learning was followed up using a checklist for pelvic examination. Results: The results show that the students that did their training with simulators had more opportunities to perform the manoeuvres, especially those involving greater difficulty like vaginal examination and "speculum" introduction. Conclusions: The use of medical simulators constitutes a good tool for the acquisition of skills in the obgyn area. Simulators provide a useful alternative in undergraduate education.

Introducción: Los cursos de Ginecología y Obstetricia se dictan en el penúltimo año de la carrera de Doctor en Medicina y representan el primer contacto curricular de los estudiantes con la disciplina. El perfil del egresado del plan de estudios vigente se orienta a la formación de medico generalista, por lo que el egresado debe ser competente en un numero básico de destrezas en el área ginecobstétrica. Objetivos: El objetivo del presente trabajo es introducir el uso de simuladores en la enseñanza del pregrado de ginecología y obstetricia. Metodología: En el transcurso del curso de ginecología del año 2003 los estudiantes fueron divididos en forma aleatorizada en dos grupos, uno de los cuales realizó su entrenamiento con simuladores. Se realizó un seguimiento del aprendizaje por medio de planillas de verificación. Resultados: De los resultados surge que los estudiantes del grupo que realizó su entrenamiento con simuladores tuvieron mas oportunidades de realizar las maniobras sobre todo aquellas que implican mayor dificultad como ser la colocación del especulo y el examen vaginal. Conclusiones: De acuerdo a esto se podría afirmar que la utilización de simuladores constituye una buena herramienta para la adquisición de destrezas en el área gineco obstétrica, y pueden ser una alternativa para la enseñanza a nivel del pregrado.

Abstract Objective: Autism spectrum disorders are lifelong and often devastating conditions that severely affect social functioning and self-sufficiency. The etiopathogenesis is presumably multifactorial, resulting from a very complex interaction between genetic and environmental factors. The dramatic increase in autism spectrum disorder prevalence observed during the last decades has led to placing more emphasis on the role of environmental factors in the etiopathogenesis. The objective of this narrative biomedical review was to summarize and discuss the results of the most recent and relevant studies about the environmental factors hypothetically involved in autism spectrum disorder etiopathogenesis. Sources: A search was performed in PubMed (United States National Library of Medicine) about the environmental factors hypothetically involved in the non-syndromic autism spectrum disorder etiopathogenesis, including: air pollutants, pesticides and other endocrine-disrupting chemicals, electromagnetic pollution, vaccinations, and diet modifications. Summary of the findings: While the association between air pollutants, pesticides and other endocrine-disrupting chemicals, and risk for autism spectrum disorder is receiving increasing confirmation, the hypothesis of a real causal relation between them needs further data. The possible pathogenic mechanisms by which environmental factors can lead to autism spectrum disorder in genetically predisposed individuals were summarized, giving particular emphasis to the increasingly important role of epigenetics. Conclusions: Future research should investigate whether there is a significant difference in the prevalence of autism spectrum disorder among nations with high and low levels of the various types of pollution. A very important goal of the research concerning the interactions between genetic and environmental factors in autism spectrum disorder etiopathogenesis is the identification of vulnerable populations, also in view of proper prevention.

After ejaculation, mammalian sperm undergo a series of molecular events conducive to the acquisition of fertilizing competence. These events are collectively known as capacitation and involve acrosomal responsiveness and a vigorous sperm motility called hyperactivation. When mimicked in the laboratory, capacitating bovine sperm medium contains bicarbonate, calcium, albumin and heparin, among other components. In this study, we aimed at establishing a new capacitation protocol for bovine sperm, using calcium ionophore. Similar to our findings using mouse sperm, bovine sperm treated with Ca 2+ ionophore A23187 were quickly immobilized. However, these sperm initiated capacitation after ionophore removal in fresh medium without heparin, and independent of the Protein Kinase A. When A23187-treated sperm were used on in vitro fertilization (IVF) procedures without heparin, eggs showed cleavage rates similar to standardized IVF protocols using heparin containg synthetic oviduct fluid (IVF-SOF). However, when A23187 pre-treated sperm were further used for inseminating eggs in complete IVF-SOF-heparin, a significantly higher percentage of embryo development was observed, suggesting a synergism between two different signaling pathways during bovine sperm capacitation. These results have the potential to improve current protocols for bovine IVF that could also be applied in other species of commercial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures There are no relationships relevant to the contents of this paper to disclose.

To succeed in fertilization, spermatozoa must decode environmental cues which require a set of ion channels. Recent findings have revealed that K(+) and Cl(-) channels participate in some of the main sperm functions. This work reviews the evidence indicating the involvement of K(+) and Cl(-) channels in motility, maturation, and the acrosome reaction, and the advancement in identifying their molecular identity and modes of regulation. Improving our insight on how these channels operate will strengthen our ability to surmount some infertility problems, improve animal breeding, preserve biodiversity, and develop selective and secure male contraceptives., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Exocytosis of the acrosome (the acrosome reaction) is a terminal morphological alteration that sperm must undergo prior to penetration of the extracellular coat of the egg. Ca(2+) is an essential mediator of this regulated secretory event. Aided by a streptolysin-O permeabilization protocol developed in our laboratory, we have previously demonstrated requirements for Rab3A, NSF, and synaptotagmin VI in the human sperm acrosome reaction. Interestingly, Rab3A elicits an exocytotic response of comparable magnitude to that of Ca(2+). Here, we report a direct role for the SNARE complex in the acrosome reaction. First, the presence of SNARE proteins is demonstrated by Western blot. Second, the Ca(2+)-triggered acrosome reaction is inhibited by botulinum neurotoxins BoNT/A, -E, -C, and -F. Third, antibody inhibition studies show a requirement for SNAP-25, SNAP-23, syntaxins 1A, 1B, 4, and 6, and VAMP 2. Fourth, addition of bacterially expressed SNAP-25 and SNAP-23 abolishes exocytosis. Acrosome reaction elicited by Rab3-GTP is also inhibited by BoNT/A, -C, and -F. Taken together, these results demonstrate a requirement for members of all SNARE protein families in the Ca(2+)- and Rab3A-triggered acrosome reaction. Furthermore, they indicate that the onset of sperm exocytosis relies on the functional assembly of SNARE complexes., ((C)2002 Elsevier Science (USA).)

We previously demonstrated that mouse sperm capacitation is accompanied by a time-dependent increase in protein tyrosine phosphorylation that is dependent on the presence of BSA, Ca2+, and NaHCO(3), all three of which are also required for this maturational event. We also demonstrated that activation of protein kinase A (PK-A) is upstream of this capacitation-associated increase in protein tyrosine phosphorylation. BSA is hypothesized to modulate capacitation through the removal of cholesterol from the sperm plasma membrane. In this report, we demonstrate that incubation of mouse sperm medium containing BSA results in a release of cholesterol from the sperm plasma membrane to the medium; release of this sterol does not occur in medium devoid of BSA. We next determined whether cholesterol release leads to changes in protein tyrosine phosphorylation. Blocking the action of BSA by adding exogenous cholesterol-SO-(4) to the BSA-containing medium inhibits the increase in protein tyrosine phosphorylation as well as capacitation. This inhibitory effect is overcome by (1) the addition of increasing concentrations of BSA at a given concentration of cholesterol-SO-(4) and (2) the addition of dibutyryl cAMP plus IBMX. High-density lipoprotein (HDL), another cholesterol binding protein, also supports the capacitation-associated increase in protein tyrosine phosphorylation through a cAMP-dependent pathway, whereas proteins that do not interact with cholesterol have no effect. HDL also supports sperm capacitation, as assessed by fertilization in vitro. Finally, we previously demonstrated that HCO-(3) is necessary for the capacitation-associated increase in protein tyrosine phosphorylation and demonstrate here, by examining the effectiveness of HCO-(3) or BSA addition to sperm on protein tyrosine phosphorylation, that the HCO-(3) effect is downstream of the site of BSA action. Taken together, these data demonstrate that cholesterol release is associated with the activation of a transmembrane signal transduction pathway involving PK-A and protein tyrosine phosphorylation, leading to functional maturation of the sperm., (Copyright 1999 Academic Press.)