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Psychiatry Research Jun 2024This study examined the association of clinical factors, independent of sex and high psychosocial adversity (HPAd), with the presence of ADHD or other mental disorders,...
This study examined the association of clinical factors, independent of sex and high psychosocial adversity (HPAd), with the presence of ADHD or other mental disorders, specifically within a middle-income country with a non-Caucasian population. A multi-centric cross-sectional study was conducted in three sites in Colombia. Our study recruited trios of an ADHD proband, one sibling, and one parent. We used valid instruments for assessing parents and siblings. The sample included 223 siblings, an average age of 12.3 (SD 3.9), and 51.1% Females. The ADHD recurrence risk ratio (λ) was 12. The clinical factors mainly associated with the presence of ADHD, independent of sex and HPAd, were 1) Pregnancy and childbirth complications, 2) Delayed psychomotor development, 3) Temperament, and 4) Sleep disturbances. Our research showed that, independently of HPAd and the male sex, there were other clinical factors associated with ADHD and other psychiatric disorders in this population. These findings need to be replicated in similar populations globally.
PubMed: 38941862
DOI: 10.1016/j.psychres.2024.115997 -
Haemophilia : the Official Journal of... Jun 2024Acquired haemophilia A (AHA) is a bleeding disorder caused by autoantibody development against factor VIII (FVIII). Studies on AHA have mainly focused on patients...
INTRODUCTION
Acquired haemophilia A (AHA) is a bleeding disorder caused by autoantibody development against factor VIII (FVIII). Studies on AHA have mainly focused on patients treated at specialist centres.
AIM
To determine the incidence, clinical characteristics and outcomes of AHA in an unselected population-based patient cohort from Finland.
METHODS
This retrospective observational cohort comprised all cases diagnosed with AHA in Finland between 2006 and 2019. Patients were identified by the two central laboratories performing FVIII antibody testing in Finland, the Finnish Red Cross Blood Service and HUSLAB. Clinical details were collected from all hospitals and healthcare units where patients were treated. This study was performed in conjunction with the AHA in the Nordics study.
RESULTS
The median incidence of AHA was 0.65 per million per year (range 0.19-1.27). Fifty-five patients were identified, with a median age of 76 years and an even sex ratio (51% women). When diagnosed, all had bleeding symptoms with severe bleeds in 92%. First-line immunosuppressive treatment regimens included steroid monotherapy in 31% of cases, steroids and a cytotoxic agent in 51% and a rituximab-based regimen in 16%. Clinical remission was achieved in 71% of cases, and 15% had relapses. Mortality was 13% for bleeds and 9% for treatment-related infections. Overall survival was 64% for 1 year and 56% for 2 years after diagnosis.
CONCLUSIONS
In a nationwide population-based cohort study, we discovered a lower incidence of AHA than previously reported. Mortality among patients with AHA was high, calling for the consideration of updated treatment strategies.
PubMed: 38941448
DOI: 10.1111/hae.15037 -
Frontiers in Bioscience (Landmark... May 2024Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence.... (Review)
Review
Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Female; Gastrointestinal Microbiome; Adipose Tissue, Brown; Animals; Insulin Resistance; Fecal Microbiota Transplantation; Obesity
PubMed: 38940030
DOI: 10.31083/j.fbl2906208 -
The Journal of Pharmacology and... Jun 2024Estrogen receptors are essential pharmacological targets for treating hormonal disorders and estrogen-dependent malignancies. Selective activation of estrogen receptor...
Estrogen receptors are essential pharmacological targets for treating hormonal disorders and estrogen-dependent malignancies. Selective activation of estrogen receptor (ER) β is hypothesized to provide therapeutic benefit with reduced risk of unwanted estrogenic side-effects associated with ERα activity. However, activating ERβ without activating α is challenging due to the high sequence and structural homology between the receptor subtypes. We assessed the impact of structural modifications to the parent compound OSU-ERβ-12 on receptor subtype binding selectivity using cell-free binding assays. Functional selectivity was evaluated by transactivation in HEK-293 cells overexpressing human or murine estrogen receptors. selectivity was examined through the uterotrophic effects of the analogs after oral administration in estrogen-naïve female mice. Furthermore, we evaluated the pharmacokinetics of the analogs following single dose IV and oral administration. Regarding selectivity, a single compound exhibited greater functional selectivity than OSU-ERβ-12 for human ERβ. However, like others in the -carborane series, its poor pharmacokinetics limit its suitability for further development. Surprisingly, and at odds with their pharmacokinetic and human activity data, most analogs potently induced uterotrophic effects in estrogen-naïve female mice. Further investigation of activity in HEK293 cells expressing murine estrogen receptors revealed species-specific differences in the ER-subtype selectivity of these analogs. Our findings highlight species-specific receptor pharmacology and the challenges it poses to characterizing developmental therapeutics in preclinical species. This study investigates - and -substituted carborane analogs targeting estrogen receptors, revealing the greater selectivity of carborane analogs for human ERβ compared to the mouse homolog. These findings shed light on the intricacies of using preclinical species in drug development to predict human pharmacology. The report also provides insights for the refinement and optimization of carborane analogs as potential therapeutic agents for estrogen-related disease states.
PubMed: 38936980
DOI: 10.1124/jpet.123.001874 -
Neural Regeneration Research Jun 2024Mature oligodendrocytes form myelin sheaths that are crucial for the Insulation of axons and efficient signal transmission in the central nervous system. Recent evidence...
Mature oligodendrocytes form myelin sheaths that are crucial for the Insulation of axons and efficient signal transmission in the central nervous system. Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons. Despite the recognition of potential heterogeneity in mature oligodendrocyte function, a comprehensive summary of mature oligodendrocyte diversity is lacking. We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes. Indeed, recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences. Furthermore, modern molecular investigations, employing techniques such as single cell/nucleus RNA sequencing, consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region. Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis, Alzheimer's disease, and psychiatric disorders. Nevertheless, caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations. Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity. Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species, sex, central nervous system region, age, and disease, hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
PubMed: 38934385
DOI: 10.4103/NRR.NRR-D-24-00055 -
Molecular Nutrition & Food Research Jun 2024Sex hormone-binding globulin (SHBG) is a homodimeric glycoprotein produced by the human liver and secreted into the systemic circulation where it binds with high... (Review)
Review
Sex hormone-binding globulin (SHBG) is a homodimeric glycoprotein produced by the human liver and secreted into the systemic circulation where it binds with high affinity sex steroids regulating their availability in blood and accessibility to target tissues. Plasma SHBG levels are altered in metabolic disorders such as obesity, anorexia, and insulin resistance. Several reports have shown that diets in terms of total calories or fat, fiber, or protein content can alter plasma SHBG levels. However, there are many components in a diet that can affect SHBG gene expression in the liver. In order to unravel the molecular mechanisms by which diets regulate SHBG production, it would be necessary to analyze single diet components and/or nutritional factors. This review summarizes the recent advances in identifying different nutritional factors regulating SHBG production and the related molecular mechanism, as well as the clinical implications.
PubMed: 38934352
DOI: 10.1002/mnfr.202400020 -
Journal of Diabetes and Metabolic... Jun 2024Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) is an adipokine that is involved in regulation of glucose and lipid metabolism, inflammation, and insulin...
INTRODUCTION
Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) is an adipokine that is involved in regulation of glucose and lipid metabolism, inflammation, and insulin sensitivity. However, the exact role of CTRP6 in metabolic processes remains unclear due to conflicting findings. To address current gap, we aimed to investigate the serum levels of CTRP6 in patients with coronary artery disease (CAD) and its association with inflammatory cytokines.
METHOD
In this case-control study, the serum levels of CTRP6, interlukin-6 (IL-6), tumor necrosis factor- α (TNF-α), adiponectin, and fasting insulin were measured using enzyme-linked immunosorbent assay (ELISA) kits in a total of 176 participants, consisting of 88 CAD patients and 88 control subjects. Additionally, various anthropometric and biochemical measurements were measured and compared between cases and controls.
RESULTS
The present study found that serum levels of CTRP6 were significantly higher in the CAD group (561.3 ± 15.14) compared to the control group (429.3 ± 12.85, < 0.001). After adjusting for age, sex, and body mass index (BMI), CTRP6 levels were found to be positively associated with the risk of CAD ( < 0.001). Correlation analysis in CAD subjects revealed a positive correlation between CTRP6 levels and BMI, systolic blood pressure (SBP), malondialdehyde (MDA), TNF-α, and IL-6, as well as a negative correlation with creatinine and total anti-oxidant capacity.
CONCLUSION
The findings of this study provide novel evidence that elevated serum levels of CTRP6 are significantly associated with an increased risk of developing CAD. Moreover, our results indicate a correlation between CTRP6 and various risk factors for atherosclerosis.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01415-5.
PubMed: 38932850
DOI: 10.1007/s40200-024-01415-5 -
Journal of Diabetes and Metabolic... Jun 2024The Discovery of underlying intermediates associated with the development of dyslipidemia results in a better understanding of pathophysiology of dyslipidemia and their...
PURPOSE
The Discovery of underlying intermediates associated with the development of dyslipidemia results in a better understanding of pathophysiology of dyslipidemia and their modification will be a promising preventive and therapeutic strategy for the management of dyslipidemia.
METHODS
The entire dataset was selected from the Surveillance of Risk Factors of Noncommunicable Diseases (NCDs) in 30 provinces of Iran (STEPs 2016 Country report in Iran) that included 1200 subjects and was stratified into four binary classes with normal and abnormal cases based on their levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and non-HDL-C.Plasma concentrations of 20 amino acids and 30 acylcarnitines in each class of dyslipidemia were evaluated using Tandem mass spectrometry. Then, these attributes, along with baseline characteristics data, were used to check whether machine learning (ML) algorithms could classify cases and controls.
RESULTS
Our ML framework accurately predicts TG binary classes. Among the models tested, the SVM model stood out, performing slightly better with an AUC of 0.81 and a standard deviation of test accuracy at 0.04. Consequently, it was chosen as the optimal model for TG classification. Moreover, the findings showed that alanine, phenylalanine, methionine, C3, C14:2, and C16 had great power in differentiating patients with high TG from normal TG controls. The comprehensive output of this work, along with sex-specific attributes, will improve our understanding of the underlying intermediates involved in dyslipidemia.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01384-9.
PubMed: 38932808
DOI: 10.1007/s40200-024-01384-9 -
Medicina (Kaunas, Lithuania) Jun 2024: Temporomandibular disorders or dysfunction (TMDs) encompass a range of complex conditions that impact the temporomandibular joint (TMJ), chewing muscles, teeth, and/or... (Observational Study)
Observational Study
: Temporomandibular disorders or dysfunction (TMDs) encompass a range of complex conditions that impact the temporomandibular joint (TMJ), chewing muscles, teeth, and/or their supporting tissues. Stress is one of the most associated factors studied as a TMD predictor. The aim is to figure out the influence of stress on TMJ status and salivary cortisol in university students during and before exams. : The study was non-experimental, employing a longitudinal, analytical, observational cohort design. The study population consisted of students enrolled in the physiotherapy degree program at the Alfonso X El Sabio University (Madrid, Spain). Data were collected during two distinct academic periods: the first period was characterized by low academic stress and no exams, and the second period coincided with the high academic stress of final course exams. The collected results included sociodemographic data, assessment of TMJ status (Fonseca Index), evaluation of muscle evaluation (masseter, upper trapezius, and sternocleidomastoid) using a MOXY Monitor (muscle oxygenation) and Neurotrac (surface EMG, sEMG), assessment of perceived stress (PSS-14), and measurement of salivary cortisol (enzyme immunoassay with Elisa). The statistical analysis was conducted with a confidence level of 95% ( ≤ 0.05) and asymptotic or bilateral significance. : 70 students were analyzed during two different measurement periods. According to the Fonseca Index, initially, 37.14% of the analyzed students showed mild TMDs, 17.14% moderate TMDs, and 45.72% showed no TMDs. In general terms, stress increased with age and is related to female sex, maximum mouth opening decreased with age, oxygen saturation decreased with age and academic stress, and myoglobin concentration was related to age. Furthermore, muscle contraction decreased during higher academic stress and increased with age. For women, age was a risk factor for suffering from TMDs, and stress worsened the transition from having TMDs to having no TMDs in both sexes. : Academic stress influences TMJ status and muscle outcomes such as oxygen saturation, myoglobin concentration, and muscle contraction, although more research is needed.
Topics: Humans; Female; Male; Pilot Projects; Stress, Psychological; Temporomandibular Joint Disorders; Temporomandibular Joint; Spain; Adult; Hydrocortisone; Saliva; Young Adult; Longitudinal Studies; Students; Cohort Studies
PubMed: 38929569
DOI: 10.3390/medicina60060952 -
Antioxidants (Basel, Switzerland) Jun 2024Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This... (Review)
Review
Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This paper reviews the literature relevant to the underlying neurobiology of psychosis. The dopamine hypothesis has been a major influence in the study of the neurochemistry of psychosis and in development of antipsychotic drugs. However, it became clear early on that other factors must be involved in the dysfunction involved in psychosis. In the current review, it is reported how several of these factors, namely dysregulation of neurotransmitters [dopamine, serotonin, glutamate, and γ-aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, and oligodendrocytes), the hypothalamic-pituitary-adrenal axis, the gut microbiome, oxidative stress, and mitochondrial dysfunction contribute to psychosis and interact with one another. Research on psychosis has increased knowledge of the complexity of psychotic disorders. Potential new pharmacotherapies, including combinations of drugs (with pre- and probiotics in some cases) affecting several of the factors mentioned above, have been suggested. Similarly, several putative biomarkers, particularly those related to the immune system, have been proposed. Future research on both pharmacotherapy and biomarkers will require better-designed studies conducted on an all stages of psychotic disorders and must consider confounders such as sex differences and comorbidity.
PubMed: 38929148
DOI: 10.3390/antiox13060709