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    Guidelines for Studying Diverse Types of Compound Weather and Climate Events

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    Compound weather and climate events are combinations of climate drivers and/or hazards that contribute to societal or environmental risk. Studying compound events often requires a multidisciplinary approach combining domain knowledge of the underlying processes with, for example, statistical methods and climate model outputs. Recently, to aid the development of research on compound events, four compound event types were introduced, namely (a) preconditioned, (b) multivariate, (c) temporally compounding, and (d) spatially compounding events. However, guidelines on how to study these types of events are still lacking. Here, we consider four case studies, each associated with a specific event type and a research question, to illustrate how the key elements of compound events (e.g., analytical tools and relevant physical effects) can be identified. These case studies show that (a) impacts on crops from hot and dry summers can be exacerbated by preconditioning effects of dry and bright springs. (b) Assessing compound coastal flooding in Perth (Australia) requires considering the dynamics of a non-stationary multivariate process. For instance, future mean sea-level rise will lead to the emergence of concurrent coastal and fluvial extremes, enhancing compound flooding risk. (c) In Portugal, deep-landslides are often caused by temporal clusters of moderate precipitation events. Finally, (d) crop yield failures in France and Germany are strongly correlated, threatening European food security through spatially compounding effects. These analyses allow for identifying general recommendations for studying compound events. Overall, our insights can serve as a blueprint for compound event analysis across disciplines and sectors.Plain Language Summary: Many societal and environmental impacts from events such as droughts and storms arise from a combination of weather and climate factors referred to as a compound event. Considering the complex nature of these high-impact events is crucial for an accurate assessment of climate-related risk, for example to develop adaptation and emergency preparedness strategies. However, compound event research has emerged only recently, therefore our ability to analyze these events is still limited. In practice, studying compound events is a challenging task, which often requires interaction between experts across multiple disciplines. Recently, compound events were divided into four types to aid the framing of research on this topic, but guidelines on how to study these four types are missing. Here, we take a pragmatic approach and—focusing on case studies of different compound event types—illustrate how to address specific research questions that could be of interest to users. The results allow identifying recommendations for compound event analyses. Furthermore, through the case studies, we highlight the relevance that compounding effects have for the occurrence of landslides, flooding, vegetation impacts, and crop failures. The guidelines emerged from this work will assist the development of compound event analysis across disciplines and sectors

    Dietary Exposure and Risk Assessment of Aflatoxin M1 for Children Aged 1 to 9 Years Old in Serbia

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    The present study was conducted to estimate the exposure and characterize the risk for the child population of Serbia to Aflatoxin M1 (AFM1) from milk and milk-based food. A total of 3404 samples comprising milk and different milk-based food samples were collected from various regions of Serbia from 2017 to 2019. Evaluation of AFM1 exposure was carried out using the deterministic method, whereas risk characterization was evaluated using the margin of exposure (MOE) and the risk of hepatocellular carcinoma (HCC). Detection rates for AFM1 in milk and milk-based food samples ranged between 2% and 79%, with the highest incidence (79%) and mean level (22.34 ± 0.018 ng kg−1) of AFM1 being detected in pasteurized and UHT milk. According to the three consumption estimates, the values of estimated daily intake (EDI) were higher for toddlers as compared with children aged 3–9 years. Children aged 1–3 years had the highest risk of exposure to AFM1 in milk, with an estimated daily intake of 0.164 and 0.193 ng kg−1 bw day−1 using lower bound (LB) and upper bound (UB) exposure scenarios, respectively. Such difference could result from the higher consumption to weight in younger children. Based on the estimated daily intake (EDI) found in this study, the risk of AFM1 exposure due to consumption of milk and milk-based food was low since the MOE values obtained were >10,000. In addition, the risk of HCC cases/year/105 individuals of different age groups showed that the value of HCC, using potency estimates of 0.0017 (mean), was maximum (0.00034) in the age group 1–3 years, which indicates no health risk for the evaluated groups. The present study revealed the importance of controlling and preventing AFM1 contamination in milk through continuous monitoring and regular inspection to reduce the risk of AFM1 exposure, especially in children

    Effects of Resistance Training With Constant, Inertial, and Combined Loads on Muscle Power and Strength Output

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    The aim of this study was to investigate the resistance-specific gains in muscle power and strength (1RM) following the training of maximum bench-press throws (BPT) against constant, inertial, and combined resistance. Forty-eight male participants (age 20.5 ± 2.0 years) were randomly assigned to the constant, inertial, combined resistance, or control group. Participants underwent 8 weeks of training of BPT against the loads that corresponded to the different effects of mass of 40 kg (∼50% of 1RM). The gains in average and maximum power, and 1RM were significant in all experimental groups (P 0.1). Relative gains in the average (26.3 ± 9.8%) and maximum power (25.2 ± 9.8%) were larger than that in the 1RM (mean 7.2 ± 6.9%; both P < 0.001). The gains in the average (F4, 66 = 6.0; P < 0.01) and maximum power (F4, 66 = 4.7; P < 0.01) were higher when tested against the training-specific resistance than when tested against the remaining two resistance types. Differences in 1RM among experimental groups were not significant (P = 0.092). The most important and rather novel finding of the study is that the training against the weight and inertial resistance, and their combination results in resistance-specific gains in muscle power, although the overall gains muscle strength and power remain comparable across the training protocols

    Postnatal ocular toxoplasmosis in immunocompetent patients

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    Introduction: Ocular toxoplasmosis is the most common cause of infectious posterior uveitis worldwide. It can be prenatal or postnatal in origin. Despite estimations that postnatal ocular toxoplasmosis is more prevalent, only several cases of proven postnatal ocular toxoplasmosis have been reported in non-epidemic settings. Here, the clinical evolution of ocular toxoplasmosis of conclusively proven postnatal origin in immunocompetent patients is reported.Methodology: Postnatal ocular toxoplasmosis was diagnosed based on clinical diagnosis supported by the longitudinal detection of Toxoplasma gondii-specific IgG, IgM and IgA antibodies in the serum as well as by direct detection of the parasite (bioassay) and/or its DNA (real-time PCR) in aqueous humor.Results: Three cases involved adults in whom ocular toxoplasmosis developed during primary T. gondii infection, as part of the clinical presentation in two and as the sole manifestation in one patient. The fourth patient was a case of inactive ocular toxoplasmosis in a 14-year-old boy, where postnatal infection was confirmed by exclusion of maternal infection. The causative parasite strain was genotyped in only one case and it belonged to genotype II, the dominant type in Europe. One patient acquired the infection in Africa, suggesting an atypical strain.Conclusions: The distinction between prenatal and postnatal ocular toxoplasmosis is only possible in particular clinical situations, and requires extensive laboratory investigation. Genotyping of the parasite strain involved may be important, particularly if atypical strains are suspected, requiring tailored treatment approaches

    The Novel Single-Stroke Kayak Test: Can It Discriminate Between 200-m and Longer-Distance (500-and 1000-m ) Specialists in Canoe Sprint?

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    Purpose: To test whether the force-velocity (F-V) relationship obtained during a specific single-stroke kayak test (SSKT) and during nonspecific traditional resistance-training exercises (bench press and prone bench pull) could discriminate between 200-m specialists and longer-distance (500- and 1000-m) specialists in canoe sprint. Methods: A total of 21 experienced male kayakers (seven 200-m specialists and 14 longer-distance specialists) participated in this study. After a familiarization session, kayakers came to the laboratory on 2 occasions separated by 48 to 96 hours. In a randomized order, kayakers performed the SSKT in one session and the bench press and bench pull tests in another session. Force and velocity outputs were recorded against 5 loads in each exercise to determine the F-V relationship and related parameters (maximum force, maximum velocity, F-V slope, and maximum power). Results: The individual F-V relationships were highly linear for the SSKT (r = .990 [.908, .998]), bench press (r = .993 [.974, .999]), and prone bench pull (r = .998 [.992, 1.000]). The F-V relationship parameters (maximum force, maximum velocity, and maximum power) were significantly higher for 200-m specialists compared with longer-distance specialists (all Ps lt = .047) with large effect sizes ( gt = 0.94) revealing important practical differences. However, no significant differences were observed between 200-m specialists and longer-distance specialists in the F-V slope (P gt = .477). Conclusions: The F-V relationship assessed during both specific (SSKT) and nonspecific upper-body tasks (bench press and bench pull) may distinguish between kayakers specialized in different distances

    Biocompatibility Study of a New Dental Cement Based on Hydroxyapatite and Calcium Silicates: Focus on Liver, Kidney and Spleen Tissue Effects

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    The effects of a new material based on hydroxyapatite and calcium silicates, named ALBO-MPCA, were investigated on the liver, kidney and spleen. The material was administrated orally for 120 days in an in vivo model in Wistar rats, and untreated animals served as a control. Hematological and biochemical blood parameters were analyzed. Qualitative histological analysis of tissues, change in mitotic activity of cells, and histological characteristics was conducted, as well as quantitative stereological analysis of parenchymal cells, blood sinusoids, and connective tissues. Additionally, the protein expressions of Ki67 and CD68 markers were evaluated. Histological analysis revealed no pathological changes after the tested period. It showed the preservation of the architecture of blood sinusoids and epithelial cells and the presence of mitosis. Additionally, the significantly increased number of the Ki67 in the presence of ALBO-MPCA confirmed the proliferative effect of the material noticed by stereological analysis, while immunoreactive CD68 positive cells did not differ between groups. The study showed non-toxicity of the tested material based on the effects on the hematological, biochemical, and observed histological parameters; in addition, it showed evidence of its biocompatibility. These results could be the basis for further steps toward the application of tested materials in endodontics

    Resveratrol Protects Cardiac Tissue in Experimental Malignant Hypertension Due to Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Properties

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    Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-β and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension

    Memorable Food: Fighting Age-Related Neurodegeneration by Precision Nutrition

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    Healthcare systems worldwide are seriously challenged by a rising prevalence of neurodegenerative diseases (NDDs), which mostly, but not exclusively, affect the ever-growing population of the elderly. The most known neurodegenerative diseases are Alzheimer's (AD) and Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, but some viral infections of the brain and traumatic brain injury may also cause NDD. Typical for NDD are the malfunctioning of neurons and their irreversible loss, which often progress irreversibly to dementia and ultimately to death. Numerous factors are involved in the pathogenesis of NDD: genetic variability, epigenetic changes, extent of oxidative/nitrosative stress, mitochondrial dysfunction, and DNA damage. The complex interplay of all the above-mentioned factors may be a fingerprint of neurodegeneration, with different diseases being affected to different extents by particular factors. There is a voluminous body of evidence showing the benefits of regular exercise to brain health and cognitive functions. Moreover, the importance of a healthy diet, balanced in macro- and micro-nutrients, in preventing neurodegeneration and slowing down a progression to full-blown disease is evident. Individuals affected by NDD almost inevitably have low-grade inflammation and anomalies in lipid metabolism. Metabolic and lipid profiles in NDD can be improved by the Mediterranean diet. Many studies have associated the Mediterranean diet with a decreased risk of dementia and AD, but a cause-and-effect relationship has not been deduced. Studies with caloric restriction showed neuroprotective effects in animal models, but the results in humans are inconsistent. The pathologies of NDD are complex and there is a great inter-individual (epi)genetic variance within any population. Furthermore, the gut microbiome, being deeply involved in nutrient uptake and lipid metabolism, also represents a pillar of the gut microbiome–brain axis and is linked with the pathogenesis of NDD. Numerous studies on the role of different micronutrients (omega-3 fatty acids, bioactive polyphenols from fruit and medicinal plants) in the prevention, prediction, and treatment of NDD have been conducted, but we are still far away from a personalized diet plan for individual NDD patients. For this to be realized, large-scale cohorts that would include the precise monitoring of food intake, mapping of genetic variants, epigenetic data, microbiome studies, and metabolome, lipidome, and transcriptome data are needed

    Myeloid-Derived Suppressor Cells and Mesenchymal Stem/Stromal Cells in Myeloid Malignancies

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    Myeloid malignancies arise from an altered hematopoietic stem cell and mainly comprise acute myeloid leukemia, myelodysplastic syndromes, myeloproliferative malignancies, and chronic myelomonocytic leukemia. Myeloid neoplastic leukemic cells may influence the growth and differentiation of other hematopoietic cell lineages in peripheral blood and bone marrow. Myeloid-derived suppressor cells (MDSCs) and mesenchymal stromal cells (MSCs) display immunoregulatory properties by controlling the innate and adaptive immune systems that may induce a tolerant and supportive microenvironment for neoplasm development. This review analyzes the main features of MDSCs and MSCs in myeloid malignancies. The number of MDSCs is elevated in myeloid malignancies exhibiting high immunosuppressive capacities, whereas MSCs, in addition to their immunosuppression contribution, regulate myeloid leukemia cell proliferation, apoptosis, and chemotherapy resistance. Moreover, MSCs may promote MDSC expansion, which may mutually contribute to the creation of an immuno-tolerant neoplasm microenvironment. Understanding the implication of MDSCs and MSCs in myeloid malignancies may favor their potential use in immunotherapeutic strategies

    Zinc Deficiency, Plasma Fatty Acid Profile and Desaturase Activities in Hemodialysis Patients: Is Supplementation Necessary?

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    Background: Desaturation and elongation are critical processes in endogenous metabolic fatty acid pathways. Zinc (Zn) is a cofactor for desaturases and elongases enzymes. There is limited evidence regarding the relationships between biomarkers of Zn status, nutritional intake, plasma phospholipid fatty acid profile and clinical outcomes among patients undergoing hemodialysis (HD). Objective: To examine the relationships between dietary and serum levels of Zn and Cu/Zn ratio and to explore associations of these micronutrients with PUFA profile and estimated desaturase and elongase enzyme activities in serum phospholipids among HD patients. Methods: This study included 40 adult patients undergoing hemodialysis treatment. Repeated 24-h recalls were applied for dietary intake assessment. Serum concentration of Zn and Cu were determined using inductively coupled plasma mass spectrometry and fatty acid composition by gas-liquid chromatography. Desaturase and elongase activities were calculated from product-precursor fatty acid ratios. Results: Inadequate dietary Zn intake was found in 55% of HD patients. They all had serum Zn concentration below the reference value of 60 μg/dL (mean 38.8 ± 7.72 μg/dL). Adequate zinc intake was accompanied with significantly higher intake of energy, total fats, SFA, MUFA and proteins. There was no correlation between Zn serum status and Zn intake estimates. Serum Cu/Zn ratio was high, (2.76 ± 0.68), directly and significantly associated with HD period, CRP, BMI, VFA, and inversely with Kt/V, albumin, iron, and iPTH. The n-6/n-3 ratio in plasma phospholipids was elevated (12.25 ± 3.45) and patients with inadequate Zn intake had lower n-3 PUFA intake and status compared to those with adequate intake. Serum Zn concentrations were inversely correlated with linoleic/dihomo-γ-linolenic acid ratio (LA/DGLA) (p = 0.037), related to D6-desaturase activity (p = 0.033) and directly with DGLA relative abundances (p = 0.024). Cu status was inversely associated with EPA level (p = 0.03) and estimates of elongase activity (p = 0.001). Furthermore, positive relationship was found between the Cu/Zn ratio and determined elongase value (p = 0.01). Conclusion: Findings of this study underpin the high prevalence of Zn deficiency and inadequate n-3 PUFA intake and status among subjects undergoing HD. The results obtained indicate that the assessment of Zn status should be a standard parameter of nutritional status screening in HD patients while emphasizing the importance of Cu/Zn determination. Although further research is warranted, Zn and-n-3 PUFA supplementation in HD patients might be beneficial for the prevention and attenuation of adverse health outcomes

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