Chronic Effects Research Articles

Associations between neonicotinoids and liver function measures in US adults: National Health and Nutrition Examination Survey 2015–2016

Background: Toxicological studies indicate that neonicotinoids may be associated with disruptions in liver function due to an increase in oxidative stress. There are scant epidemiological studies investigating the chronic hepatotoxic effects of neonicotinoids. Objective: To examine the association between detectable concentrations of parent neonicotinoids and neonicotinoid metabolites with liver function markers among US adults, and whether sex modifies this association. Methods: National Health and Nutrition Examination Survey 2015–2016 data were used to estimate associations between detectable neonicotinoids and serum alkaline phosphatase (ALP), alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transaminase (GGT), albumin, total bilirubin, total protein, and Hepatic Steatosis Index (HSI) using multiple linear regression. Results: Detectable levels of N-desmethyl-acetamiprid were associated with a decrease in GGT (β = −3.54 unit/l; 95% confidence interval [CI] = −6.48, −0.61) and detectable levels of 5-hydroxy-imidacloprid were associated with a decrease in HSI (β = −1.11; 95% CI = −2.14, −0.07). Sex modified the association between any parent neonicotinoid and ALP (P int = 0.064) and the association between clothianidin and ALP (P int = 0.019), with a pattern of positive associations in males and inverse associations in females, though stratified associations did not reach statistical significance. Sex also modified the association between 5-hydroxy-imidacloprid and total protein (P int = 0.062), with a significant positive association in females (β = 0.14 g/dl; 95% CI = 0.03, 0.25) and a null association in males. Conclusion: Detectable concentrations of neonicotinoid metabolites were inversely associated with GGT and HSI in US adults. Evidence suggests neonicotinoids may influence liver function differently depending on sex. Future research is recommended to replicate the findings as the study was limited in its cross-sectional nature and inability to examine continuous neonicotinoid concentrations with liver function.

Evolving Standards of Care in the Management of Localized Colorectal Cancer.

The treatment of patients with localized rectal cancer is complex and requires input from a multidisciplinary team. Baseline local staging and mismatch repair protein testing are vital to develop individualized treatment plans. There are multiple options in terms of treatment modalities and sequencing, including transanal excision, short-course radiation, long-course chemoradiation, chemotherapy doublet or triplet, nonoperative management, and immune checkpoint blockade for patients with mismatch repair deficient tumors. While localized colon cancer is typically treated with surgical resection and consideration of adjuvant chemotherapy, emerging data suggest that neoadjuvant chemotherapy may be beneficial in patients with higher-risk disease. Quality-of-life considerations are imperative to prevent potential chronic effects on psychosocial health, neuropathy, fertility, and bowel, bladder, and sexual function. The omission of radiation or surgery can mitigate these toxicities without diminishing oncologic outcomes. The optimal treatment plan and sequence is not a one-size-fits-all approach but rather should be personalized to the patient's disease burden, tumor location, comorbidities, and preferences.

Side effects of dermato-oncologic therapies

Immune checkpoint inhibitors (ICIs) such as PD(L)1 and CTLA4 antibodies as well as targeted therapies such as BRAF and MEK inhibitors have significantly improved the systemic treatment of skin cancer in adjuvant and advanced therapy settings. All these drugs differ in their spectrum of side effects. The aim of this article is to provide an overview of the spectrum of side effects of dermato-oncological therapies and their management, taking into account the current literature. The most important side effects of ICIs, the CCR4 inhibitor mogamulizumab, the ImmTAC tebentafusp, the BRAF and MEK inhibitors and the multityrosine kinase inhibitor imatinib are considered. Side effects can manifest themselves in all organ systems. Chronic side effects and long-term harm are possible, especially with ICIs, and require close therapy monitoring and patient education. Knowledge of the side effects and the temporal, sometimes delayed course of their occurrence are essential for diagnosis and prompt initiation of therapy.

Acute procedural characteristics and safety of pulsed field cryoablation for persistent AF: multicenter results from the first in human PARALELL trial

Abstract Introduction Pulsed Field Cryoablation (PFCA) is dual-energy cardiac ablation modality consisting of short-duration ultra-low temperature cryoablation (ULTC) followed immediately by pulsed electric field ablation (PFA) delivered from the same catheter. It has been hypothesized that it may be beneficial to combine the efficiency of PFA with the contact and stability offered by ULTC. In patients with persistent atrial fibrillation, PFCA could be of particular benefit when creating extended lesion sets beyond pulmonary vein isolation such as posterior wall ablation. By focusing the electric field in high-impedance frozen tissue, PFCA may increase lesion depth and durability despite lower delivered current, while minimizing PFA-related microbubbles and skeletal muscle contraction. Purpose To report the acute outcomes of PFCA observed in the first-in-human PARALELL trial. Methods PFCA was performed using a novel stylet-driven catheter connected to the dedicated ULTC and PFA energy sources. The protocol-defined lesion set included pulmonary vein isolation and posterior wall (PW) ablation, with additional left and right atrial targets per operator discretion. Circular and linear lesions of varying dimensions were created by in-vivo shaping of the flexible, 11 cm-long ablation element of the catheter using exchangeable stylets. The ULTC freeze of 30 second duration was followed immediately by bipolar, biphasic PFA pulse trains delivered sequentially between the pairs of sixteen 3-mm electrodes evenly spaced along the ablation element. Results At 5 European and Canadian sites, 26 patients (age 68±9 years, 88.5% male, median left atrial size 45 mm, IQR [43 mm-48 mm]) underwent PFCA with 22.6 ± 9.6 ablation lesions per patient. The lesion set included 11.9 ± 4.1 lesions to PVs, 7.4 ± 2.7 to the PW, and in 14 patients, 6.6 ± 9.0 lesions to other atrial targets (left atrial roof and floor, PV carinas, mitral and cavotricuspid isthmuses). Isolation was achieved in 94.2% (98 of 104) of PVs and 92.3% (24 of 26) of PWs. The average procedure time was 130.3 ± 40.9 minutes, with catheter dwell time of 78.8 ± 26.0 minutes. Procedure-related groin hematoma at discharge was the only serious adverse event by site adjudication. Intracardiac echocardiography (ICE) performed in 18 patients identified Grade I (FEW) microbubbles in 1.3% (5 of 398) of ablations. Similarly, only faint muscular contractions were observed in 2 of 26 patients, occurring during 1.2% (4 of 339) of lesions placed in 15 patients not receiving any paralytic agents. Conclusions This initial multi-center experience suggests that PFCA can be efficiently performed on multiple atrial targets using a single versatile catheter system, with high acute success and good early safety profile, including minimal occurrence of PFA-related microbubbles and skeletal muscle contractions. The evaluation of the chronic 12-month effectiveness vs ULTC benchmarks and PFA comparators is ongoing.

Chronic exercise effects on overall depression severity and distinct depressive symptoms in older adults: A protocol of a systematic and meta-analytic review.

There is high evidence that chronic exercise benefits overall depression severity in older adults. However, late-life depression is characterized by considerable heterogeneity in clinical manifestation emphasizing the need for more individualized exercise intervention programs. Therefore, the objective of the proposed review is to investigate the effects of chronic exercise on overall depression severity and on different symptoms of depression in randomized controlled trials (RCTs) including older adults with a mean age of at least 60 years, and by considering the moderating effects of intervention characteristics and individual characteristics. This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). We will use the Population-Intervention-Comparator-Outcomes-Study design (PICOS) criteria for study inclusion and will search the following database sources for relevant RCTs: Web of Science, Academic Search Complete, CINAHL, APA Psycinfo, SPORTDiscuss, Cochrane. Two independent reviewers will conduct the study selection, data extraction, and quality assessment. Disagreement will be solved by a third reviewer. Primary outcome will be changes in overall depression severity and secondary outcomes will encompass changes in symptoms of depression as defined by the DSM-5, such as sleep quality, fatigue, anxiety, mood, apathy, changes in weight, information processing speed, and executive functions, from baseline until the end of the intervention and to any available intermediary measurement or follow up. Meta-analysis will be undertaken to synthesize the effects of chronic exercise on primary and secondary outcomes. Subgroup analysis will investigate the moderating effects of intervention characteristics (frequency, intensity, duration, type of exercise, cognitive demand, social interactions, exercise supervision, behavioral change techniques, compliance, study design, dropout-rate, type of control group) and individual characteristics (age, sex, education, functional capacity, global cognition, population) on primary and secondary outcomes. Additionally, we plan to assess quality of evidence and publication bias, and to carry out sensitivity analysis. The results of the proposed review are anticipated to have a substantial impact on research and clinical practice. On the one hand, the review's conclusions could form the foundation for developing evidence-based recommendations for individualized exercise programs that alleviate depression in older adults. On the other hand, by revealing research gaps, the review results could encourage the formulation of research questions for further RCTs. This protocol has been published in the Prospero repository (PROSPERO 2022 CRD42022361418, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361418).

Pulmonary function assessment among conventional and organic cotton farmers exposed to pesticides in the Central-West region of Burkina Faso.

Respiratory diseases have been associated with the exposure of populations to some environmental pollutants such as pesticides. To assess effects of pesticides on farmers' respiratory health, this study aimed to evaluate the pulmonary function of cotton farmers exposed to synthetic and natural pesticides in the Central-West region of Burkina Faso. A cross-sectional study was conducted from June to July 2022 among 281 conventional and 189 organic cotton farmers. After collecting information on pesticide use conditions, pulmonary function tests (PFTs) were performed on each farmer according to the American Thoracic Society/European Respiratory Society guidelines, in order to assess chronic respiratory effects among cotton producers. Binary logistic regression was used to assess factors associated with the occurrence of ventilatory changes. Both conventional and organic cotton farmers reported similar chronic respiratory symptoms in different proportions. The main reported were rhinitis (54.45% conventional vs. 34.92% organic), chest pains (41.28% conventional vs. 23.81% organic), cough (33.45% conventional, 24.34% organic), breathlessness (31.67% conventional, 4.23% organic) (p<0.05). 16.18% and 27.50% of conventional male and female cotton farmers, respectively, had a restrictive defect. Among organic cotton farmers, 15.85% and 18.69%, respectively, of males and females had a restrictive defect. Furthermore, a significant increase in the predicted average percentage of FEV1/FVC ratio was observed among organic cotton farmers after salbutamol's use (p = 0.039). The type of cultivated cotton was not associated with ventilatory changes neither in the univariate analysis, nor in the multivariate analysis. Other factors such as farmers' age, BMI and insecticides use frequency per year were also important. Farmers who used insecticides more than 6 times per season had an increased risk of developing an obstructive defect (OR = 1.603; 95%CI: 0.484-5.309) compared to those who used them 6 times or less. Chronic respiratory signs and ventilatory impairments were found among conventional and, to our knowledge, for the first time among organic cotton producers. However, these health effects were more prevalent among conventional cotton farmers than organic ones.

#2015 Burosumab therapy in adult patients with X-linked hypophosphatemia: a three-year follow-up study

Abstract Background and Aims X-linked hypophosphatemic rickets (XLH) arises from mutations in the PHEX gene, resulting in elevated FGF23 levels, renal phosphate loss, hypophosphatemia, low vitamin D, heightened alkaline phosphatase (AP), and associated bone disorders. In challenging the conventional therapy of vitamin D and phosphate supplements, Burosumab, a monoclonal antibody against FGF23, has shown promise in normalizing phosphate and vitamin D levels in pediatric patients. However, its effectiveness in adult patients with established bone lesions remains an area of investigation. This study aims to present the three-year outcomes of Burosumab therapy on both biochemical and clinical aspects in adult XLH patients. Method The study assessed the efficacy of Burosumab in adult XLH patients (age &amp;gt;18, drug-naïve) before and continuously over three years post-therapy. Monthly assessments of biochemical parameters (phosphatemia, alkaline phosphatase, Tubular Maximum Reabsorption of Phosphate per Glomerular Filtration Rate, TMP/GFR) were conducted before the monthly administration of Burosumab, while clinical improvements were monitored every six months using established tests, including the six-minute walk test, UP and go timed test, and WOMAC Index. Burosumab was administered monthly at a consistent dosage of 1 mg/kg throughout the entire follow-up period. Results In a cohort of five genetically diagnosed XLH patients (average age 45 ± 10 years, average weight 60 ± 10 kg), the average monthly Burosumab dose was 60 ± 10 mg. Baseline values and subsequent changes in Ps, TMP/GFR, WOMAC Index, six-minute walk, and UP and go test are presented in Table 1 and Fig. 1. Importantly, no significant adverse events were reported during the initial year of treatment. Conclusion Burosumab therapy demonstrated excellent tolerability and yielded substantial improvements in biochemical parameters (Ps and TMP/GFR), maintaining stability over the entire three-year follow-up. Alkaline phosphatase levels, initially elevated, exhibited a progressive reduction in the second and third years, eventually reaching values within the normal range. Functional indices, reflective of enhanced strength (improved walk test and UP and go timed test) and diminished pain (optimal WOMAC test score), showcased notable improvements in the first year, persisting with stability during the follow-up period, with the exception of the walk test, which demonstrated a gradual and sustained enhancement. The findings suggest that Burosumab is a well-tolerated and effective therapeutic option for adult XLH patients. The observed reduction in alkaline phosphatase after a year of treatment implies a normalization of bone turnover, while the progressive improvement in the walk test indicates a sustained clinical enhancement likely associated with the chronic positive effects of maintaining biochemical stability.

#1437 Renal expression pattern of the relaxin receptor, RXFP1, and effects of the RXFP1 agonist, AZD5462, on renin in non-human primates and humans

Abstract Background and Aims RXFP1 is a G protein-coupled receptor (GPCR) for the pregnancy hormone, relaxin. While preclinical studies, performed primarily in rodent, describe beneficial effects of this pleiotropic peptide across several organ systems, there has been a disappointing lack of success in translating these observations into clinical benefit. To provide a potential pharmacological explanation accounting for this translational gap, the aim of this study was thus to thoroughly evaluate RXFP1 expression across species and tissues as well as to evaluate the renal-intrinsic effects of the RXFP1 agonist, AZD5462. Method Unbiased bioinformatic analysis of several gene expression databases was used as a first approach to compare RXFP1 tissue-level expression between rodent and human. Experimental validation was subsequently performed using scRNAseq, RNAscope and immunohistochemistry on mouse, rat, non-human primate (NHP) and human kidney. The putative renal target engagement effects of RXFP1 agonism were assessed by determining the acute and chronic effects of the RXFP1-selective small molecule agonist, AZD5462, on plasma renin concentrations in both NHPs and in a Phase 1 randomized, single-blind, placebo-controlled study in healthy humans. Results RXFP1 was identified as one of the most highly expressed GPCRs in human and NHP kidney glomeruli. Specifically, by multiple assays, we identified glomerular endothelial cells as the principal cell type expressing RXFP1. This observation is in stark contrast to mouse and rat kidney, where RXFP1 was not readily detected. AZD5462 administered orally to NHPs and healthy human participants elicited an early and sustained dose-dependent increase in plasma renin concentration, and in humans an additional decline in serum creatinine. Conclusion Human RXFP1 kidney glomerular expression is conserved with NHPs but not rodent, thus highlighting the translational and pharmacological challenges in studying RXFP1/relaxin biology across species. The concordant ability of AZD5462 to induce elevations in renin and reduction in serum creatinine, together with relaxin's reported renal-hemodynamic activity in humans, may underlie a previously unappreciated renal-intrinsic RXFP1 target engagement mechanism driving its hemodynamic and renal effects. The potential therapeutic benefits of RXFP1 agonism are the subject of on-going clinical trials in heart failure patients.

Neurotoxic effects of carbamazepine on the mosquitofish Gambusia affinis

In recent years, the presence of pharmaceuticals in the aquatic environment has gained a significant attention. Carbamazepine, a commonly prescribed antiepileptic drug, has been consistently found in aquatic environments at concentrations ranging from nanograms to micrograms, raising concerns about its potential negative impacts on aquatic organisms. The study examined the acute and chronic neurotoxic effects of environmentally relevant and sublethal concentrations of carbamazepine in the mosquitofish Gambusia affinis. After a 96-hour exposure period, the median lethal concentration (LC50) of carbamazepine for G. affinis was determined as 24 mg L − 1. For the current study, sublethal concentrations i.e., one-tenth (2.4 mg L − 1) and one-fifth (4.8 mg L − 1) of the LC50 value were chosen for assessing the neurotoxic effects along with the environmentally relevant concentration (13 ng L − 1). The research findings indicated that carbamazepine had a disruptive impact on the typical growth and behavior of the fish. During the acute exposure phase, physical deformities were observed in the fish, resulting in neonatal and postneonatal fatalities. Furthermore, the neurotoxic effects of carbamazepine were clearly demonstrated through alterations in various neurological parameters, including acetylcholinesterase, dopamine, gamma-aminobutyric acid, serotonin, monoamine oxidase, 5-hydroxyindole acetic acid, adrenaline, and nor-adrenaline. These findings raise concerns about the survival of fish populations in their natural environment.

The Use of Anabolic Steroids by Bodybuilders in the State of Sergipe, Brazil.

Bodybuilding, as a high-performance sport, requires regular strength and resistance exercises with the principal objective of increasing muscle hypertrophy. However, many bodybuilders resort to the use of anabolic-androgenic steroids (AASs) to improve their performance in a short period of time. This study employs a survey-type, cross-sectional, descriptive-analytical method to evaluate the profile of bodybuilding athletes in the State of Sergipe, Brazil, and verify the level of knowledge/awareness about the health risks and impacts resulting from the use of such substances. Finite- and convenience-type populations are assessed, including individuals of both sexes, aged older than 18 years, self-declared bodybuilding athletes residing in the State of Sergipe, Brazil, and participating in regional and/or state competitions. As a result, no significant relationships were determined between sex (p = 0.492), age (p = 0.460), family income (p = 0.141), and medical follow-up sessions. For the variables level of education and medical follow-up vs. no follow-up sessions, a significant result was achieved (p = 0.01), with 74.3% of individuals reporting having follow-up treatment and 25.7% responding that they had no follow-up treatment, a percentage representing the group that completed their higher education. The substances most used by the athletes were Sustanon 250 or Durateston, Nandrolone Decanoate (Deca or Deca-Durabolin), and Testosterone. The most-reported acute side effects were acne at 33.8% (n = 20), irritability at 32.1% (n = 19), alopecia (hair loss), and nervousness at 23.7% (n = 14). The most-reported chronic side effects were arterial hypertension at 36.0% (n = 9), liver disease at 28.0% (n = 7), and cancer (non-specific) at 8.0% (n = 2). We concluded that, regardless of the athletes' socioeconomic profiles, the use of AASs was high, with two or more substances being used in combination and for a prolonged period. Thus, it is necessary to promote awareness campaigns regarding the use of AASs and their effects on high-performance and recreational athletes.

Synthetic silica fibers of different length, diameter and shape: synthesis and interaction with rat (NR8383) and human (THP-1) macrophages in vitro, including chemotaxis and gene expression profile

BackgroundInhalation of biopersistent fibers like asbestos can cause strong chronic inflammatory effects, often resulting in fibrosis or even cancer. The interplay between fiber shape, fiber size and the resulting biological effects is still poorly understood due to the lack of reference materials.ResultsWe investigated how length, diameter, aspect ratio, and shape of synthetic silica fibers influence inflammatory effects at doses up to 250 µg cm-2. Silica nanofibers were prepared with different diameter and shape. Straight (length ca. 6 to 8 µm, thickness ca. 0.25 to 0.35 µm, aspect ratio ca. 17:1 to 32:1) and curly fibers (length ca. 9 µm, thickness ca. 0.13 µm, radius of curvature ca. 0.5 µm, aspect ratio ca. 70:1) were dispersed in water with no apparent change in the fiber shape during up to 28 days. Upon immersion in aqueous saline (DPBS), the fibers released about 5 wt% silica after 7 days irrespectively of their shape. The uptake of the fibers by macrophages (human THP-1 and rat NR8383) was studied by scanning electron microscopy and confocal laser scanning microscopy. Some fibers were completely taken up whereas others were only partially internalized, leading to visual damage of the cell wall. The biological effects were assessed by determining cell toxicity, particle-induced chemotaxis, and the induction of gene expression of inflammatory mediators.ConclusionsStraight fibers were only slightly cytotoxic and caused weak cell migration, regardless of their thickness, while the curly fibers were more toxic and caused significantly stronger chemotaxis. Curly fibers also had the strongest effect on the expression of cytokines and chemokines. This may be due to the different aspect ratio or its twisted shape.

Single episode of moderate to severe traumatic brain injury leads to chronic neurological deficits and Alzheimer's-like pathological dementia.

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions.

Aortic Injury Induced by Benzo(a)pyrene and Atherogenic Diet Increased Hepatic FGF21 Expression in C57BL/6J Mice

Background: Benzo(a)pyrene (BaP), an environmental toxicant and endocrine disruptor, has been shown to exacerbate atherosclerosis when combined with a high-fat diet. Fibroblast Growth Factor-21 (FGF21), a novel hormone with anti-atherosclerotic properties, is associated with the presence of atherosclerosis and reduces plaque formation in experimental animals. Objectives: The present study aimed to investigate the chronic effect of BaP injection on hepatic FGF21 expression, as an anti-atherosclerotic hormone, in mice fed with or without an atherogenic diet (AtD). Methods: Eighteen C57BL/6J male mice (6 weeks) were randomly divided into six groups based on the dosage and diet. Blood samples were collected, and serum cholesterol, triglyceride, HDL-C, LDL-C, and glucose levels were measured. FGF21 expression was assessed by quantitative real-time PCR. Atherosclerotic lesions in mice were studied with Oil Red O (ORO) staining. Results: Benzo(a)pyrene causes a significant increase in liver FGF21 expression in a dose-dependent manner, and BaP co-exposure with AtD leads to a further increase in FGF21 expression. Additionally, the addition of BaP to AtD significantly increased the serum glucose, cholesterol, and LDL-C levels and accelerated the formation of atherosclerotic lesions. Besides, our findings showed that there is a significant positive correlation between FGF21 expression and glucose, cholesterol, LDL-C, and ORO-positive areas. Conclusions: Our findings revealed that BaP increases the expression of endogenous FGF21 in treated animals as a compensatory response to protect the heart from atherosclerosis induced by BaP and AtD.

Analyses of industrial air pollution and long-term health risk using different dispersion models and WRF physics parameters

AbstractThis study consists of three main sections. The first section delves into a performance analysis centered around modeling PM10, NOx, and CO emissions from a cement factory. It examines the effectiveness of various factors, including meteorological data, physics models, and air quality dispersion models, in producing accurate results for atmospheric simulations. The second section covers the dispersion direction and concentrations obtained by visualizing the dispersion maps. The third section covers an analysis of heavy metals emitted from the facility, taking into account potential risks in the region such as cancer, acute and chronic effects, and long-term respiratory risks. This study made use of meteorological models (WRF, AERMET, and CALMET), air quality dispersion models (AERMOD and CALPUFF), a health risk analysis model (HARP), and various sub-models (MMIF and CALWRF). Satellite meteorological data were obtained from NCEP and ERA, with the majority of meteorological data based on the Global Data Assimilation System (GDAS)/Final Operational Global Analysis (FNL) from Global Tropospheric Analyses and Forecast Grids used for the WRF model. In the daily results, AERMOD showed the highest concentration values, but CALPUFF had greater concentrations throughout the annual period. The winter season had the highest concentrations of pollutants. Although there are differences among the physics models used in this research, the conclusions produced are consistent. Analysis of the data from the HARP model suggested that cancer risk levels exceeded the threshold of one person per million. However, the proportion of exceedance instances is rather small in comparison to the receptor points.

Levels of high-sensitive troponin T and mid-regional pro-adrenomedullin after COVID-19 vaccination

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Federal Ministry of Education and Research. Background/Introduction To increase vaccine safety, adverse events of COVID-19 vaccines are continuously monitored. This also includes rare complications of the cardiovascular system. However, it has so far been scarcely investigated whether chronic and subtle, clinically inapparent myocardial and/or vascular injury occurs in a COVID-19 vaccinated population on a broader basis. Purpose The aim of this study was to analyse chronic and subclinical adverse effects of COVID-19 vaccines on the cardiovascular system. Vaccine-associated myocardial involvement was examined by measuring high-sensitive troponin T (hsTnT) while mid-regional pro-adrenomedullin (MR-proADM) levels were evaluated to assess endothelial dysfunction. Methods This was a prospective observational study with a vulnerable population of healthcare workers (HCWs) and elderly (&amp;gt; 70 years) patients who were vaccinated with either the ChAdOx1 nCov-19 adenoviral vector vaccine (AZ) and the BNT162b2 mRNA vaccine (BNT), or with BNT/BNT between the 12th of January and 30th of November 2021 (Figure 1). HsTnT and MR-proADM was measured in blood samples at three visits (V1: 1st baseline, immediately before vaccination; V2: 3-4 weeks after 1st vaccination; V3: 3-4 weeks after 2nd vaccination). HsTnT levels were further compared with a healthy reference cohort. Results 120 participants were included (V1=119, V2=120, V3=120). 50 (41.7%) received AZ/BNT. 70 (58.3%) were vaccinated with BNT/BNT of whom 20 (16.7%) were elderly and 50 (41.7%) were HCWs. Median hsTnT levels were at 4ng/L, 5ng/L and 4ng/L (V1-V3) for AZ/BNT and at 6ng/L, 6ng/L and 6ng/L (V1-V3) for BNT/BNT, respectively (Figure 2). Levels of MR-proADM were 0.43nmol/L, 0.46nmol/L and 0.44nmol/L (V1-V3) in the AZ/BNT cohort and 0.49nmol/L, 0.43nmol/L and 0.49nmol/L in the BNT/BNT group. Change of hsTnT and MR-proADM values between visits did not show significant increases. Two cases had a transient (7ng/L, 19ng/L, 5ng/L; male, 29 years) or permanent (15ng/L, 21ng/L, 25ng/L; male, 37 years) increase in hsTnT levels, exceeding the upper reference limit (≥ 14ng/L). Compared to the reference population (n=300), median hsTnT was significantly higher at all visits for both vaccination groups (p&amp;lt;0.05), without significant differences between the AZ/BNT and BNT/BNT cohorts. Conclusion(s) With two individual exceptions, no overall chronic myocardial injury or endothelial involvement was observed up to 4 weeks after the 2nd SARS-CoV-2 vaccination when comparing hsTnT and MR-proADM after both vaccinations to baseline values.Figure 1Vaccination scheme.Figure 2.hsTnT values at V1-V3.

Chronic Effects of Waterborne Silver on the Physiology and Reproduction of the Manila Clam Ruditapes philippinarum

Chronic Effects of Waterborne Silver on the Physiology and Reproduction of the Manila Clam Ruditapes philippinarum

Mimicking chronic alcohol effects through a controlled and sustained ethanol release device

Alcohol consumption, a pervasive societal issue, poses considerable health risks and socioeconomic consequences. Alcohol-induced hepatic disorders, such as fatty liver disease, alcoholic hepatitis, chronic hepatitis, liver fibrosis, and cirrhosis, underscore the need for comprehensive research. Existing challenges in mimicking chronic alcohol exposure in cellular systems, attributed to ethanol evaporation, necessitate innovative approaches. In this study, we developed a simple, reusable, and controllable device for examining the physiological reactions of hepatocytes to long-term alcohol exposure. Our approach involved a novel device designed to continuously release ethanol into the culture medium, maintaining a consistent ethanol concentration over several days. We evaluated device performance by examining gene expression patterns and cytokine secretion alterations during long-term exposure to ethanol. These patterns were correlated with those observed in patients with alcoholic hepatitis. Our results suggest that our ethanol-releasing device can be used as a valuable tool to study the mechanisms of chronic alcohol-mediated hepatic diseases at the cellular level. Our device offers a practical solution for studying chronic alcohol exposure, providing a reliable platform for cellular research. This innovative tool holds promise for advancing our understanding of the molecular processes involved in chronic alcohol-mediated hepatic diseases. Future research avenues should explore broader applications and potential implications for predicting and treating alcohol-related illnesses.

Disposable indicator card for personal monitoring of solar exposure

Although the Earths atmosphere provides substantial reduction of the incident radiant power in the most harmful spectral ranges, excessive exposure of untrained and/or unprotected human skin to solar radiation can easily result into acute and chronic adverse effects onto human skin. In order to reduce these effects, a simple tool for monitoring the incident radiant dose is proposed. We report on the design, development, lab scale fabrication, calibration and the roll-to-roll printing production of a photosensitive indicator cards intended for personal monitoring of solar exposure to which the user has been subjected. Two types of cards are being discussed. The first one is supposed as high sensitive one with a dose response to 1 and 2 SEDs, the second one is a less sensitive with a dose response to 3 and 4 SEDs. The calibration of the cards was performed with polychromatic simulated solar radiation without determining the spectral response, therefore we refer to the device as indicator card, not dosimeters. Moreover, properties of the photosensitive formulation employed for the fabrication of the indicator are presented alongside with the calibration of the printed indicator to dermatologically relevant values of the received solar exposure dose. Special attention is also paid to the large-scale practical production of such indicators by the roll-to-roll printing technology. Mechanical properties, stability, durability, practical utilisation, and other features are critically assessed.

An Integrated Testing Strategy (ITS) to assess the environmental compatibility of wood protection techniques

To quantify the possible impact of different wood protection techniques on the aquatic environment, we applied a tiered Integrated Testing Strategy (ITS) on leachates obtained from untreated (UTW) Norway spruce (Picea abies), specimens treated with a copper-ethanolamine-based preservative solution, complying with the Use Class 3 (UC3), and specimens thermally modified (TM). Different maturation times in water were tested to verify whether toxicant leaching is time-dependent. Tier I tests, addressing acute effects on Aliivibrio fischeri, Raphidocelis subcapitata, and Daphnia magna, evidenced that TM toxicity was comparable or even lower than in UTW. Conversely, UC3 significantly affected all species compared to UTW, also after 30 days of maturation in water, and was not considered an environmentally acceptable wood preservation solution. Tier II (effects on early-life stages of Lymnea auricularia) and III (chronic effects on D. magna and L. auricularia) performed on UTW and TM confirmed the latter as an environmentally acceptable treatment, with increasing maturation times resulting in decreased adverse effects. The ITS allowed for rapid and reliable identification of potentially harmful effects due to preservation treatments, addressed the choice for a less impacting solution, and can be effective for manufacturers in identifying more environmentally friendly solutions while developing their products.

Radiotherapy Related Bowel and Bladder Toxicity after Prostate Cancer Irradiation

Background: Pelvic radiotherapy is a primary treatment modality for organ-confined prostate cancer and early-stage endometrial cancer. While effective in improving survival rates and reducing recurrence, it is associated with a range of side effects that can impact patient quality of life. Objective: The study aimed to assess the incidence, management, and resolution of acute and chronic side effects of pelvic radiotherapy in prostate and endometrial cancer patients, focusing on bowel and bladder functions. Methods: This single-center, observational study included 50 patients diagnosed with prostate or endometrial cancer who underwent pelvic radiotherapy with a dose of 66-70 Gy using a four-field technique on a linear accelerator. Patients were assessed for bladder and bowel dysfunction, with follow-up at 6, 12, and 18 months post-treatment. Statistical analysis involved univariate weighted distribution of response frequencies and paired t-tests for ordinal scale scores, using SPSS version 25 for data analysis. Results: Of the participants, 22% experienced dysuria, 64% reported bladder outlet obstruction, and 20% had constipation. Acute bowel symptoms like diarrhea occurred in 32%, and chronic proctitis developed in 22% of patients. Urinary symptoms appeared by the third week and generally resolved within weeks; however, bowel symptoms persisted longer but returned to baseline by 18 months post-treatment. Approximately 70% of patients reported good tolerance to radiotherapy. Conclusion: Pelvic radiotherapy is effective in treating prostate and endometrial cancers but requires management of transient side effects to improve patient outcomes. Advanced radiotherapy techniques such as IMRT and 3D CRT have shown potential in reducing these side effects, emphasizing the need for continuous technological advancements and patient-centered care in radiotherapy.