Human Observational Studies Research Articles

Perturbations in gut microbiota composition in patients with polycystic ovary syndrome: a systematic review and meta-analysis

BackgroundThe results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women.MethodsLiterature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge’s g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I2) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed.ResultsTwenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = − 0.27; 95% CI, − 0.37 to − 0.16; phylogenetic diversity: SMD = − 0.39; 95% CI, -− 0.74 to − 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria.ConclusionsGut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk.Trial registrationPROSPERO registration: CRD42021285206, May 22, 2023.

Evaluation of In-vitro Antioxidant Potential of Bryophillum pinnatum Leaf Juice in Phenyl Hydrazine Treated Goat Erythrocytes

Phytochemicals are known to contain a high concentration of therapeutically active principles, which, when consumed in sufficient quantities, can have drug-like effects. Bryophillum pinnatum (Lam.) is a succulent-ethno medicinal xerophyte with a long history of use in traditional Indian medicine. Because reactive oxygen species are the most common etiological factor in many degenerative diseases, controlling them with antioxidants may both treat and prevent disease progression. The current study will look at the ability of fresh leaf juice of Bryophillum pinnatum (Lam.) (FLJBP) to prevent oxidative injury and subsequent hemolysis in goat erythrocytes as a model test system. The catalytic activity of membrane bound enzymes like sodium potassium-ATPase, Ach-Ease, and metabolic enzymes like hexokinase, as well as the NO concentration in goat RBCs, were measured. Phenyl hydrazine was used first, followed by FLJBP at concentrations of 20, 40, 60, 80, and 100g/ml. A dose-dependent (PHZ) increase in Pi liberation by hexokinase and Na+/K+ ATPase, as well as increased formation of thiocholine iodide and enhanced NO scavenging potential, has indicated that flip has good anti-oxidant and anti-haemolytic activity. To record the functional food status of Bryophillum pinnatum (Lam.) species, a more rigorous and stringent battery of pharmacological, phytochemical, and bio analytical studies, followed by observational studies in humans, will be conducted.

Ambient temperature and mental health: a systematic review and meta-analysis

Increasing evidence indicates that ambient outdoor temperature could affect mental health, which is especially concerning in the context of climate change. We aimed to comprehensively analyse the current evidence regarding the associations between ambient temperature and mental health outcomes. We did a systematic review and meta-analysis of the evidence regarding associations between ambient outdoor temperature and changes in mental health outcomes. We searched WebOfScience, Embase, PsychINFO, and PubMed for articles published from database origin up to April 7, 2022. Eligible articles were epidemiological, observational studies in humans of all ages, which evaluated real-world responses to ambient outdoor temperature, and had mental health as a documented outcome; studies of manipulated or controlled temperature or those with only physical health outcomes were excluded. All eligible studies were synthesised qualitatively. If three or more studies reported the same or equivalent effect statistics and if they had equivalent exposure, outcome, and metrics, the studies were pooled in a random-effects meta-analysis. The risk of bias for individual studies was assessed using the Newcastle-Ottawa Scale. The quality of evidence across studies was assessed using the Office of Health Assessment and Translation (OHAT) approach. 114 studies were included in the systematic review, of which 19 were suitable for meta-analysis. Three meta-analyses were conducted for suicide outcomes: a 1°C increase in mean monthly temperature was associated with an increase in incidence of 1·5% (95% CI 0·8-2·2, p<0·001; n=1 563 109, seven effects pooled from three studies); a 1°C increase in mean daily temperature was associated with an increase in incidence of 1·7% (0·3-3·0, p=0·014; n=113 523, five effects pooled from five studies); and a 1°C increase in mean monthly temperature was associated with a risk ratio of 1·01 (95% CI 1·00-1·01, p<0·001; n=111 794, six effects pooled from three studies). Three meta-analyses were conducted for hospital attendance or admission for mental illness: heatwaves versus non-heatwave periods were associated with an increase in incidence of 9·7% (95% CI 7·6-11·9, p<0·001; n=362 086, three studies); the risk ratio at the 99th percentile of daily mean temperature compared with the 50th percentile was 1·02 (95% CI 1·01-1·03, p=0·006; n=532 296, three studies); and no significant association was found between a 10°C increase in daily mean temperature and hospital attendance. In a qualitative narrative synthesis, we found that ambient outdoor temperature (including absolute temperatures, temperature variability, and heatwaves) was positively associated with attempted and completed suicides (86 studies), hospital attendance or admission for mental illness (43 studies), and worse outcomes for community mental health and wellbeing (19 studies), but much of the evidence was of low certainty with high heterogeneity. Increased temperature and temperature variability could be associated with increased cases of suicide and suicidal behaviour, hospital attendance or admission for mental illness, and poor community health and wellbeing. Climate change is likely to increase temperature anomalies, variability, and heatwaves as well as average temperatures; as such, health system leaders and policy makers must be adequately prepared and should develop adaptation strategies. More high-quality, standardised research is required to improve our understanding of these effects. None.

Plant Sterols and Plant Stanols in Cholesterol Management and Cardiovascular Prevention.

Atherosclerotic cardiovascular disease (ASCVD) remains the major mortality cause in developed countries with hypercholesterolaemia being one of the primary modifiable causes. Lifestyle intervention constitutes the first step in cholesterol management and includes dietary modifications along with the use of functional foods and supplements. Functional foods enriched with plant sterols/stanols have become the most widely used nonprescription cholesterol-lowering approach, despite the lack of randomized trials investigating their long-term safety and cardiovascular efficacy. The cholesterol-lowering effect of plant-sterol supplementation is well-established and a potential beneficial impact on other lipoproteins and glucose homeostasis has been described. Nevertheless, experimental and human observational studies investigating the association of phytosterol supplementation or circulating plant sterols with various markers of atherosclerosis and ASCVD events have demonstrated controversial results. Compelling evidence from recent genetic studies have also linked elevated plasma concentrations of circulating plant sterols with ASCVD presence, thus raising concerns about the safety of phytosterol supplementation. Thus, the aim of this review is to provide up-to-date data on the effect of plant sterols/stanols on lipid-modification and cardiovascular outcomes, as well as to discuss any safety issues and practical concerns.

Influence of abutment macro- and micro-geometry on morphologic and morphometric features of peri-implant connective tissue.

The aim of the present human observational study is to provide morphologic and morphometric analysis of peri-implant connective tissue next to abutments with divergent or convergent macro-geometry and different surface micro-characteristics. Thirty patients were rehabilitated with single implants in the posterior area and one out of three different healing abutments with a one-stage technique: machined divergent abutment (DIV-MAC), machined convergent abutment (CONV-MAC) or convergent abutment with ultrathin threaded surface (CONV-UTM). At 3 months postimplant insertion, peri-implant soft tissue was harvested; the following outcomes were investigated: histomorphometry (vertical width of connective and epithelial components) as detected by histology and polarized light; and connective tissue vertical width and 3D organization as detected by synchrotron-based high-resolution phase-contrast-based tomography (PhC-μCT). Significant differences in connective tissue vertical dimension (aJE-AM) were found between DIV-MAC and both CONV-MAC and CONV-UTM, both by histology and PhC-μCT, with significantly higher values for the last two groups. Moreover, 2D histological analysis did not find significant differences in the junctional epithelium vertical dimension (PM-aJE). Importantly, PhC-μCT analysis revealed, at 3D level, significant greater amount and density of collagen bundles for CONV-UTM compared with the other two groups. Convergent abutment profiles, regardless of their surface micro-geometry, seem to favor axial development of peri-implant connective tissue. Moreover, ultrathin threaded surfaces seem associated with denser and greater connective tissue organization, which might improve peri-implant soft tissue seal.

Maternal pesticide exposure and risk of preterm birth: A systematic review and meta-analysis

BackgroundMaternal pesticide exposure might be associated with adverse pregnancy outcomes through triggering inflammation and oxidative stress and disrupting endocrine functions. Yet the association between prenatal pesticide exposure and risk of preterm birth remains inconclusive. ObjectivesTo conduct a systematic review and meta-analysis of human observational studies using the Office of Health Assessment and Translation (OHAT) framework to explore the association of per ten-fold increase of pesticide concentrations in maternal biological samples during pregnancy with risk of preterm birth and length of gestational age at birth. Data sourceFive English (PubMed, Embase, Cochrane Library, Web of Science and Scopus) and 3 Chinese databases (China national knowledge infrastructure (CNKI), Wanfang Data, and Chinese Biomedical Literature Database (CBM)) were searched till Jan 18th, 2023. Study eligibility criteria, participants, and interventionsTo be included, pesticide exposure should be measured in maternal biological samples during pregnancy and in log-transformed forms. The primary outcome was preterm birth and the secondary outcome was gestational age at birth. Study appraisal, synthesis methods and confidence assessmentQuality of studies was evaluated using OHAT Risk of Bias Tool. Evidence was quantitatively synthesized with Correlated and Hierarchical Effects (CHE) model. The confidence rating in the body of evidence was done using OHAT. ResultsA total of 21 studies reported by 18 papers were included, with 7 studies for preterm birth and 19 for gestational age at birth. The meta-analysis found a ten-fold increase of pesticide concentrations was potentially associated with risk of preterm birth (pooled OR = 1.28; 95%CI: 0.93, 1.78) and shortened gestational age at birth (β = −0.10; 95%CI: −0.21, 0.01). Sampling biospecimens in different trimesters was identified as a potential modifier in the association between pesticide exposure and length of gestational age (F = 2.77, P < 0.05). For studies that collected samples at any time during pregnancy, pesticide exposure was found to be associated with shortened length of gestational age (β = −0.43; 95%CI: −0.81, −0.06). The confidence rating in the body of evidence was “moderate” and “very low” for preterm birth and gestational age at birth, respectively. ConclusionOur result suggested moderate evidence of an association between pesticide exposure and higher risk of preterm birth. Yet more studies are still needed with larger sample size and careful considerations of confounders and accuracy of outcome measurements. Attention is also required on other pesticide compounds in addition to organochlorine and organophosphorus pesticides, and on windows of susceptibility.

Environmental Nickel Exposure and Cardiovascular Disease in a Nationally Representative Sample of U.S. Adults.

Laboratory studies have linked nickel with the pathogenesis of cardiovascular disease (CVD); however, few observational studies in humans have confirmed this association. This study aimed to use urinary nickel concentrations, as a biomarker of environmental nickel exposure, to evaluate the cross-sectional association between nickel exposure and CVD in a nationally representative sample of U.S. adults. Data from a nationally representative sample (n = 2702) in the National Health and Nutrition Examination Survey 2017-20 were used. CVD (n = 326) was defined as self-reported physicians' diagnoses of coronary heart disease, angina, heart attack, or stroke. Urinary nickel concentrations were determined by inductively coupled plasma mass spectrometry. Logistic regression with sample weights was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of CVD. Urinary nickel concentrations were higher in individuals with CVD (weighted median 1.34μg/L) compared to those without CVD (1.08μg/L). After adjustment for demographic, socioeconomic, lifestyle, and other risk factors for CVD, the ORs (95% CIs) for CVD compared with the lowest quartile of urinary nickel were 3.57 (1.73-7.36) for the second quartile, 3.61 (1.83-7.13) for the third quartile, and 2.40 (1.03-5.59) for the fourth quartile. Cubic spline regression revealed a non-monotonic, inverse U-shaped, association between urinary nickel and CVD (Pnonlinearity < 0.001). Nickel exposure is associated with CVD in a non-monotonic manner among U.S. adults independent of well-known CVD risk factors. The online version contains supplementary material available at 10.1007/s12403-023-00579-4.

The design and development of a study protocol to investigate Onchocerca volvulus, Loa loa and Mansonella perstans-mediated modulation of the metabolic and immunological profile in lean and obese individuals in Cameroon.

Life-style metabolic diseases are steadily rising, not only in developed countries, but also in low- and middle-income countries, presenting a global health problem. Metabolic disorders like type 2 diabetes and cardiovascular diseases are among the ten leading causes of death defined by the WHO in 2019. Results from animal and observational human studies suggest a connection between the decline in human helminth infections and rise of life-style-associated metabolic diseases in developing regions. This trial was designed to investigate filarial infections and their impact on metabolic diseases in Cameroon. We hypothesize that the induction of regulatory immune responses during filarial infection reduces obesity-induced low-grade inflammatory immune responses and thereby improves metabolic parameters, whereas anthelmintic treatment abolishes this protective effect. Participants infected with Mansonella perstans, Onchocerca volvulus and/or Loa loa being lean (BMI <25), overweight (BMI >25 and <30) or clinically obese (BMI ≥30) from Littoral regions of Cameroon will be evaluated for their parasitological, immunological, metabolic and biochemical profile before and after treatment of their parasitic infections. Anthropomorphic measurements and a detailed questionnaire will complement our analysis. The investigation will assess blood immune cell populations, serum adipokines and cytokines that could be influenced by the parasite infection and/or metabolic diseases. Further, parameters like blood glucose, homeostatic model assessment of insulin resistance (HOMA-IR), circulating lipids and circulating makers of liver function will be monitored. Parameters will be assessed before treatment, 12 and 18 months after treatment. The focus of this study is to obtain a comprehensive metabolic profile of the participants in rural areas of Cameroon and to investigate the relationship between filarial immunomodulation and metabolic diseases. This study will elucidate the effect of anti-filarial treatment on the metabolic and immunological parameters that partake in the development of insulin resistance, narrowing in on a potential protective effect of filarial infections on metabolic diseases. doi.org/10.1186/ISRCTN43845142, ISRCTN43845142 February 2020 Trial title Effects of filarial parasite infection on type 2 diabetes Issue date: 27.10.22, V.1.

Identifying reproducible resting state networks and functional connectivity alterations following chronic restraint stress in anaesthetized rats.

Resting-state functional MRI (rs-fMRI) in rodent models have the potential to bridge invasive experiments and observational human studies, increasing our understanding of functional alterations in the brains of patients with depression. A major limitation in current rodent rs-fMRI studies is that there has been no consensus on healthy baseline resting-state networks (RSNs) that are reproducible in rodents. Therefore, the present study aimed to construct reproducible RSNs in a large dataset of healthy rats and then evaluate functional connectivity changes within and between these RSNs following a chronic restraint stress (CRS) model within the same animals. A combined MRI dataset of 109 Sprague Dawley rats at baseline and after two weeks of CRS, collected during four separate experiments conducted by our lab in 2019 and 2020, was re-analysed. The mICA and gRAICAR toolbox were first applied to detect optimal and reproducible ICA components and then a hierarchical clustering algorithm (FSLNets) was applied to construct reproducible RSNs. Ridge-regularized partial correlation (FSLNets) was used to evaluate the changes in the direct connection between and within identified networks in the same animals following CRS. Four large-scale networks in anesthetised rats were identified: the DMN-like, spatial attention-limbic, corpus striatum, and autonomic network, which are homologous across species. CRS decreased the anticorrelation between DMN-like and autonomic network. CRS decreased the correlation between amygdala and a functional complex (nucleus accumbens and ventral pallidum) in the right hemisphere within the corpus striatum network. However, a high individual variability in the functional connectivity before and after CRS within RSNs was observed. The functional connectivity changes detected in rodents following CRS differ from reported functional connectivity alterations in patients with depression. A simple interpretation of this difference is that the rodent response to CRS does not reflect the complexity of depression as it is experienced by humans. Nonetheless, the high inter-subject variability of functional connectivity within networks suggests that rats demonstrate different neural phenotypes, like humans. Therefore, future efforts in classifying neural phenotypes in rodents might improve the sensitivity and translational impact of models used to address aetiology and treatment of psychiatric conditions including depression.

Toxicity of Bisphenol in Pregnant Females: First Review of Literature in Humans.

Bisphenol analogues are widely used in consumer products such as disposable dinnerware, canned food, personal care products, bottled beverages, and more, and dietary exposure is the main pathway. Bisphenol A is used to manufacture synthetic resins and commercial plastics in large quantities. According to epidemiological and animal studies, bisphenols disrupt the reproductive, immunological, and metabolic systems. These analogues are estrogenic like Bisphenol A, although human studies are limited. We did a thorough search of the literature on the toxicity of bisphenol on reproductive and endocrine systemsin pregnancy, focusing particularly on human studies. Hence, we present a comprehensive literature review on this topic.​​​​​​​During our literature search,three epidemiological studies and one human observationalstudy demonstrated a substantial link between bisphenol toxicity and recurrent miscarriages.​​​​​​​ The aforementioned research shows that bisphenol may harm pregnancy and cause miscarriages. We believe this is the first literature review on the topic.

Potential antitumor activity of garlic against colorectal cancer: focus on the molecular mechanisms of action.

The aim of this review is to highlight the potential of garlic phytoconstituents as antitumor agents in colorectal cancer management based on their molecular mechanisms of action, while asking if their consumption, as part of the human diet, might contribute to the prevention of colorectal cancer. To gather information on appropriate in vitro, in vivo and human observational studies on this topic, the keywords "Allium sativum", "garlic", "colorectal cancer", "antitumor effect", "in vitro", "in vivo", "garlic consumption" and "colorectal cancer risk" were searched in different combinations in the international databases ScienceDirect, PubMed and Google Scholar. After duplicate and reviews removal, 61 research articles and meta-analyses published between 2000 and 2022 in peer-reviewed journals were found and included in this review. Garlic (Allium sativum) proves to be a rich source of compounds with antitumor potential. Garlic-derived extracts and several of its individual constituents, especially organosulfur compounds such as allicin, diallyl sulfide, diallyl disulfide, diallyl trisulfide, diallyl tetrasulfide, allylmethylsulfide, S-allylmercaptocysteine, Z-ajoene, thiacremonone and Se-methyl-L-selenocysteine were found to possess cytotoxic, cytostatic, antiangiogenic and antimetastatic activities in different in vitro and in vivo models of colorectal cancer. The molecular mechanisms for their antitumor effects are associated with the modulation of several well-known signaling pathways involved in cell cycle progression, especially G1-S and G2-M transitions, as well as both the intrinsic and extrinsic apoptotic pathways. However, even though in various animal models some of these compounds have chemopreventive effects, based on different human observational studies, a diet rich in garlic is not consistently associated with a lower risk of developing colorectal cancer. Independent of the impact of garlic consumption on colorectal cancer initiation and promotion in humans, its constituents might be good candidates for future conventional and/or complementary therapies, based on their diverse mechanisms of action.

An observational human study investigating the effect of anabolic androgenic steroid use on the transcriptome of skeletal muscle and whole blood using RNA-Seq

BackgroundThe effects of Anabolic Androgenic Steroids (AAS) are largely illustrated through Androgen Receptor induced gene transcription, yet RNA-Seq has yet to be conducted on human whole blood and skeletal muscle. Investigating the transcriptional signature of AAS in blood may aid AAS detection and in muscle further understanding of AAS induced hypertrophy.MethodsMales aged 20–42 were recruited and sampled once: sedentary controls (C), resistance trained lifters (RT) and resistance trained current AAS users (RT-AS) who ceased exposure ≤ 2 or ≥ 10 weeks prior to sampling. RT-AS were sampled twice as Returning Participants (RP) if AAS usage ceased for ≥ 18 weeks. RNA was extracted from whole blood and trapezius muscle samples. RNA libraries were sequenced twice, for validation purposes, on the DNBSEQ-G400RS with either standard or CoolMPS PE100 reagents following MGI protocols. Genes were considered differentially expressed with FDR < 0.05 and a 1.2- fold change.ResultsCross-comparison of both standard reagent whole blood (N = 55: C = 7, RT = 20, RT-AS ≤ 2 = 14, RT-AS ≥ 10 = 10, RP = 4; N = 46: C = 6, RT = 17, RT-AS ≤ 2 = 12, RT-AS ≥ 10 = 8, RP = 3) sequencing datasets, showed that no genes or gene sets/pathways were differentially expressed between time points for RP or between group comparisons of RT-AS ≤ 2 vs. C, RT, or RT-AS ≥ 10. Cross-comparison of both muscle (N = 51, C = 5, RT = 17, RT-AS ≤ 2 = 15, RT-AS ≥ 10 = 11, RP = 3) sequencing (one standard & one CoolMPS reagent) datasets, showed one gene, CHRDL1, which has atrophying potential, was upregulated in RP visit two. In both muscle sequencing datasets, nine differentially expressed genes, overlapped with RT-AS ≤ 2 vs. RT and RT-AS ≤ 2 vs. C, but were not differentially expressed with RT vs. C, possibly suggesting they are from acute doping alone. No genes seemed to be differentially expressed in muscle after the long-term cessation of AAS, whereas a previous study found long term proteomic changes.ConclusionA whole blood transcriptional signature of AAS doping was not identified. However, RNA-Seq of muscle has identified numerous differentially expressed genes with known impacts on hypertrophic processes that may further our understanding on AAS induced hypertrophy. Differences in training regimens in participant groupings may have influenced results. Future studies should focus on longitudinal sampling pre, during and post-AAS exposure to better control for confounding variables.

Vitamin D in Diabetes: Uncovering the Sunshine Hormone's Role in Glucose Metabolism and Beyond.

Over the last decades, epidemiology and functional studies have started to reveal a pivotal role of vitamin D in both type 1 and type 2 diabetes pathogenesis. Acting through the vitamin D receptor (VDR), vitamin D regulates insulin secretion in pancreatic islets and insulin sensitivity in multiple peripheral metabolic organs. In vitro studies and both T1D and T2D animal models showed that vitamin D can improve glucose homeostasis by enhancing insulin secretion, reducing inflammation, reducing autoimmunity, preserving beta cell mass, and sensitizing insulin action. Conversely, vitamin D deficiency has been shown relevant in increasing T1D and T2D incidence. While clinical trials testing the hypothesis that vitamin D improves glycemia in T2D have shown conflicting results, subgroup and meta-analyses support the idea that raising serum vitamin D levels may reduce the progression from prediabetes to T2D. In this review, we summarize current knowledge on the molecular mechanisms of vitamin D in insulin secretion, insulin sensitivity, and immunity, as well as the observational and interventional human studies investigating the use of vitamin D as a treatment for diabetes.

The appendix and ulcerative colitis - an unsolved connection.

The appendix is thought to have a role in the pathogenesis of ulcerative colitis, but the nature and basis of this association remains unclear. In this Perspective, we consider the biology of the appendix with respect to its immunological function and the microbiome, and how this relates to evidence that supports the involvement of the appendix in ulcerative colitis. In experimental models, removal of the inflamed appendix prevents colitis, and in human observational studies, appendectomy is associated with protection against ulcerative colitis. Further, among people who develop ulcerative colitis, appendectomy before diagnosis might influence the course and outcomes of the disease - some evidence suggests that it protects against colectomy but could increase the risk of colorectal cancer. Appendectomy after onset of ulcerative colitis seems to have disparate consequences. Clinical trials to understand whether appendectomy has a role in the treatment of ulcerative colitis are ongoing. Major questions about the role of the appendix in the pathogenesis of ulcerative colitis remain unanswered, and further research is needed to establish whether the connection is clinically relevant.

Assessment of Energy and Nutrient Intake and the Intestinal Microbiome (ErNst Study): Protocol and Methods of a Cross-sectional Human Observational Study

On the national level, nutritional monitoring requires the assessment of reliable representative dietary intake data. To achieve this, standardized tools need to be developed, validated, and kept up-to-date with recent developments in food products and the nutritional behavior of the population. Recently, the human intestinal microbiome has been identified as an essential mediator between nutrition and host health. Despite growing interest in this connection, only a few associations between the microbiome, nutrition, and health have been clearly established. Available studies paint an inconsistent picture, partly due to a lack of standardization. First, we aim to verify if food consumption, as well as energy and nutrient intake of the German population, can be recorded validly by means of the dietary recall software GloboDiet, which will be applied in the German National Nutrition Monitoring. Second, we aim to obtain high-quality data using standard methods on the microbiome, combined with dietary intake data and additional fecal sample material, and to also assess the functional activity of the microbiome by measuring microbial metabolites. Healthy female and male participants aged between 18 and 79 years were recruited. Anthropometric measurements included body height and weight, BMI, and bioelectrical impedance analysis. For validation of the GloboDiet software, current food consumption was assessed with a 24-hour recall. Nitrogen and potassium concentrations were measured from 24-hour urine collections to enable comparison with the intake of protein and potassium estimated by the GloboDiet software. Physical activity was measured over at least 24 hours using a wearable accelerometer to validate the estimated energy intake. Stool samples were collected in duplicate for a single time point and used for DNA isolation and subsequent amplification and sequencing of the 16S rRNA gene to determine microbiome composition. For the identification of associations between nutrition and the microbiome, the habitual diet was determined using a food frequency questionnaire covering 30 days. In total, 117 participants met the inclusion criteria. The study population was equally distributed between the sexes and 3 age groups (18-39, 40-59, and 60-79 years). Stool samples accompanying habitual diet data (30-day food frequency questionnaire) are available for 106 participants. Current diet data and 24-hour urine samples for the validation of GloboDiet are available for 109 participants, of which 82 cases also include physical activity data. We completed the recruitment and sample collection of the ErNst study with a high degree of standardization. Samples and data will be used to validate the GloboDiet software for the German National Nutrition Monitoring and to compare microbiome composition and nutritional patterns. German Register of Clinical Studies DRKS00015216; https://drks.de/search/de/trial/DRKS00015216. DERR1-10.2196/42529.

Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs

In 2015, EFSA established a temporary tolerable daily intake (t-TDI) for BPA of 4μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re-evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re-evaluation, a pre-established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57-73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure.

Effect of short-term air pollution exposure on migraine: A protocol for systematic review and meta-analysis on human observational studies

BackgroundThe World Health Organization (WHO) has identified air pollution as one of the greatest environmental risks to public health. High levels of ambient air pollution are known to have adverse health effects, but the relationship between exposure to air pollutants and migraine attack has not been established. ObjectivesThis study aims to systematically review the effects of short-term exposure to fine and coarse particulate matter (PM), ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide on migraine attack. MethodsThe systematic review and meta-analysis will follow the WHO handbook for guideline development. Our protocol will comply with the guidelines of the Preferred Reporting Items for Systematic Review and meta-Analysis Protocols. Eligibility criteriaOriginal peer-reviewed studies conducted in the general population regardless of age and sex to investigate the association between short-term exposure to ambient air pollutants and migraine will be eligible for inclusion. Only time-series, case-crossover, and panel studies will be included. Information sourcesWe will search the electronic databases MEDLINE, Embase, Web of Science, Global Health, Cumulative Index to Nursing and Allied Health Literature in accordance with the pre-established search strategy. We will also check the reference list of included papers and previous reviews for supplementary search. Data synthesis methodWe will perform data extraction in accordance with the predesigned table. Using random-effects meta-analysis, we will present summary statistics (RRs and corresponding 95% CIs) associated with standardized increases in each pollutant level. Heterogeneity between studies will be assessed using 80% prediction intervals (PI). Subgroup analyzes will be performed to explore sources of heterogeneity, if any. The main findings will be presented in summary of finding table, visual display and narrative synthesis. We will review the impact of each air pollutant exposure separately. Evidence appraisalWe will employ the adaption of Grading of Recommendations, Assessment, Development, and Evaluations tool to assess the confidence in the body of evidence.

Maternal Intake of Polyunsaturated Fatty Acids in Autism Spectrum Etiology and Its Relation to the Gut Microbiota: What Do We Know?

Maternal food habits and gut microbiota composition have potential effects on fetal neurodevelopment, impacting Autism Spectrum Disorder (ASD). Our research aims to outline the relationship that ingestion of polyunsaturated fatty acids (PUFAs) and the composition of maternal gut microbiota have with the possible development of ASD in offspring. We suggest that genetic factors could be related to the different conversions between unsaturated fatty acids according to sex and, mainly, the impact of the pregnancy diet on the higher or lower risk of neurological impairments. The proportion of the phyla Firmicutes/Bacteroidetes is high with an increased consumption of linoleic acid (LA, n-6 PUFA), which is associated with maternal intestinal dysbiosis and consequently starts the inflammatory process, harming myelinization. In contrast, the consumption of α-linolenic acid (ALA, n-3 PUFA) tends to re-establish the balance of the maternal microbiota with anti-inflammatory action. Moreover, human observational studies showed a strong correlation between the consumption of n-3 PUFA, mainly above 340 g of fish per week, with beneficial effects on infant neurodevelopment. Therefore, we suggest that the proper intake of foods rich in n-3 PUFAs and their supplementation during pregnancy until lactation has an impact on reducing the development of ASD. Controlled studies with n-3 PUFA supplementation are still necessary to verify the ideal dose and the best form of administration.

Zika Virus from the Perspective of Observational Studies: a Review.

Since 1952 when Zika Virus (ZIKV): a Flavivirus, was first discovered in humans, it has not received enough scientific research compared to some of the other members of the family Flaviviridae; like Dengue Virus (DENV). However, this has not stopped the virus from infecting the human population globally. In particular, the global spread of ZIKV has led to a surge in observational studies. Regarding recently published ZIKV-related literature, we are not aware of any reviews strictly focusing on ZIKV from the perspective of observational studies. Therefore, we reviewed recently published observational studies exploring the global spread of ZIKV and its association with Congenital ZIKV Infection (CZI) and clinical manifestations in adults. Online databases including google scholar, PubMed and Elsevier were used for retrieving relevant studies. ZIKV cases have been reported in different parts of the world, with certain regions reporting more cases than the rest, like Brazil. ZIKV causes a wide spectrum of diseases and disorders including microcephaly, developmental disorders, and Guillain-Barre syndrome to name a few. Furthermore, CZI in neonates mainly manifests into neurological disorders and diseases, whereas ZIKV in adults' targets various organs. ZIKV poses a serious threat to human population and observational studies provide a different perspective on the damaging capabilities of ZIKV in real-life settings. Moreover, there are gaps in the literature regarding ZIKV-related-complications that future experimental studies need to address. These complications include in-utero transmission, Guillain-Barre syndrome, cross-reactivity, sexual transmission, along with its persistence in the male reproductive tract.

Controversies in anesthesia-induced developmental neurotoxicity.

Advances in the field of pediatric anesthesiology have enabled the performance of complex and life-saving procedures with minimal patient discomfort. However, preclinical studies over the past two decades have been reporting substantial neurotoxic potential of general anesthetics in young brain, thus challenging the safety of these agents in pediatric anesthesiology practice. Notwithstanding the overwhelming preclinical evidence, the translatability of these findings has proven inconsistent in human observational studies. The significant degree of anxiety and apprehension surrounding the uncertainty of long-term developmental outcomes following early exposure to anesthesia has prompted numerous studies around the world to investigate the putative mechanisms and translatability of preclinical findings regarding anesthesia-induced developmental neurotoxicity. Guided by the vast preclinical evidence, we aim to highlight relevant human findings presented in the currently available clinical literature.