Timely Questions Emerging in Chronobiology: The Circadian Clock Keeps on Ticking.

Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.

Integrating single-cell transcriptomics with cellular phenotypes: cell morphology, Ca2+ imaging and electrophysiology.

I review recent technological advancements in coupling single-cell transcriptomics with cellular phenotypes including morphology, calcium signaling, and electrophysiology. Single-cell RNA sequencing (scRNAseq) has revolutionized cell type classifications by capturing the transcriptional diversity of cells. A new wave of methods to integrate scRNAseq and biophysical measurements is facilitating the linkage of transcriptomic data to cellular function, which provides physiological insight into cellular states. I briefly discuss critical factors of these phenotypical characterizations such as timescales, information content, and analytical tools. Dedicated sections focus on the integration with cell morphology, calcium imaging, and electrophysiology (patch-seq), emphasizing their complementary roles. I discuss their application in elucidating cellular states, refining cell type classifications, and uncovering functional differences in cell subtypes. To illustrate the practical applications and benefits of these methods, I highlight their use in tissues with excitable cell-types such as the brain, pancreatic islets, and the retina. The potential of combining functional phenotyping with spatial transcriptomics for a detailed mapping of cell phenotypes in situ is explored. Finally, I discuss open questions and future perspectives, emphasizing the need for a shift towards broader accessibility through increased throughput.

Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update.

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.

Current and Novel Biologic Therapies for Patients with Asthma and Nasal Polyps.

A substantial portion of asthma and nasal polyps (NPs) share a common pathogenesis, which includes type 2-mediated inflammation. Distinct endotypes and phenotypes characterizing asthma and chronic rhinosinusitis have been identified. With emerging evidence describing pathophysiology, novel targets for biologic monoclonal antibody treatments have been developed. There are currently six biologic therapies approved by the US Food and Drug Administration to treat asthma, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, three of these-omalizumab, mepolizumab, and dupilumab-are also approved for NPs.

Unravelling phenolic metabotypes in the frame of the COMBAT study, a randomized, controlled trial with cranberry supplementation.

Cranberry (poly)phenols may have potential health benefits. Circulating (poly)phenol metabolites can act as mediators of these effects, but they are subjected to an extensive inter-individual variability. This study aimed to quantify both plasma and urine (poly)phenol metabolites following a 12-week intake of a cranberry powder in healthy older adults, and to investigate inter-individual differences by considering the existence of urinary metabotypes related to dietary (poly)phenols. Up to 13 and 67 metabolites were quantified in plasma and urine respectively. Cranberry consumption led to changes in plasma metabolites, mainly hydroxycinnamates and hippuric acid. Individual variability in urinary metabolites was assessed using different data sets and a combination of statistical models. Three phenolic metabotypes were identified, colonic metabolism being the main driver for subject clustering. Metabotypes were characterized by quali-quantitative differences in the excretion of some metabolites such as phenyl-γ-valerolactones, hydroxycinnamic acids, and phenylpropanoic acids. Metabotypes were further confirmed when applying a model only focused on flavan-3-ol colonic metabolites. 5-(3',4'-dihydroxyphenyl)-γ-valerolactone derivatives were the most relevant metabolites for metabotyping. Metabotype allocation was well preserved after 12-week intervention. This metabotyping approach for cranberry metabolites represents an innovative step to handle the complexity of (poly)phenol metabolism in free-living conditions, deciphering the existence of metabotypes derived from the simultaneous consumption of different classes of (poly)phenols. These results will help contribute to studying the health effects of cranberries and other (poly)phenol-rich foods, mainly considering gut microbiota-driven individual differences.

Effects of Vitamin D supplementation or deficiency on metabolic phenotypes in mice of different sexes.

Vitamin D is a steroid hormone precursor that was initially recognized for its important roles in calcium-phosphate homeostasis and bone health. However, the resent prevalence of vitamin D deficiency has highlighted its non-skeletal function, such as its important role in regulating endogenous metabolism. The aim of the present study was to examine the roles of vitamin D supplementation or deficiency on metabolic phenotypes in both male and female mice by using targeted metabolomics analysis. Six weeks old C57BL/6 mice of different sexes were fed with standard chow diet (1000 IU/kg vitamin D3 contained), vitamin D deficient diet (0 IU/kg vitamin D3 contained), or vitamin D enriched diet (10,000 IU/kg vitamin D3 contained) for a total of 14 weeks. Liver pathological analysis showed that vitamin D deficiency caused significant fat deposition in both male and female mice. While vitamin D supplementation was found to improve the accumulation of fat in the liver tissue. Metabolomics analysis indicated that metabolic perturbation related to vitamin D regulation in male mice mainly involved in tricarboxylic acid cycle, fatty acylcarnitine and fatty acid metabolism, sugar metabolism, glutathione metabolism, steroid hormone and pyrimidine metabolism. Based on the criteria of VIP> 1 in OPLS-DA analysis and P < 0.05 in hypothesis test, a total of 62 metabolites and 78 metabolites were found to be significantly changed in VD-deficiency group and VD-supplement group compared with the control group, respectively. While for female mice, the metabolites disturbance mainly involved in fatty acylcarnitine and fatty acid metabolism, TCA, sugar metabolism, folate cycle, methionine cycle, and purine metabolism. A total of 38 and 57 metabolites were found to be significantly changed (VIP>1 and P < 0.05) in VD-deficiency group and VD-supplement group compared with the control group, respectively. Energy metabolism was the most relevant metabolic pathway for vitamin D regulation in both male and female mice. Sex-specific changes of fatty acyl carnitines and dehydroepiandrosterone were observed in the vitamin D supplementation groups. However, most of the energy metabolism related compounds exhibited the same trend in vitamin D supplementation groups of different sexes. Pearson's correlation analysis indicated that vitamin D was significantly correlated (P < 0.05) with the levels of D-fructose 6-phosphate, D-glucose 1-phosphate, D-glucose 6-phosphate, DL-pyroglutamic acid, 2-oxoglutarate, L-glutamic acid, and fumarate, which were all involved in the sugar metabolism pathway. The results achieved in this study demonstrated that vitamin D significantly regulated the metabolism of lipid and sugar, and the regulation showed a certain sex specificity.

Coffee and metabolic phenotypes: A cross-sectional analysis of the Japan multi-institutional collaborative cohort (J-MICC) study.

BACKGROUND AND AIMS: To date, the relationship between coffee consumption and metabolic phenotypes has hardly been investigated and remains controversial. Therefore, the aim of this cross-sectional study is to examine the associations between coffee consumption and metabolic phenotypes in a Japanese population. METHODS AND RESULTS: We analyzed the data of 26,363 subjects (aged 35-69 years) in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. Coffee consumption was assessed using a questionnaire. Metabolic Syndrome (MetS) was defined according to the Joint Interim Statement Criteria of 2009, using body mass index (BMI) instead of waist circumference. Subjects stratified by the presence or absence of obesity (normal weight: BMI <25 kg/m2; obesity: BMI ≥25 kg/m2) were classified by the number of MetS components (metabolically healthy: no components; metabolically unhealthy: one or more components) other than BMI. In multiple logistic regression analyses adjusted for sex, age, and other potential confounders, high coffee consumption (≥3 cups/day) was associated with a lower prevalence of MetS and metabolically unhealthy phenotypes both in normal weight (OR 0.83, 95% CI 0.76-0.90) and obese subjects (OR 0.83, 95% CI 0.69-0.99). Filtered/instant coffee consumption was inversely associated with the prevalence of MetS and metabolically unhealthy phenotypes, whereas canned/bottled/packed coffee consumption was not. CONCLUSION: The present results suggest that high coffee consumption, particularly filtered/instant coffee, is inversely associated with the prevalence of metabolically unhealthy phenotypes in both normal weight and obese Japanese adults.

Yiqi Huayu decoction alleviates bleomycin-induced pulmonary fibrosis in rats by inhibiting senescence.

Overview: In treating pulmonary fibrosis (PF), traditional Chinese medicine (TCM) has received much attention, but its mechanism is unclear. The pharmacological mechanisms of TCM can be explored through network pharmacology. However, due to its virtual screening properties, it still needs to be verified by in vitro or in vivo experiments. Therefore, we investigated the anti-PF mechanism of Yiqi Huayu Decoction (YHD) by combining network pharmacology with in vivo experiments. Methods: Firstly, we used classical bleomycin (BLM)-induced rat model of PF and administrated fibrotic rats with YHD (low-, medium-, and high-dose). We comprehensively assessed the treatment effect of YHD according to body weight, lung coefficient, lung function, and histopathologic examination. Second, we predict the potential targets by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with network pharmacology. In brief, we obtained the chemical ingredients of YHD based on the UHPLC-MS/MS and TCMSP database. We collected drug targets from TCMSP, HERB, and Swiss target prediction databases based on active ingredients. Disease targets were acquired from drug libraries, Genecards, HERB, and TTD databases. The intersecting targets of drugs and disease were screened out. The STRING database can obtain protein-protein interaction (PPI) networks and hub target proteins. Molecular Complex Detection (MCODE) clustering analysis combined with enrichment analysis can explore the possible biological mechanisms of YHD. Enrichment analyses were conducted through the R package and the David database, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome. Then, we further validated the target genes and target proteins predicted by network pharmacology. Protein and gene expression detection by immunohistochemistry, Western blot (WB), and real-time quantitative PCR (rt-qPCR). Results: The results showed that high-dose YHD effectively attenuated BLM-induced lung injury and fibrosis in rats, as evidenced by improved lung function, relief of inflammatory response, and reduced collagen deposition. We screened nine core targets and cellular senescence pathways by UHPLC-MS/MS analysis and network pharmacology. We subsequently validated key targets of cellular senescence signaling pathways. WB and rt-qPCR indicated that high-dose YHD decreased protein and gene expression of senescence-related markers, including p53 (TP53), p21 (CDKN1A), and p16 (CDKN2A). Increased reactive oxygen species (ROS) are upstream triggers of the senescence program. The senescence-associated secretory phenotypes (SASPs), containing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß1 (TGF-ß1), can further exacerbate the progression of senescence. High-dose YHD inhibited ROS production in lung tissue and consistently reduced the SASPs expression in serum. Conclusion: Our study suggests that YHD improves lung pathological injury and lung function in PF rats. This protective effect may be related to the ability of YHD to inhibit cellular senescence.

Sodium butyrate protects against oxidative stress in high-fat-diet-induced obese rats by promoting GSK-3ß/Nrf2 signaling pathway and mitochondrial function.

Sodium butyrate (NaB), obtained by fermenting dietary fiber via intestinal microflora, was recently shown to improve the activity of some antioxidant enzymes in vivo. This study aims to investigate the term changes of mitochondrial energy metabolism and redox homeostasis in skeletal muscles and clarify the regulatory mechanism and dose effect of NaB on skeletal muscle. Male Sprague-Dawley rats were divided into the control group, obesity-prone (OP) group and obesity-resistant (OR) group based on the gain of body weight after 8 weeks' of feeding high-fat diet (HFD), followed by sacrificing rats at the end of 20th week. NaB intervention (12 weeks) could effectively reduce the body weight of rats in the OP and OR groups. NaB also mediated upregulation of antioxidant enzyme activity and GSH/GSSG ratio, while reducing reactive oxygen species (ROS) levels and malondialdehyde (MDA) content. At the molecular level, NaB upregulated Pi3k, Nrf2, Nqo-1, and Ho-1, but downregulated Gsk-3ß mRNA expression by regulating the Nrf2 antioxidant pathway to enhance tissue antioxidant capacity. At the same time, NaB intervention significantly upregulated Glut4, Irs-1, Pdx1, and MafA, expression in gastrocnemius muscles of OP and OR rats, and elevated insulin secretion and muscle insulin sensitivity. Thus, NaB activates antioxidant pathway, improves the antioxidant capacity of obese rat tissues and promotes glucose metabolism. PRACTICAL APPLICATIONS: This study found that obesity-prone and obesity-resistant rats have differences in mitochondrial redox homeostasis and energy metabolism in tissues. Meanwhile, sodium butyrate can effectively promote muscle protein synthesis, increase insulin sensitivity, and promote glucose metabolism in obesity rats. Thus, sodium butyrate supplementation or increasing intestinal butyrate production (e.g., by consuming foods rich in dietary fiber) is a potential means of improving the body's glucose metabolism and obesity profile.

Clinical and behavioral attributes leading to sleep disorders in children on the autism spectrum.

Sleep disorders are a common comorbid condition in children diagnosed with autism spectrum disorder ("autism"). However, the relationship between the clinical features of autism and sleep disorders remains unclear. A better understanding of the inherent autism-related characteristics linked to comorbid sleep disorders would improve comprehensive assessment and management. This study examined the relationship between sociodemographics, autism symptoms, sleep problems, cognitive status, behavioral attributes, and sensory profiles. Using data from 1268 participants who took part in the Australian Autism Biobank, sleep-related measurements using the Child Sleep Habits Questionnaire (CSHQ) were compared between autistic children aged 2 to 17 (N = 969), their siblings (N = 188), and unrelated children without an autism diagnosis (N = 111). The known relationship between sleep problems and autism was further explored by including scores from the Autism Diagnostic Observation Schedule-2, Mullen Scales of Early Learning, Vineland Adaptive Behavioral Scale-II and the Short Sensory Profile-2; which were included in analyses for autistic participants who had a completed CSHQ. Multiple regression models were used to identify clinical/behavioral variables associated with CSHQ subscales. The autism group had a significantly higher total CSHQ score than the sibling and comparison groups (p < 0.001), indicating worse sleep quality. Within the autism group, lower adaptive behaviors (i.e., VABS-II) and sensory issues (i.e., SSP-2 subclass scores) were positively associated with the severity of sleep problems (i.e., the CSHQ subclass scores) (p < 0.001). The significant functional impact of poor sleep on autistic children warrants an assessment of sleep as a critical part of a holistic approach to supporting autistic children and their families. LAY SUMMARY: Autistic children generally have co-occurring conditions. Sleep disorders impact approximately 50%-80% of autistic children. The impact on the quality of life for both the children and their families can be significant. This study compares sleep problems in autistic children and adolescents with their siblings and children without a diagnosis of autism, and investigates the relationship between specific autistic traits, daily life behaviors and sleep problems. The findings highlight the importance of a holistic assessment for autistic children and matching appropriate sleep intervention and supports where indicated.

Treatment options in obstructive sleep apnea.

Treatment of OSA with CPAP is currently the recommended treatment and has the greatest evidence of efficacy on AHI, symptoms and comorbidities. Symptomatic patients with moderate-severe OSA generally have good adherence to CPAP therapy, while those with mild OSA, female, young and generally paucisymptomatic, have lower CPAP adherence, especially in the medium and long term. The recent identification of different clinical and pathophysiological phenotypes of OSA has paved the way for alternative treatments to CPAP, leading to an increasingly personalized therapy. Weight loss and lifestyle modifications are highly recommended in all obese or overweight patients. Mandibular advancement devices (MAD), positional therapy (PT) and hypoglossal nerve stimulation (HSN) are recent and personalized alternative therapies on which there is promising and encouraging data but with still little strong scientific evidence. The purpose of this review is to compare the efficacy, adherence and costs of various therapeutic options for OSA patients in the light of recent evidence and to provide useful guidance for specialists.

Cardiovascular risks and sociodemographic correlates of multidimensional sleep phenotypes in two samples of US adults.

Study Objectives: Sleep is a modifiable risk factor for cardiovascular conditions. Holistic examination of within-person, multidimensional sleep patterns may offer more detailed information about the sleep-cardiovascular condition link, including who is more vulnerable to both. This study aimed to identify common sleep phenotypes in adulthood, establish the validity of the phenotypes in relation to cardiovascular conditions, and explore sociodemographic and background characteristics of the phenotypes. Methods: Across two independent samples of adults (N 1 = 4600; N 2 = 2598) from the Midlife in the United States Study, latent class analysis (LCA) extracted sleep phenotypes using five key self-reported sleep dimensions. Log-binomial regression was used to determine whether sleep phenotypes differentially predicted cardiovascular conditions, adjusting for known risk factors. LCA with covariates was used to compare sociodemographic characteristics of the identified sleep phenotypes. Results: Four sleep phenotypes were identified consistently across the two samples: good sleepers, nappers, dissatisfied/inefficient sleepers, and irregular sleepers. Compared to good sleepers (reference), dissatisfied/inefficient sleepers exhibited a higher risk of cardiovascular conditions in both samples (RR Sample1: 29%, RR Sample2: 53%) and consisted of relatively more racial/ethnic minorities. Nappers exhibited a higher risk of cardiovascular conditions in one sample (RR Sample1: 38%) and consisted of more women and older adults. Irregular sleepers exhibited no significantly different cardiovascular risk and were relatively younger. Conclusions: Common sleep phenotypes in adulthood exhibit differential risks for cardiovascular conditions. Cooccurring sleep dissatisfaction and inefficiency, in particular, may relate to increased risk of cardiovascular conditions. Certain sociodemographic groups (racial minorities, women, older adults) disproportionately fit within high-risk sleep phenotypes.

Glial-Neuronal Interactions in Pathogenesis and Treatment of Spinal Cord Injury.

Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macrophages and microglia, which triggers activation of genes responsible for the dysregulated microenvironment within the lesion site and in the spinal cord parenchyma immediately adjacent to the lesion. Recently published data indicate that microglia induces astrocyte activation and determines the fate of astrocytes. Conversely, astrocytes have the potency to trigger microglial activation and control their cellular functions. Here we review current information about the release of diverse signaling molecules (pro-inflammatory vs. anti-inflammatory) in individual cell phenotypes (microglia, astrocytes, blood inflammatory cells) in acute and subacute SCI stages, and how they contribute to delayed neuronal death in the surrounding spinal cord tissue which is spared and functional but reactive. In addition, temporal correlation in progressive degeneration of neurons and astrocytes and their functional interactions after SCI are discussed. Finally, the review highlights the time-dependent transformation of reactive microglia and astrocytes into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide suggestions on how to modulate the inflammation and discuss key therapeutic approaches leading to better functional outcome after SCI.

Identification of NSP3 (SH2D3C) as a Prognostic Biomarker of Tumor Progression and Immune Evasion for Lung Cancer and Evaluation of Organosulfur Compounds from Allium sativum L. as Therapeutic Candidates.

The multi-domain non-structural protein 3 (NSP3) is an oncogenic molecule that has been concomitantly implicated in the progression of coronavirus infection. However, its oncological role in lung cancer and whether it plays a role in modulating the tumor immune microenvironment is not properly understood. In the present in silico study, we demonstrated that NSP3 (SH2D3C) is associated with advanced stage and poor prognoses of lung cancer cohorts. Genetic alterations of NSP3 (SH2D3C) co-occurred inversely with Epidermal Growth Factor Receptor (EGFR) alterations and elicited its pathological role via modulation of various components of the immune and inflammatory pathways in lung cancer. Our correlation analysis suggested that NSP3 (SH2D3C) promotes tumor immune evasion via dysfunctional T-cell phenotypes and T-cell exclusion mechanisms in lung cancer patients. NSP3 (SH2D3C) demonstrated a high predictive value and association with therapy resistance in lung cancer, hence serving as an attractive target for therapy exploration. We evaluated the in silico drug-likeness and NSP3 (SH2D3C) target efficacy of six organosulfur small molecules from Allium sativum using a molecular docking study. We found that the six organosulfur compounds demonstrated selective cytotoxic potential against cancer cell lines and good predictions for ADMET properties, drug-likeness, and safety profile. E-ajoene, alliin, diallyl sulfide, 2-vinyl-4H-1,3-dithiin, allicin, and S-allyl-cysteine docked well into the NSP3 (SH2D3C)-binding cavity with binding affinities ranging from -4.3~-6.70 A and random forest (RF) scores ranging from 4.31~5.26 pKd. However, S-allyl-cysteine interaction with NSP3 (SH2D3C) is unfavorable and hence less susceptible to NSP3 ligandability. In conclusion, our study revealed that NSP3 is an important onco-immunological biomarker encompassing the tumor microenvironment, disease staging and prognosis in lung cancer and could serve as an attractive target for cancer therapy. The organosulfur compounds from A. sativum have molecular properties to efficiently interact with the binding site of NSP3 and are currently under vigorous preclinical study in our laboratory.

Correlations between Coffee Consumption and Metabolic Phenotypes, Plasma Folate, and Vitamin B12: NHANES 2003 to 2006.

Metabolic syndrome (MetS) is prevalent not only among the overweight and obese but also normal weight individuals, and the phenotype is referred to as a metabolically unhealthy phenotype (MUHP). Besides normal weight individuals, overweight/obese individuals are also protected from MetS, and the phenotype is known as a metabolically healthy phenotype (MHP). Epidemiological studies indicate that coffee and micronutrients such as plasma folate or vitamin B12 (vit. B12) are inversely associated with MetS. However, correlations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 remain unknown. Our objective was to investigate the correlation between coffee consumption, metabolic phenotypes, plasma folate, and vit. B12 as well as to understand associations between plasma folate, vit. B12, and metabolic phenotypes. Associations among coffee consumption metabolic phenotypes, plasma folate, and vit. B12 were assessed in a cross-sectional study of 2201 participants, 18 years or older, from 2003-2004 and 2005-2006 National Health and Nutrition Examination Surveys (NHANES). MUHP was classified as having > three metabolic abnormalities. Coffee consumption was not associated with metabolic phenotypes, but negatively correlated with several metabolic variables, including BMI (p < 0.001). Plasma folate was positively associated with MUHP (p < 0.004), while vit. B12 was inversely associated with MUHP (p < 0.035). Our results suggest the potential protective impact of coffee on individual components of MetS and indicate a positive correlation between coffee consumption and MUHP among overweight individuals. Identifying possible dietary factors may provide practical and low-cost dietary intervention targets, specifically for early intervention. Larger and randomized intervention studies and prospective longitudinal studies are required to further evaluate these associations.

Comparing dysmenorrhea beliefs and self-management techniques across symptom-based phenotypes.

OBJECTIVES: To compare beliefs about dysmenorrhea and self-management techniques across three dysmenorrhea symptom-based phenotypes. BACKGROUND: Many reproductive-age women experience dysmenorrhea, with varying symptoms and intensity. Dysmenorrhea symptom-based phenotypes have been identified in previous research, defining distinctive phenotypes of mild localised pain, severe localised pain, and multiple severe symptoms. It is unknown if women from different phenotypes hold different beliefs about dysmenorrhea or if they engage in different self-management techniques. DESIGN: Quantitative secondary analysis of cross-sectional survey data. METHODS: This online study surveyed 762 women with dysmenorrhea in the United States. Participants reported their dysmenorrhea symptom intensity, beliefs about dysmenorrhea (i.e. beliefs about consequences, timeline, controllability, symptom severity, normalcy, emotional response to symptoms and treatments) and self-management techniques to prevent or treat symptoms. Beliefs regarding dysmenorrhea and types of self-management techniques used were compared across three phenotypes utilising ANOVA tests and Tukey's HSD for pairwise comparisons. Reporting followed the STROBE guidelines. RESULTS: Women with multiple severe symptoms had significantly more negative beliefs regarding dysmenorrhea and utilised significantly more self-management techniques than women with severe localised pain and women with mild localised pain. Women with severe localised pain had significantly more negative beliefs regarding dysmenorrhea and utilised significantly more self-management techniques than women with mild localised pain. Negative beliefs regarding dysmenorrhea included: consequences of dysmenorrhea, timeline of symptoms, personal and treatment control, symptom severity, normalcy of symptoms, emotional response to symptoms and willingness to utilise complementary medicine. CONCLUSION: Results further support the distinction between dysmenorrhea symptom-based phenotypes. Not only do women in different phenotypes experience different severity and number of dysmenorrhea symptoms, they also perceive and manage their dysmenorrhea differently. RELEVANCE TO CLINICAL PRACTICE: These findings have implications for tailoring interventions to different dysmenorrhea symptom-based phenotypes.

An integrative toxicogenomic analysis of plastic additives.

In developed countries, contact with plastics is constant. Plastics contain a vast number of additives such as plasticisers, stabilisers, antioxidants, flame retardants, etc., that can impact human health. Most of them have been studied separately; however, an integrative approach to identify genes, biological processes, molecular functions, and diseases linked to exposure to these compounds has not been addressed until now. The genes most commonly affected by plastic additives are related to apoptosis, cell death, proliferation and differentiation, immunity and insulin-related processes, and are mainly associated with cancer, mental disorders, diabetes mellitus type II and obesity. The most commonly affected molecular functions included steroid hormone receptor activity implicated in cancer, mental disorders, immune signalling and gonadotropin-releasing hormones. These processes and functions affected by plastic additives are related to the diseases of the developed world, most of which are linked to the endocrine system, such as cancer, diabetes, infertility and obesity. The strong interconnection among the top 50 genes modulated by plastic additives shows that the pathways affected are strongly interrelated. Therefore, studying the effects of plastic additives through a single-compound approach cannot be sufficient and a holistic approach is more appropriate for evaluating the potential effects of plastics in human health.

Tailoring treatment for PCOS phenotypes.

Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive-aged women. Hyperandrogenism, polycystic ovaries, chronic anovulation, and metabolic aberrations are its common features. The treatment approach focuses on the main aberrations, which characterize the different phenotypes. Areas covered: Management strategies targeting the metabolic phenotype include lifestyle modifications for weight loss and improvement of dietary habits, as well as medication, such as insulin-sensitizers. The treatment of hyperandrogenic phenotype includes cosmetic procedures and the combined oral contraceptives with or without antiandrogens. The therapeutic approach to reproductive phenotype includes diet and lifestyle modifications, clomiphene citrate, and aromatase inhibitors. Alternative treatments include dietary supplements, herbs, resveratrol, myo-inositol, and acupuncture. Expert opinion: New studies have shown that higher anti-Müllerian hormone levels, gut microbiome composition, and plasma metabolomics are new parameters that are related to the most severe phenotypes. The clinical phenotypes can change over the lifespan with weight gain and can coexist in the same individual. Individualized treatment remains the main approach but grouping the phenotypes and following therapeutic recommendations may prove to be also clinically appropriate.

Effects of slow- v. fast-digested protein supplementation combined with mixed power training on muscle function and functional capacities in older men.

Ageing leads to a progressive loss of muscle function (MF) and quality (MQ: muscle strength (MS)/lean muscle mass (LM)). Power training and protein (PROT) supplementation have been proposed as efficient interventions to improve MF and MQ. Discrepancies between results appear to be mainly related to the type and/or dose of proteins used. The present study aimed at determining whether or not mixed power training (MPT) combined with fast-digested PROT (F-PROT) leads to greater improvements in MF and MQ in elderly men than MPT combined with slow-digested PROT (S-PROT) or MPT alone. Sixty elderly men (age 69 (sd 7) years; BMI 18-30 kg/m2) were randomised into three groups: (1) placebo + MPT (PLA; n 19); (2) F-PROT + MPT (n 21) and (3) S-PROT + MPT (n 20) completed the intervention. LM, handgrip and knee extensor MS and MQ, functional capacity, serum metabolic markers, skeletal muscle characteristics, dietary intake and total energy expenditure were measured. The interventions consisted in 12 weeks of MPT (3 times/week; 1 h/session) combined with a supplement (30 g:10 g per meal) of F-PROT (whey) or S-PROT (casein) or a placebo. No difference was observed among groups for age, BMI, number of steps and dietary intake pre- and post-intervention. All groups improved significantly their LM, lower limb MS/MQ, functional capacity, muscle characteristics and serum parameters following the MPT. Importantly, no difference between groups was observed following the MPT. Altogether, adding 30 g PROT/d to MPT, regardless of the type, does not provide additional benefits to MPT alone in older men ingesting an adequate (i.e. above RDA) amount of protein per d.