Role In Etiology Research Articles

Gene-environment interactions between clonal hematopoiesis of indeterminate potential and air pollution in non-small cell lung cancer among non-smokers.

10514 Background: Small particulate matter air pollution (≤ 2.5µm diameter; PM2.5) is a recognized driver of non-small cell lung cancer (NSCLC) among non-smokers. PM2.5 recruits pro-inflammatory macrophages to the lungs, which facilitate the clonal expansion of mutated epithelial cells and eventual transformation to NSCLC. Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related condition caused by the acquisition of somatic mutations in hematopoietic stem cells. CHIP and its accompanying pro-inflammatory phenotype have been linked with various age-related diseases, including incident NSCLC; however, the mechanisms underlying this relationship are unknown. In this study, we aimed to explore the interaction between CHIP and exposure to PM2.5 in the development of incident NSCLC. Methods: This study was conducted using data from participants in the UK Biobank (n = 451,095). CHIP status was determined from peripheral blood whole exome sequencing data, and defined as the presence of a somatic driver mutation in the blood at variant allele frequency (VAF) ≥2% (PMID: 36652671). Incident NSCLC was determined from UK cancer registry data, and PM2.5 exposure was determined based on ambient regional measures from 2010. Cox proportional hazard models were used to evaluate associations between CHIP, PM2.5, and NSCLC. Proteomics data was measured using OLINK proteomics in a subset of UK Biobank participants (n = 44,625). Results: CHIP was prevalent in 3.4% of UK Biobank participants (n = 15,633; never smokers: 3.0%, n = 6,916/227,133). There were 1983 incident cases of NSCLC (never smokers: n = 307). CHIP status was associated with incident NSCLC when adjusting for smoking status (HR = 1.73, 95% CI: 1.48–2.02) and analyzing exclusively non-smokers (HR = 2.01, 95% CI: 1.34-3.00). PM2.5 levels were not associated with NSCLC in non-smokers (HR = 1.00, 95% CI: 0.89–1.12 per µg/m3 increase in PM2.5); however, there was a significant interaction between PM2.5 and CHIP (HR = 1.46, 95% CI: 1.02–2.11, pint = 0.04), suggesting that it is the interplay between the two that drives incident NSCLC risk. We found no association between PM2.5 levels and increased CHIP prevalence or CHIP VAF. PM2.5 and CHIP were also found to interact to increase systemic inflammatory markers C-reactive peptide (pint = 0.01) and IL-6 (pint = 0.002). Conclusions: PM2.5 and CHIP act as a novel gene x environment interaction pair that play a key role in NSCLC etiology among non-smokers. Rather than acting in isolation to increase risk of NSCLC, PM2.5 intensifies the relationship between CHIP and NSCLC, presumably by exacerbating systemic inflammation and the hyper-inflammatory lung microenvironment. With PM2.5 levels in the UK among the lowest in the world, we posit that the CHIP x PM2.5 interaction contributes substantially to the global burden of NSCLC in non-smokers.

185P The combined role of patients (pts) gender and disease etiology on unresectable HCC (uHCC) first-line (1L) treatment outcome

185P The combined role of patients (pts) gender and disease etiology on unresectable HCC (uHCC) first-line (1L) treatment outcome

Reported Personality Traits and Histories of Childhood Maltreatment in Borderline Personality Disorder and Bipolar 2 Disorder: A Comparative Study

This study compared borderline personality disorder (BPD) and bipolar 2 disorder (BP 2 disorder) with respect to reported childhood trauma and Five-Factor personality traits using the Childhood Trauma Questionnaire (CTQ) and the NEO Five-Factor Inventory (NEO-FFI). Participants were 50 men and women, aged 18-45, with DSM-5-diagnosed BPD and 50 men and women in the same age group with DSM-5-diagnosed BP 2 disorder. Participants could not meet criteria for both BPD and BP 2 disorder. Borderline participants had significantly higher scores on the neuroticism subscale and significantly lower scores on the agreeableness subscale of the NEO-FFI. After correction for multiple comparisons, there were no between-group differences on CTQ scores. Study results suggest that BPD and BP 2 disorder differ primarily with respect to underlying temperament/genetic architecture and that environmental factors have only a limited role in the differential etiologies of the two disorders.

The Contribution of Mosaic Chromosomal Alterations to Schizophrenia

BackgroundMosaic chromosomal alterations are implicated in neuropsychiatric disorders, but the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages has not been fully established. MethodsWe analyzed blood-derived genotype arrays from 9715 patients with SCZ and 28,822 control participants of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mosaic chromosomal alterations. We focused on probable early developmental sCNVs through stringent filtering. We assessed the burden of sCNVs across varying cell fraction cutoffs, as well as the frequency with which genes were involved in sCNVs. We integrated this data with the PGC (Psychiatric Genomics Consortium) dataset, which comprises 12,834 SCZ cases and 11,648 controls of European descent, and complemented it with genotyping data from postmortem brain tissue of 936 participants (449 cases and 487 controls). ResultsPatients with SCZ had a significantly higher somatic losses detection rate than control participants (1.00% vs. 0.52%; odds ratio = 1.91; 95% CI, 1.47–2.49; two-sided Fisher’s exact test, p = 1.49 × 10−6). Further analysis indicated that the odds ratios escalated proportionately (from 1.91 to 2.78) with the increment in cell fraction cutoffs. Recurrent sCNVs associated with SCZ (odds ratio > 8; Fisher’s exact test, p < .05) were identified, including notable regions at 10q21.1 (ZWINT), 3q26.1 (SLITRK3), 1q31.1 (BRINP3) and 12q21.31-21.32 (MGAT4C and NTS) in the Chinese cohort, and some regions were validated with PGC data. Cross-tissue validation pinpointed somatic losses at loci like 1p35.3-35.2 and 19p13.3-13.2. ConclusionsThe study highlights the significant impact of mosaic chromosomal alterations on SCZ, suggesting their pivotal role in the disorder’s genetic etiology.

THE ROLE OF AEROBIC AND ANAEROBIC MICROFLORA IN THE DEVELOPMENT OF DENTAL MUCOSITIS AND DENTAL PERI-IMPLANTITIS

In modern conditions, mixed oral infections: pathogenic and opportunistic bacteria, fungi and protozoa are becoming increasingly important in the emergence of delayed inflammatory complications after dental implantation. Literature data shows that violations of normobiosis in all mucous membranes of the oral cavity are associated with its hygienic condition, dental and periodontal diseases. Local immune protection factors are not of minor importance. To date, the etiological role of the entire group of microorganisms in the appearance of dental mucosa and tooth fairy-implantitis has not been determined. We are talking, first of all, about fungi of the genus Candida, streptococci and staphylococci, the presence of which in the tissues of the oral cavity often indicates immunological diseases in the body, as well as anaerobes found without periodontal signs. tissue disease [2]. In this regard, under certain and not yet fully understood conditions, special attention should be paid to these infectious factors that can lead to the development of inflammatory and inflammatory-destructive complications after surgical interventions carried out to install implants. Rational and effective diagnosis of microbial infection in patients with inflammatory complications after dental implantation remains an unresolved problem, no highly effective pathogenetic methods of its elimination have been developed.

Is autism a PIN1 deficiency syndrome? A proposed etiological role for glyphosate.

Autism is a neurodevelopmental disorder, the prevalence of which has increased dramatically in the United States over the past two decades. It is characterized by stereotyped behaviors and impairments in social interaction and communication. In this paper, we present evidence that autism can be viewed as a PIN1 deficiency syndrome. Peptidyl-prolyl cis/trans isomerase, NIMA-Interacting 1 (PIN1) is a peptidyl-prolyl cis/trans isomerase, and it has widespread influences in biological organisms. Broadly speaking, PIN1 deficiency is linked to many neurodegenerative diseases, whereas PIN1 over-expression is linked to cancer. Death-associated protein kinase 1 (DAPK1) strongly inhibits PIN1, and the hormone melatonin inhibits DAPK1. Melatonin deficiency is strongly linked to autism. It has recently been shown that glyphosate exposure to rats inhibits melatonin synthesis as a result of increased glutamate release from glial cells and increased expression of metabotropic glutamate receptors. Glyphosate's inhibition of melatonin leads to a reduction in PIN1 availability in neurons. In this paper, we show that PIN1 deficiency can explain many of the unique morphological features of autism, including increased dendritic spine density, missing or thin corpus callosum, and reduced bone density. We show how PIN1 deficiency disrupts the functioning of powerful high-level signaling molecules, such as nuclear factor erythroid 2-related factor 2 (NRF2) and p53. Dysregulation of both of these proteins has been linked to autism. Severe depletion of glutathione in the brain resulting from chronic exposure to oxidative stressors and extracellular glutamate leads to oxidation of the cysteine residue in PIN1, inactivating the protein and further contributing to PIN1 deficiency. Impaired autophagy leads to increased sensitivity of neurons to ferroptosis. It is imperative that further research be conducted to experimentally validate whether the mechanisms described here take place in response to chronic glyphosate exposure and whether this ultimately leads to autism.

Does Positioning During Oral and Maxillofacial Surgery Operations Influence the Development of Upper Extremity Peripheral Neuropathy?

BackgroundControversy exists regarding the role of specific etiology and mitigating factors in perioperative upper extremity peripheral neuropathy (PUN) development during oral and maxillofacial surgery (OMS) procedures. PurposeThe purpose of this study was to measure the association between upper extremity positioning and developing PUN in oral and maxillofacial surgery operations. Study design, setting, sampleThe investigators implemented a retrospective cohort study. Patients referred to the Department of Oral and Maxillofacial Surgery at Jefferson Health who underwent orthognathic, telegnathic, or free flap surgery from April 2017 through December 2021 were identified. Exclusion criteria were age less than 13, revision surgery, ablative case without free flap reconstruction, incomplete medical record, pre-existing neuropathy, and upper extremity position other than tucked or abducted. Predictor variableThe predictor variable was upper extremity (UE) position during surgery, which had two levels-- tucked or abducted. Outcome variableThe outcome variable was self-reported development of PUN, defined as new sensory and/ or motor deficit in a non-operated extremity diagnosed within 48 hours of surgery. CovariatesDemographic covariates included age, gender, and race. Perioperative covariates included American Society of Anesthesiologists (ASA) physical status and body mass index (BMI). The operative covariate was general anesthesia (GA) duration. AnalysesDescriptive statistics were calculated. Shapiro-Wilk test was used to assess normality of the sample. Categorical variables were analyzed with Fisher’s exact test. Continuous variables were analyzed with Mann-Whitney U test. Significance was defined at P<0.05. ResultsOf the 432 patients identified, 342 met inclusion criteria. Median (IQR) ages for the abducted and tucked cohorts were 40 (31) and 34 (28) years, respectively (P<0.01). Males comprised 55.4% (n=41) and 54.1% (n=145) of abducted and tucked groups, respectively (P=0.9). PUN frequency was 6.8% (n=5) for abducted subjects and 3.7% (n=10) for tucked subjects (relative risk 1.8, 95%CI [0.7,5.1]; P=0.33). PUN was associated with gender (P=0.01), ASA status (P=0.03), BMI (P=0.01), and GA duration (P<0.01) on bivariate analysis. When adjusting for covariates, only GA duration (P<0.01) and BMI (P=0.03) were associated with PUN development Conclusion and relevanceThe findings suggest that PUN development during OMS procedures was not associated with upper extremity position.

Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions.

Human endogenous retroviruses (HERVs) are repetitive elements previously implicated in major psychiatric conditions, but their role in aetiology remains unclear. Here, we perform specialised transcriptome-wide association studies that consider HERV expression quantified to precise genomic locations, using RNA sequencing and genetic data from 792 post-mortem brain samples. In Europeans, we identify 1238 HERVs with expression regulated in cis, of which 26 represent expression signals associated with psychiatric disorders, with ten being conditionally independent from neighbouring expression signals. Of these, five are additionally significant in fine-mapping analyses and thus are considered high confidence risk HERVs. These include two HERV expression signatures specific to schizophrenia risk, one shared between schizophrenia and bipolar disorder, and one specific to major depressive disorder. No robust signatures are identified for autism spectrum conditions or attention deficit hyperactivity disorder in Europeans, or for any psychiatric trait in other ancestries, although this is likely a result of relatively limited statistical power. Ultimately, our study highlights extensive HERV expression and regulation in the adult cortex, including in association with psychiatric disorder risk, therefore providing a rationale for exploring neurological HERV expression in complex neuropsychiatric traits.

ПРОБЛЕМА ОЖИРЕНИЯ У ДЕТЕЙ И ПОДРОСТКОВ

Currently, the problem of obesity and overweight in children and adolescents is a serious public threat, the prevalence of which continues to grow rapidly in many countries around the world. The occurrence of obesity depends on a combination of various and dangerous etiological factors. Obesity and overweight have many pathogenetic links that cause adverse and dangerous health effects, significantly impair the quality of life and reducing its duration. High prevalence, life-threatening consequences, unsuccessful therapy, large financial costs and social discrimination put obesity and overweight in a special place among modern problems of medicine and healthcare. This study is devoted to the study of etiology, pathogenesis and influence of overweight on human health, evaluating the outcomes in clinical studies of obesity in children and adolescents. The study of the problem of obesity in children and adolescents should be aimed at identifying the relationship between various components of pathogenesis and the development of adverse consequences of obesity, taking into account the role of etiology – genetic and environmental factors. It is necessary to systematically approach the treatment of obesity and its complications, taking into account the multifactorial etiology and pathogenesis of this condition. Such tactics will help to find potential targets for obesity therapy, individual approaches in the diagnosis, treatment and prevention of this disease, which is crucial in the fight against this global epidemic.

Studying the context of psychoses to improve outcomes in Ethiopia (SCOPE): Protocol paper

Background Global evidence on psychosis is dominated by studies conducted in Western, high-income countries. The objectives of the Study of Context Of Psychoses to improve outcomes in Ethiopia (SCOPE) are (1) to generate rigorous evidence of psychosis experience, epidemiology and impacts in Ethiopia that will illuminate aetiological understanding and (2) inform development and testing of interventions for earlier identification and improved first contact care that are scalable, inclusive of difficult-to-reach populations and optimise recovery. Methods The setting is sub-cities of Addis Ababa and rural districts in south-central Ethiopia covering 1.1 million people and including rural, urban and homeless populations. SCOPE comprises (1) formative work to understand care pathways and community resources (resource mapping); examine family context and communication (ethnography); develop valid measures of family communication and personal recovery; and establish platforms for community engagement and involvement of people with lived experience; (2a) a population-based incidence study, (2b) a case-control study and (2c) a cohort study with 12 months follow-up involving 440 people with psychosis (390 rural/Addis Ababa; 50 who are homeless), 390 relatives and 390 controls. We will test hypotheses about incidence rates in rural vs. urban populations and men vs. women; potential aetiological role of khat (a commonly chewed plant with amphetamine-like properties) and traumatic exposures in psychosis; determine profiles of needs at first contact and predictors of outcome; (3) participatory workshops to develop programme theory and inform co-development of interventions, and (4) evaluation of the impact of early identification strategies on engagement with care (interrupted time series study). Findings will inform development of (5) a protocol for (5a) a feasibility cluster randomised controlled trial of interventions for people with recent-onset psychosis in rural settings and (5b) two uncontrolled pilot studies to test acceptability, feasibility of co-developed interventions in urban and homeless populations.

MICROFLORA OF THE UROGENITAL TRACT IN ACUTE PURULENTINFLAMMATORY DISEASES OF THE URINARY SYSTEM AS A PREREQUISITE OF ABDOMINAL SEPSIS

The aim – to ascertain the etiological role of various taxonomic groups of autochthonousand allochthonous microorganisms in the origin of acute purulent- inflammatory diseasesof the urinary system as a prerequisite of abdominal sepsis.Materials and methods. The study covers 145 patients with acute purulent- inflammatorydiseases of the urinary system. When studying the microbiota of the urinary system,standard microbiological methods were used, the number of colony- forming units(CFU) was counted, determining the population level of each species or group of themicroorganisms, the obtained numerical values were converted into a decimal logarithm(lg CFU). The etiopathogenetic value of individual representatives of the microbiotawas assessed by the constancy index, frequency and significance indicators, as well asthe coefficient of quantitative dominance of each type of microorganisms, and otherindicators (Margalef index, Berger- Parker dominance index).Results. Acute purulent- inflammatory diseases of the urinary system are polyetiologicaldiseases caused by microorganisms belonging to different taxonomic groups. The leadingrole belongs to opportunistic Escherichia, to a lesser extent enteropathogenic E.coli,as well as conditionally pathogenic Staphylococci, in addition to that only in a small(13.48 %) number of patients it was not possible to isolate and identify the pathogens.Associations of pathogens were often encountered, which testifies to the need of developingan antimicrobial effect on etiological factors. Conclusions. Acute purulent- inflammatory diseases of the urinary system arecharacterized by polyetiological factors, a variety of pathogens with the dominant roleof Escherichia coli and Staphylococci. The identified pathogens create the potentialfor translocation and formation, under certain conditions, of abdominal sepsis in thiscontingent of patients.

A new perspective on therapies involving B-cell depletion in autoimmune diseases.

It has been rediscovered in the last fifteen years that B-cells play an active role in autoimmune etiology rather than just being spectators. The clinical success of B-cell depletion therapies (BCDTs) has contributed to this. BCDTs, including those that target CD20, CD19, and BAFF, were first developed to eradicate malignant B-cells. These days, they treat autoimmune conditions like multiple sclerosis and systemic lupus erythematosus. Particular surprises have resulted from the use of BCDTs in autoimmune diseases. For example, even in cases where BCDT is used to treat the condition, its effects on antibody-secreting plasma cells and antibody levels are restricted, even though these cells are regarded to play a detrimental pathogenic role in autoimmune diseases. In this Review, we provide an update on our knowledge of the biology of B-cells, examine the outcomes of clinical studies employing BCDT for autoimmune reasons, talk about potential explanations for the drug's mode of action, and make predictions about future approaches to targeting B-cells other than depletion.

Etiology, pathogenesis, and management of angiosarcoma associated with implants and foreign body: Clinical cases and research updates.

Angiosarcomas are rare and highly malignant soft tissue sarcomas originating from endothelial cells lining the lymphatic or vascular system. While they predominantly emerge from (sub)cutaneous regions, occurrences have been reported throughout the body. The etiology of angiosarcoma remains elusive in most clinical cases. Nevertheless, several prognosis risk factors play a pivotal role, including chronic lymphedema, therapeutic irradiation, environmental carcinogens, familial syndromes, and the presence of foreign materials like metallic objects and biomedical implants. Despite evidence implicating retained foreign material in angiosarcoma development, understanding its prognosis and pathogenesis remains limited. The pathogenesis of angiosarcoma appears to involve a complex interplay of chronic inflammation, tissue remodeling, and genetic factors that create a conducive microenvironment for malignant transformation. Management of these sarcomas remains challenging due to their infiltrative nature owing to the high chance of metastasis and local recurrence. The primary treatment modalities currently include surgery, radiotherapy, and chemotherapy, but recent advances in targeted immunotherapy and gene therapy hold promise for more effective approaches. This comprehensive review delves into the potential etiological and pathogenic roles of foreign materials, such as metallic objects, biomedical implants, and biomaterials, in the development of angiosarcoma. Further research into the underlying molecular mechanisms could provide valuable insights for tailored management and developing novel targeted therapeutic strategies.

The glucocorticoid receptor acts locally to protect dystrophic muscle and heart during disease.

Absence of dystrophin results in muscular weakness, chronic inflammation and cardiomyopathy in Duchenne muscular dystrophy (DMD). Pharmacological corticosteroids are the DMD standard of care; however, they have harsh side effects and unclear molecular benefits. It is uncertain whether signaling by physiological corticosteroids and their receptors plays a modifying role in the natural etiology of DMD. Here, we knocked out the glucocorticoid receptor (GR, encoded by Nr3c1) specifically in myofibers and cardiomyocytes within wild-type and mdx52 mice to dissect its role in muscular dystrophy. Double-knockout mice showed significantly worse phenotypes than mdx52 littermate controls in measures of grip strength, hang time, inflammatory pathology and gene expression. In the heart, GR deletion acted additively with dystrophin loss to exacerbate cardiomyopathy, resulting in enlarged hearts, pathological gene expression and systolic dysfunction, consistent with imbalanced mineralocorticoid signaling. The results show that physiological GR functions provide a protective role during muscular dystrophy, directly contrasting its degenerative role in other disease states. These data provide new insights into corticosteroids in disease pathophysiology and establish a new model to investigate cell-autonomous roles of nuclear receptors and mechanisms of pharmacological corticosteroids.

The role of aetiology in cardiac manifestations of chronic kidney disease: the CPH-CKD ECHO study

PurposeWe investigated the associations between cardiac parameters and aetiologies of CKD in an exploratory study.MethodsThe study population consisted of 883 participants, 174 controls and 709 patients with aetiologies of CKD including diabetic nephropathy/renovascular KD in diabetes mellitus, hypertensive/renovascular nephropathy, tubulointerstitial nephritis, glomerulonephritis/vasculitis, polycystic KD (PKD), and CKD of unknown origin. Echocardiographic measures included left ventricular (LV) ejection fraction, global longitudinal, area, and radial strain, E/e’ ratio, and LV mass index. These were compared between each aetiological group and controls in unadjusted and adjusted analysis.ResultsIn unadjusted analysis, patients with diabetic nephropathy/renovascular KD in diabetes mellitus, had impaired LV ejection fraction (Median [IQR]: 56% [49.9,60.69] vs. 60.8% [57.7,64.1]), global longitudinal (mean ± SD: 13.1 ± 3.5% vs. 15.5 ± 2.6%), area (24.1 ± 5.8% vs. 28.5 ± 4.2%), and radial strain (36.2 ± 11.2% vs. 44.1 ± 9.7%), and increased LV mass index (89.1 g/m2 [71.8,104.9] vs. 69,0 g/m2 [57.9,80.8]) and E/e’ ratio (10.6 [8.5,12.6] vs. 7 [5.8,8.3], p < 0.001 for all) compared with controls. Associations were similar for CKD of unknown origin. Patients with hypertensive/renovascular nephropathy had impaired global longitudinal and area strain, and higher E/e’ ratio. Patients with glomerulonephritis/vasculitis had higher LV mass index, while patients with PKD had better global longitudinal strain than controls. All findings remained significant in adjusted analysis, except for the impaired global longitudinal strain in hypertensive/renovascular nephropathy.ConclusionGlomerulonephritis/vasculitis, hypertensive/renovascular nephropathy, CKD of unknown origin, and diabetic nephropathy/renovascular KD in diabetes mellitus were increasingly associated with adverse cardiac findings, while PKD and tubulointerstitial nephritis were not. Aetiology might play a role regarding the cardiac manifestations of CKD.Graphical A graphical summary of the study population and main results. Abbreviations: DN = Diabetic nephropathy and renovascular kidney disease in diabetes mellitus, PKD = Polycystic kidney disease, CKDu = Chronic kidney disease of unknown origin, LVEF = Left ventricular ejection fraction, LVMi = Left ventricular mass index, E/e’ ratio = Early mitral inflow velocity to mitral annular early diastolic velocity ratio, GLS = Global longitudinal strain, GAS = Global area strain, GRS = Global radial strain.

Nutritional support for immune health during infections

Infectious diseases are common in underdeveloped and developing countries. Malnutrition plays an important role in disease etiology, remarkably increasing morbidity and mortality risks during the early stages of life, such as infancy and childhood. Nutrients such as glutamine, arginine, omega-3 and omega-6 fatty acids, zinc, selenium, iron, vitamins A, C, E, D and B6, components of breast milk, and adequate energy intake strengthen the immune system, reduce infection risk, and play a key role in combating diseases. This review highlights the importance of nutrition for the treatment of infectious diseases.

Possible etiological role of impaired endogenous double strand RNA editing in β-cells in type 1 diabetes.

Proposed mechanisms by which disruption of endogenous dsRNA editing in β-cells leads to type 1 diabetes-like phenotypes in βAdarKO mice. Disruption of endogenous dsRNA editing in β-cells initiates IFN responses, thereby inducing pancreatic islet inflammation and β-cell dysfunction. Hyperglycemia induced by β-cell dysfunction further promotes islet inflammation, likely via increased dsRNA resulting from increased β-cell workload, thereby producing a vicious cycle. The mechanism by which impairment of dsRNA editing is integrated with autoimmune-mediated pathogenesis of type 1 diabetes remains to be clarified.

Premenstrual syndrome: new insights into etiology and review of treatment methods.

Premenstrual syndrome (PMS) is a common disorder affecting women of reproductive age, with an estimated global prevalence of 47.8%, with severe symptoms occurring in 3-8%, significantly affecting daily functioning. GABA conductance and changes in neurosteroid levels, particularly allopregnanolone, are suspected to play a substantial role in the disorder's etiology. In this paper, we provide an overview of recent reports on the etiology and recognized therapeutic approaches, encompassing both pharmacological and non-pharmacological interventions. Our examination includes studies on SSRIs, hormonal agents, neurosteroids, supplementation, and therapeutic roles. We aim to determine the most favorable treatment regimen by comparing medication effects and alternative methods. The treatment of PMS is crucial for enhancing the quality of life for affected women. Medications used in PMS treatment should be individually selected to achieve the best therapeutic effect, considering the clinical situation of the patients.

Brain compensatory mechanisms in depression and memory complaints in fibromyalgia: the role of theta oscillatory activity.

The different clinical presentations of fibromyalgia syndrome (FMS) might play independent roles in the unclear etiology of cognitive impairments and depressive symptoms seen in patients with FMS. Understanding how these clinical presentations are associated with the clinical and neurophysiological aspects of FMS is important for the development of effective treatments. To explore the relationship of memory complaints and depressive symptoms with the different clinical and neurophysiological characteristics of FMS. Cross-sectional data analysis from a randomized clinical trial. Baseline demographics and data on physical fitness, sleep, anxiety, depression, cortical excitability, and pain (clinical and mechanistic) from 63 subjects with FMS were used. Multiple linear and logistic association models were constructed. Final regression models including different sets of predictions were statistically significant (P < .001), explaining approximately 50% of the variability in cognitive complaints and depression status. Older subjects had higher levels of anxiety, poorer sleep quality, lower motor threshold, and higher relative theta power in the central area and were more likely to have clinical depression. Higher anxiety, pain, and theta power were associated with a higher likelihood of memory complaints. Depression symptoms seem to be associated with transcranial magnetic stimulation-indexed motor threshold and psychosocial variables, whereas memory complaints are associated with pain intensity and higher theta oscillations. These mechanisms might be catalyzed or triggered by some behavioral and clinical features, such as older age, sleep disruption, and anxiety. The correlation with clinical variables suggests that the increasing of theta oscillations is a compensatory response in patients with FMS, which can be explored in future studies to improve the treatment of FMS. ClinicalTrials.gov ID NCT03371225.

Decreased Circulating Very Small Low-Density Lipoprotein is Likely Causal for Age-Related Macular Degeneration

Abnormal changes in metabolite levels in serum or plasma have been highlighted in several studies in age-related macular degeneration (AMD), the leading cause of irreversible vision loss. Specific changes in lipid profiles are associated with an increased risk of AMD. Metabolites could thus be used to investigate AMD disease mechanisms or incorporated into AMD risk prediction models. However, whether particular metabolites causally affect the disease has yet to be established. A 3-tiered analysis of blood metabolites in the United Kingdom (UK) Biobank cohort to identify metabolites that differ in AMD patients with evidence for a putatively causal role in AMD. A total of 72376 donors from the UK Biobank cohort including participants with AMD (N=1353) and non-AMD controls (N=71023). We analyzed 325 directly measured or derived blood metabolites from the UK Biobank for 72376 donors to identify AMD-associated metabolites. Genome-wide association studies for 325 metabolites in 98316 European participants from the UK Biobank were performed. The causal effects of these metabolites in AMD were tested using a 2-sample Mendelian randomization approach. The predictive value of these measurements together with sex and age was assessed by developing a machine learning classifier. Evaluating metabolic biomarkers associated with AMD susceptibility and investigating their potential causal contribution to the development of the disease. This study noted age to be the prominent risk factor associated with AMD development. While accounting for age and sex, we identified 84 metabolic markers as significantly (false discovery rate-adjusted P value < 0.05) associated with AMD. Lipoprotein subclasses comprised the majority of the AMD-associated metabolites (39%) followed by several lipoprotein to lipid ratios. Nineteen metabolites showed a likely causative role in AMD etiology. Of these, 6 lipoproteins contain very small, very low-density lipoprotein (VLDL), and phospholipids to total lipid ratio in medium VLDL. Based on this we postulate that depletion of circulating very small VLDLs is likely causal for AMD. The risk prediction model constructed from the metabolites, age and sex, identified age as the primary predictive factor with a much smaller contribution by metabolites to AMD risk prediction. This study underscores the pronounced role of lipids in AMD susceptibility and the likely causal contribution of particular subclasses of lipoproteins to AMD. Our study provides valuable insights into the metabopathological mechanisms of AMD disease development and progression.