Is exposure to pesticides associated with biological aging? A systematic review and meta-analysis.

OBJECTIVE: Exposure to pesticides is a risk factor for various diseases, yet its association with biological aging remains unclear. We aimed to systematically investigate the relationship between pesticide exposure and biological aging. METHODS: PubMed, Embase and Web of Science were searched from inception to August 2023. Observational studies investigating the association between pesticide exposure and biomarkers of biological aging were included. Three-level random-effect meta-analysis was used to synthesize the data. Risk of bias was assessed by the Newcastle-Ottawa Scale. RESULTS: Twenty studies evaluating the associations between pesticide exposure and biomarkers of biological aging in 10,368 individuals were included. Sixteen reported telomere length and four reported epigenetic clocks. Meta-analysis showed no statistically significant associations between pesticide exposure and the Hannum clock (pooled ß = 0.27; 95%CI: -0.25, 0.79), or telomere length (pooled Hedges'g = -0.46; 95%CI: -1.10, 0.19). However, the opposite direction of effect for the two outcomes showed an indication of possible accelerated biological aging. After removal of influential effect sizes or low-quality studies, shorter telomere length was found in higher-exposed populations. CONCLUSION: The existing evidence for associations between pesticide exposure and biological aging is limited due to the scarcity of studies on epigenetic clocks and the substantial heterogeneity across studies examining telomere length. High-quality studies incorporating more biomarkers of biological aging, focusing more on active chemical ingredients of pesticides and accounting for potential confounders are needed to enhance our understanding of the impact of pesticides on biological aging.

Milk Bioactive Compounds and Gut Microbiota Modulation: The Role of Whey Proteins and Milk Oligosaccharides.

A strong correlation between the occurrence of various pathological conditions and intestinal dysbiosis is supported by a range of strong evidence. Vice versa, many pathologies have been shown, in turn, to be responsible for alterations in the gut microbiota, a condition that can worsen illness outcomes and response to therapies. For these reasons, great efforts have been made, and studies are still ongoing, to elucidate the mechanisms underlying gut microbiota alterations and to search for pharmacologic or other strategies that can effectively restore the gut microbiota. In this narrative review, we examined the most significant literature on the role of some milk bioactive compounds, such as milk oligosaccharides and whey proteins, in modulating the composition of the gut microbiota and the underlying mechanisms of action, with the aim of investigating the impact of the microbiota changes mediated by these milk bioactive molecules on human health, and their potential use as therapeutics to treat or adjuvate the treatment of gut dysbiosis and associated pathologies.

A Delphi consensus to identify the key screening tests/questions for a digital neurological examination for epidemiological research.

BACKGROUND: Most neurological diseases have no curative treatment; therefore, focusing on prevention is key. Continuous research to uncover the protective and risk factors associated with different neurological diseases is crucial to successfully inform prevention strategies. eHealth has been showing promising advantages in healthcare and public health and may therefore be relevant to facilitate epidemiological studies. OBJECTIVE: In this study, we performed a Delphi consensus exercise to identify the key screening tests to inform the development of a digital neurological examination tool for epidemiological research. METHODS: Twelve panellists (six experts in neurological examination, five experts in data collection-two were also experts in the neurological examination, and three experts in participant experience) of different nationalities joined the Delphi exercise. Experts in the neurological examination provided a selection of items that allow ruling out neurological impairment and can be performed by trained health workers. The items were then rated by them and other experts in terms of their feasibility and acceptability. RESULTS: Ten tests and seven anamnestic questions were included in the final set of screening items for the digital neurological examination. Three tests and five anamnestic questions were excluded from the final selection due to their low ratings on feasibility. CONCLUSION: This work identifies the key feasible and acceptable screening tests and anamnestic questions to build an electronic tool for performing the neurological examination, in the absence of a neurologist.

eHealth tools to assess the neurological function for research, in absence of the neurologist - a systematic review, part I (software).

BACKGROUND: Neurological disorders remain a worldwide concern due to their increasing prevalence and mortality, combined with the lack of available treatment, in most cases. Exploring protective and risk factors associated with the development of neurological disorders will allow for improving prevention strategies. However, ascertaining neurological outcomes in population-based studies can be both complex and costly. The application of eHealth tools in research may contribute to lowering the costs and increase accessibility. The aim of this systematic review is to map existing eHealth tools assessing neurological signs and/or symptoms for epidemiological research. METHODS: Four search engines (PubMed, Web of Science, Scopus & EBSCOHost) were used to retrieve articles on the development, validation, or implementation of eHealth tools to assess neurological signs and/or symptoms. The clinical and technical properties of the software tools were summarised. Due to high numbers, only software tools are presented here. FINDINGS: A total of 42 tools were retrieved. These captured signs and/or symptoms belonging to four neurological domains: cognitive function, motor function, cranial nerves, and gait and coordination. An additional fifth category of composite tools was added. Most of the tools were available in English and were developed for smartphone device, with the remaining tools being available as web-based platforms. Less than half of the captured tools were fully validated, and only approximately half were still active at the time of data collection. INTERPRETATION: The identified tools often presented limitations either due to language barriers or lack of proper validation. Maintenance and durability of most tools were low. The present mapping exercise offers a detailed guide for epidemiologists to identify the most appropriate eHealth tool for their research. FUNDING: The current study was funded by a PhD position at the University of Groningen. No additional funding was acquired.

Exposure assessment for repeated sub-concussive head impacts in soccer: The HEalth and Ageing Data IN the Game of football (HEADING) study.

The purpose of this paper was to develop exposure estimates for repetitive sub-concussive head impacts (RSHI) for use in epidemiological analyses. We used a questionnaire to collect lifetime history of heading and other head contacts associated with training and playing football from 159 former footballers all members of the English professional football association. We used linear mixed effect regression with player as the random effect, to model the number of headers, blows to the head and head-to-head impacts as a function of potential exposure affecting factors, which were treated as the fixed effects. Exposure affecting factors included playing position, league, context of play (game vs training) and decade of play. Age at time of response to the questionnaire was also included in the models. In model results, playing position was important, with RSHIs being highest among defenders and lowest among goalkeepers. Players headed the ball more during games than in training, and when playing in amateur or youth leagues compared with semi-professional or professional leagues. The average number of reported head impacts declined linearly throughout the observation period (1949-2015). The derived final model for headers explained 43%, 9% and 36% of the between player, within player and total variance in exposure, respectively with good precision and predictive performance. These findings are generally in agreement with previously published results pointing towards the models forming a valid method for estimating exposure to RSHI among former footballers although some further external validation is still warranted.

Implication of Sodium Hypochlorite as a Sanitizer in Ready-to-Eat Salad Processing and Advantages of the Use of Alternative Rapid Bacterial Detection Methods.

The use of disinfection agents in the washing processing of ready-to-eat (RTE) vegetables, especially sodium hypochlorite, is a common industrial practice performed to enhance microbiological quality. However, some studies have reported a restart of bacterial growth and a substantial increase in bacterial load during early storage associated with the use of disinfection agents, which might represent a risk for consumers. We evaluated the effect of sodium hypochlorite on bacterial growth trends during the shelf-life in Lactuca sativa, simulating the industrial procedures for RTE vegetable packaging. Immediately after sodium hypochlorite treatment, an effective abatement of the bacterial load was observed, followed by a restart of growth throughout storage. After 5 days, the bacterial load was close to that reached by the control samples, indicating that the net increase in bacterial load was significantly higher in the treated samples. This might be ascribed to the reduction in competitive microflora and/or to the induction of adaptive responses by resting bacteria, which might select disinfectant-resistant bacteria. These findings elicit some concerns about the actual duration of the shelf-life; products might decrease their microbiological quality earlier during storage, pointing out the need to better clarify the impact of sodium hypochlorite as a sanitizer to closer consider its use in RTE vegetable processing. Furthermore, due to the importance of the rapid estimation of bacterial load and the early detection of foodborne pathogens throughout the food chain, the accuracy of the rapid bacteria detection method, the Micro Biological Survey (MBS), and its effectiveness for microbiological analyses of RTE vegetables were evaluated.

Cadmium Sulfide Quantum Dots, Mitochondrial Function and Environmental Stress: A Mechanistic Reconstruction through In Vivo Cellular Approaches in Saccharomyces cerevisiae.

Research on the effects of engineered nanomaterials (ENMs) on mitochondria, which represent one of the main actors in cell function, highlighted effects on ROS production, gametogenesis and organellar genome replication. Specifically, the mitochondrial effects of cadmium sulfide quantum dots (CdS QDs) exposure can be observed through the variation in enzymatic kinetics at the level of the respiratory chain and also by analyzing modifications of reagent and products in term of the bonds created and disrupted during the reactions through Fourier-transform infrared spectroscopy (FTIR). This study investigated both in intact cells and in isolated mitochondria to observe the response to CdS QDs treatment at the level of electron transport chain in the wild-type yeast Saccharomyces cerevisiae and in the deletion mutant Δtom5, whose function is implicated in nucleo-mitochondrial protein trafficking. The changes observed in wild type and Δtom5 strains in terms of an increase or decrease in enzymatic activity (ranging between 1 and 2 folds) also differed according to the genetic background of the strains and the respiratory chain functionality during the CdS QDs treatment performed. Results were confirmed by FTIR, where a clear difference between the QD effects in the wild type and in the mutant strain, Δtom5, was observed. The utilization of these genetic and biochemical approaches is instrumental to clarify the mitochondrial mechanisms implicated in response to these types of ENMs and to the stress response that follows the exposure.

A new point-of-care test for the rapid antimicrobial susceptibility assessment of uropathogens.

Bacterial resistance to antimicrobials is considered a major issue worldwide. This condition may account for treatment failure of urinary tract infections, which are among the most common infections both in community and healthcare settings. Therapy against uropathogens is generally administered empirically, possibly leading to unsuccessful therapy, recurrence and development of antibiotic resistance. The reduction in analytical time to obtain antimicrobial susceptibility test (AST) results could play a key role in reducing the cost of healthcare, providing information about antibiotic efficacy and thus preventing from either exploiting new and expensive antibiotics unnecessarily or using obsolete and ineffective ones. A more rational choice among treatment options would hence lead to more effective treatment and faster resolution. In this paper we evaluated the performance of a new Point Of Care Test (POCT) for the rapid prediction of antimicrobial susceptibility in urine samples performed without the need of a laboratory or specialized technicians. 349 patients were enrolled in two open-label, monocentric, non-interventional clinical trials in partnership with an Emergency Medicine ward and the Day Hospital of two large healthcare facilities in Rome. Antibiogram was carried out on 97 patients. Results from analysis of urine samples with the POCT were compared with those from routine AST performed on culture-positive samples, displaying high accuracy (>90%) for all tested antimicrobial drugs and yielding reliable results in less than 12 hours from urine collection thus reducing analytical and management costs.

LC-HRMS analysis of 13 classes of pharmaceutical substances in food supplements.

Food supplements should not contain substances considered unsafe or pose a health risk to consumers. In recent years illegal adulterants have been found in various functional foods without notification of their presence or amount in the labelling. In this study, a validated method was developed and applied as a screening method to detect 124 forbidden substances belonging to 13 classes of compounds in food supplements. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) and a simple and rapid extraction protocol was applied to 110 food supplements collected from the internet market or during official controls in Italy. The percentage of non-compliant samples was 4.5%, relatively high compared with the official control results for these substances usually obtained on other food matrices. The results suggested the need to strengthen controls in this field to detect food supplement adulteration, which represents a potential health risk for the consumer.

A narrative review of alternative transmission routes of COVID 19: what we know so far.

The Coronavirus disease 19 (COVID-19) pandemics, caused by severe acute respiratory syndrome coronaviruses, SARS-CoV-2, represent an unprecedented public health challenge. Beside person-to-person contagion via airborne droplets and aerosol, which is the main SARS-CoV-2's route of transmission, alternative modes, including transmission via fomites, food and food packaging, have been investigated for their potential impact on SARS-CoV-2 diffusion. In this context, several studies have demonstrated the persistence of SARS-CoV-2 RNA and, in some cases, of infectious particles on exposed fomites, food and water samples, confirming their possible role as sources of contamination and transmission. Indeed, fomite-to-human transmission has been demonstrated in a few cases where person-to-person transmission had been excluded. In addition, recent studies supported the possibility of acquiring COVID-19 through the fecal-oro route; the occurrence of COVID-19 gastrointestinal infections, in the absence of respiratory symptoms, also opens the intriguing possibility that these cases could be directly related to the ingestion of contaminated food and water. Overall, most of the studies considered these alternative routes of transmission of low epidemiological relevance; however, it should be considered that they could play an important role, or even be prevalent, in settings characterized by different environmental and socio-economic conditions. In this review, we discuss the most recent findings regarding SARS-CoV-2 alternative transmission routes, with the aim to disclose what is known about their impact on COVID-19 spread and to stimulate research in this field, which could potentially have a great impact, especially in low-resource contexts.

Compound climate-pollution extremes in Santiago de Chile.

Cities in the global south face dire climate impacts. It is in socioeconomically marginalized urban communities of the global south that the effects of climate change are felt most deeply. Santiago de Chile, a major mid-latitude Andean city of 7.7 million inhabitants, is already undergoing the so-called "climate penalty" as rising temperatures worsen the effects of endemic ground-level ozone pollution. As many cities in the global south, Santiago is highly segregated along socioeconomic lines, which offers an opportunity for studying the effects of concurrent heatwaves and ozone episodes on distinct zones of affluence and deprivation. Here, we combine existing datasets of social indicators and climate-sensitive health risks with weather and air quality observations to study the response to compound heat-ozone extremes of different socioeconomic strata. Attributable to spatial variations in the ground-level ozone burden (heavier for wealthy communities), we found that the mortality response to extreme heat (and the associated further ozone pollution) is stronger in affluent dwellers, regardless of comorbidities and lack of access to health care affecting disadvantaged population. These unexpected findings underline the need of a site-specific hazard assessment and a community-based risk management.

Mind the gap: Data availability, accessibility, transparency, and credibility during the COVID-19 pandemic, an international comparative appraisal.

Data transparency has played a key role in this pandemic. The aim of this paper is to map COVID-19 data availability and accessibility, and to rate their transparency and credibility in selected countries, by the source of information. This is used to identify knowledge gaps, and to analyse policy implications. The availability of a number of COVID-19 metrics (incidence, mortality, number of people tested, test positive rate, number of patients hospitalised, number of patients discharged, the proportion of population who received at least one vaccine, the proportion of population fully vaccinated) was ascertained from selected countries for the full population, and for few of stratification variables (age, sex, ethnicity, socio-economic status) and subgroups (residents in nursing homes, inmates, students, healthcare and social workers, and residents in refugee camps). Nine countries were included: Bangladesh, Indonesia, Iran, Nigeria, Turkey, Panama, Greece, the UK, and the Netherlands. All countries reported periodically most of COVID-19 metrics on the total population. Data were more frequently broken down by age, sex, and region than by ethnic group or socio-economic status. Data on COVID-19 is partially available for special groups. This exercise highlighted the importance of a transparent and detailed reporting of COVID-19 related variables. The more data is publicly available the more transparency, accountability, and democratisation of the research process is enabled, allowing a sound evidence-based analysis of the consequences of health policies.

Increased Gal-3BP plasma levels in hospitalized patients infected with SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has quickly turned into a health, financial and societal problem globally. The complex pathogenesis of severe acute respiratory syndrome coronavirus centers on the unpredictable clinical progression of the disease, which may evolve abruptly and results in critical and life-threatening clinical complications. Effective laboratory biomarkers that can classify patients according to risk of progression to severe disease are essential for ensuring timely treatment. Gal-3BP is a human secreted protein with innate immune functions, which is upregulated in viral infections, promotes inflammation and has been shown to induce IL-6 expression. In this study, Gal-3BP plasma levels were measured retrospectively in a cohort of 84 hospitalized COVID-19 patients. These were classified as having either "non-severe" or "severe" disease. Compared to healthy controls, Gal-3BP plasma levels were markedly increased in COVID-19 patients (P < 0.0001). Moreover, the levels were higher in severe than in non-severe patients (P < 0.05). As expected, patients with severe disease had plasma levels of IL-6 higher than patients with non-severe disease (P < 0.01). In non-severe disease patients, Gal-3BP levels collected at a late stage (13.3 + 5.7 days after the first positive PCR result) were significantly lower than those collected at an early stage (4.2 + 2.9 days form the first positive PCR result). Larger prospective analyses are needed to strength our understanding of the prognostic utility of Gal-3BP in COVID-19 patients.

Working toward a transdisciplinary approach to teaching and learning planetary health-A collective reflection.

Background: In order to educate the next generation of leaders to work at reverting the damaging effects of the Anthropocene, there is an increasing need to incorporate more environmental-related aspects in all teaching programmes, including the health-related. Planetary health is a complex field which can benefit from a transdisciplinary pedagogical approach. The aim of this research was to evaluate an approach working toward transdisciplinarity applied to a course of Planetary Health taught at the Bachelor degree Global Responsibility & Leadership of the University of Groningen through substantive feedback and reflections from the students. Methods: By the end of the course, a focus group was conducted with the students inviting them to reflect on the different aspects of the pedagogical approach, evaluating their effectiveness. A thematic analysis was conducted on the transcribed focus group. Results: The students appreciated the added value of working toward a transdisciplinary approach and peer-to-peer learning and teaching adopted in the Planetary Health course, as a way of enhancing their learning experience. They pointed out the need of incorporating a transcultural approach into the transdisciplinary one, as a way not only to improve their learning experience, but also to enrich the transdisciplinarity itself. Conclusion: Incorporating a process toward transdisciplinary and transcultural teaching of planetary health into undergraduate programmes was found to be of added value. The peer-to-peer horizontal learning opportunities were seen as a way for taking advantage of the collaborative, informal teaching and community building serving the overall scope of the course.

Protein Analysis of A. halleri and N. caerulescens Hyperaccumulators When Exposed to Nano and Ionic Forms of Cd and Zn.

Hyperaccumulator plant species growing on metal-rich soils can accumulate high quantity of metals and metalloids in aerial tissues, and several proteomic studies on the molecular mechanisms at the basis of metals resistance and hyperaccumulation have been published. Hyperaccumulator are also at the basis of the phytoremediation strategy to remove metals more efficiently from polluted soils or water. Arabidopsis halleri and Noccea caerulescens are both hyperaccumulators of metals and nano-metals. In this study, the change in some proteins in A. halleri and N. caerulescens was assessed after the growth in soil with cadmium and zinc, provided as sulphate salts (CdSO4 and ZnSO4) or sulfide quantum dots (CdS QDs and ZnS QDs). The protein extracts obtained from plants after 30 days of growth were analyzed by 2D-gel electrophoresis (2D SDS-PAGE) and identified by MALDI-TOF/TOF mass spectrometry. A bioinformatics analysis was carried out on quantitative protein differences between control and treated plants. In total, 43 proteins resulted in being significatively modulated in A. halleri, while 61 resulted in being modulated in N. caerulescens. Although these two plants are hyperaccumulator of both metals and nano-metals, at protein levels the mechanisms involved do not proceed in the same way, but at the end bring a similar physiological result.

Coumarin-Induced Hepatotoxicity: A Narrative Review.

Coumarin is an effective treatment for primary lymphoedema, as well as lymphoedema related to breast cancer radiotherapy or surgery. However, its clinical use is limited in several countries due to the possible occurrence of hepatotoxicity, mainly in the form of mild to moderate transaminase elevation. It is worth noting that only a few cases of severe hepatotoxicity have been described in the literature, with no reported cases of liver failure. Data available on coumarin absorption, distribution, metabolism, and excretion have been reviewed, focusing on hepatotoxicity studies carried out in vitro and in vivo. Finally, safety and tolerability data from clinical trials have been thoroughly discussed. Based on these data, coumarin-induced hepatotoxicity is restricted to a small subset of patients, probably due to the activation in these individuals of alternative metabolic pathways involving specific CYP450s isoforms. The aim of this work is to stimulate research to clearly identify patients at risk of developing hepatotoxicity following coumarin treatment. Early identification of this subset of patients could open the possibility of more safely exploiting the therapeutical properties of coumarin, allowing patients suffering from lymphoedema to benefit from the anti-oedematous activity of the treatment.

Combination of Biochemical, Molecular, and Synchrotron-Radiation-Based Techniques to Study the Effects of Silicon in Tomato (Solanum Lycopersicum L.).

The work focused on the analysis of two cultivars of tomato (Solanum lycopersicum L.), Aragon and Gladis, under two different treatments of silicon, Low, 2 L of 0.1 mM CaSiO3, and High, 0.5 mM CaSiO3, weekly, for 8 weeks, under stress-free conditions. We subsequently analyzed the morphology, chemical composition, and elemental distribution using synchrotron-based µ-XRF techniques, physiological, and molecular aspects of the response of the two cultivars. The scope of the study was to highlight any significant response of the plants to the Si treatments, in comparison with any response to Si of plants under stress. The results demonstrated that the response was mainly cultivar-dependent, also at the level of mitochondrial-dependent oxidative stress, and that it did not differ from the two conditions of treatments. With Si deposited mainly in the cell walls of the cells of fruits, leaves, and roots, the treatments did not elicit many significant changes from the point of view of the total elemental content, the physiological parameters that measured the oxidative stress, and the transcriptomic analyses focalized on genes related to the response to Si. We observed a priming effect of the treatment on the most responsive cultivar, Aragon, in respect to future stress, while in Gladis the Si treatment did not significantly change the measured parameters.

Galectin-3 binding protein stimulated IL-6 expression is impeded by antibody intervention in SARS-CoV-2 susceptible cell lines.

COVID-19 is the global pandemic that affected our population in the past 2 years. Considerable research has been done to better understand the pathophysiology of this disease and to identify new therapeutic targets, especially for severe cases. Galectin-3 (Gal-3) is a receptor present at the surface of different cell types, namely epithelial and inflammatory cells, which has been described as a severity marker in COVID-19. The activation of Gal-3 through its binding protein (Gal-3BP) is directly linked to the production of pro-inflammatory cytokines that contribute for the cytokine storm (CS) observed in severe COVID-19 patients. Here, we show that D2, a recombinant fragment of the lectin-binding region of Gal-3BP was able to stimulate the expression of IL-6 in colon and lung epithelial cell lines in ß-galactoside dependent manner. We further show that D2-induced IL-6 augmentation was reduced by the anti-Gal-3BP monoclonal antibody 1959. Our data confirm and extend prior findings of Gal-3BP mediated IL-6 induction, enlightening the potential of its antibody-mediated s blockage for the prevention and treatment of CS and severe disease in COVID-19 patients.