Methods of multiple sclerosis (MS) treatment are evolving rapidly, with numerous classes of disease-modifying therapies (DMTs). A more aggressive approach to early and effective treatment of MS with a defined treatment target increases the chance of achieving a state of no evidence of disease activity (NEDA). Currently, B cell-depleting monoclonal antibodies have been proven as a highly effective strategy for the treatment of relapsing-remitting MS (RRMS). Ofatumumab (OFA), an anti-CD-20 monoclonal antibody, is effective in treatment of RRMS, as it positively affects relapse rates, magnetic resonance imaging (MRI) measures of disease activity, and disability progression. A retrospective observational study was conducted in six MS clinical centers in Poland, including a cohort of patients with RRMS treated with OFA over a 2-year period. The results of this study showed a statistically significant decrease in the relapse activity of the disease in the course of a year of OFA therapy. The percentage of patients free of relapses increased from 45% before treatment to 88% after 1 year of follow-up. Moreover, the disability assessment index measured by the Expanded Disability Status Scale (EDSS) remained stable after 2 years of follow-up. In the present study, the high efficacy of OFA therapy in reducing recurrent disease activity, as well as in inhibiting disability progression, with a favorable safety profile, was confirmed. Moreover, it was emphasized that to achieve the best possible inhibition of disease activity and its progression, it is necessary to implement the treatment as soon as possible after the diagnosis.
This project intended to develop and validate a diabetes prediction model for high-risk populations based on machine learning algorithms. A total of 2,355 samples from the National Health and Nutrition Examination Survey (NHANES) database covering three cycles from 2013 to 2018 were included. The data were divided into training and testing sets in a 7 : 3 ratio. Nineteen risk prediction factors were selected as feature variables, including demographic baseline data, measurement data, medical history, and psychological health. Five machine learning models - decision tree, random forest (RF), multilayer perceptron (MLP), Adaboost, and Extreme Gradient Boosting (XGBoost) - were developed based on the data and variables mentioned above. Model performance was evaluated using accuracy, sensitivity, specificity, the area under curve (AUC) values of receiver operating characteristic (ROC) curves, and Matthews Correlation Coefficient (MCC) scores. Finally, the Shapley feature importance measurement tool was employed to select features in the optimal model. The present work ultimately included 2,355 individuals at high risk of diabetes for analysis, with 260 cases of diabetes and 2,095 cases without diabetes. Among the five machine learning models established in this project., the RF and XGBoost models exhibited better overall performance compared to other models. In the test set, the RF model had an AUC of 0.896, accuracy of 0.784, sensitivity of 0.739, specificity of 0.849, and MCC of 0.418. The XGBoost model had corresponding values of AUC as 0.903, accuracy of 0.815, sensitivity of 0.962, and MCC of 0.443. According to the importance analysis of features in these two optimal models, waist circumference, age, BMI, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), education level, poverty income ratio (PIR), Patient Health Questionnaire (PHQ)-9 score, and race were the top ten key risk factors for diabetes in the high-risk population. The RF and XGBoost machine learning models demonstrated strong performance in predicting the occurrence of diabetes in high-risk populations. These models can aid in developing more precise intervention measures and personalized treatment plans to effectively reduce the incidence of diabetes and related risks in this population.
Transition zone (TZ) prostate cancer poses diagnostic challenges due to overlapping imaging features with benign prostatic hyperplasia (BPH). This study aimed to investigate whether Prostate Imaging Reporting and Data System (PI-RADS) v2.1 combined with prostate-specific antigen density (PSAD) can enhance diagnostic accuracy in distinguishing TZ cancer from BPH. The retrospective study included 377 patients divided into two groups: the TZ cancer group (n = 139) and the BPH group (n = 238). Two radiologists independently reviewed prostate MR images of each patient and assigned a PI-RADS score for the TZ lesion. Clinical characteristics were compared between the two groups using the χ2 test, t-test, or Mann-Whitney U-test. The diagnostic performance of PI-RADS scores, PSAD, and the combined parameters was determined by ROC curve analysis. Statistically significant differences were found in PSA, prostate volume, PSAD, and PI-RADS scores between the two groups (all p < 0.0001). No difference in age was observed between the two groups (p = 0.602). The area under the curve (AUC) for PI-RADS v2.1 alone was 0.802 (95% CI: 0.759-0.841) with a sensitivity of 79.14% and specificity of 74.37% at a cutoff of ≥ 4. The AUC for PSAD alone was 0.808 (95% CI: 0.765-0.847) with a sensitivity of 79.14% and specificity of 77.31% at a cutoff of 0.22 ng/ml/ml. Combining PI-RADS and PSAD yielded an AUC of 0.873 (95% CI: 0.835-0.905), with a sensitivity of 79.26% and specificity of 86.55%. The combination of PI-RADS v2.1 and PSAD enhances the diagnostic accuracy for TZ cancer, thereby reducing unnecessary invasive procedures.
Communication and interpersonal skills are fundamental to effective medical practice and can significantly influence adherence to medical recommendations and treatment outcomes. This study aimed to identify both strengths and areas requiring support in interpersonal skills among general practitioners in Poland. The study was conducted using the computer-assisted telephone interview (CATI) method with a sample of 600 general practitioners working in public and private primary care clinics in Poland. The Interpersonal Communication Skills Inventory (Learning Dynamics, 2002) was used to assess communication skills. The average score obtained by respondents was 72 out of a possible 120 points. Analysis of specific communication skill domains indicated that the strongest area was Sending Clear Messages (M = 21.19, SD = 5.01). However, Listening (M = 16.68, SD = 4.45) and Giving and Receiving Feedback (M = 16.87, SD = 5.12) were identified as areas requiring improvement. Variations in communication skill levels were associated with factors such as gender, age, years of professional experience, self-assessed communication skills, perceived adequacy of consultation time, perceived need for practical communication training and prior participation in doctor-patient communication workshops. The findings indicate that the surveyed general practitioners may have an insufficient awareness of their own communication skills. The communication skills of Polish general practitioners require particular attention, especially in the areas of Listening and Giving and Receiving Feedback. No overall improvement in communication skills was observed with increasing professional experience, suggesting that targeted training may be necessary to enhance them.
This population-based study aimed to evaluate the survival benefits of radiotherapy, chemotherapy, chemoradiotherapy, and non-chemoradiotherapy in patients with unresectable intrahepatic cholangiocarcinoma (ICC). We used the Surveillance, Epidemiology, and End Results (SEER) database's SEER*stat software (version 8.3.5) to gather data of patients diagnosed with unresectable ICC from 2000 to 2018. Survival curves were plotted using the Kaplan-Meier method, comparing the overall survival (OS) and cancer-specific survival (CSS) among patients who underwent radiotherapy, chemotherapy, chemoradiotherapy, or no therapy at all. Univariate and multivariate Cox regression models were employed to analyze the prognostic factors affecting these unresectable ICC patients. From 2000 to 2018, we identified 11,753 cases of unresectable ICC from the SEER database. Of these, 4,531 (38.5%) patients underwent chemotherapy alone, 482 (4.1%) patients underwent radiotherapy alone, and 996 (8.5%) patients received a combination of both. A total of 5,744 (48.9%) patients did not receive chemoradiotherapy. The median OS was 8 months (95% CI: 8--9 months) for patients receiving chemotherapy alone, 7 months (95% CI: 6-8 months) for radiotherapy alone, 12 months (95% CI: 11-13 months) for chemoradiotherapy, and 3 months (95% CI: 3-3 months) for those not receiving chemoradiotherapy. The CSS findings were consistent with the OS results. The Cox regression models indicated that patient age, sex, grade classification, tumor diameter, and treatment modality were independent prognostic factors for unresectable ICC patients (p < 0.05). Chemoradiotherapy can enhance the OS and CSS of patients with unresectable ICC, compared to the use of chemotherapy or radiotherapy alone.
Interstitial lung disease (ILD) is a common complication of connective tissue disease (CTD), which seriously affects the prognosis of patients. The abnormal expression of tumor markers in non-neoplastic diseases may be related to the occurrence and development of CTD-ILD. This study aimed to explore the detailed clinical characteristics of CTD-ILD, and to analyze their association with serum tumor markers. The clinical data of 128 patients with CTD-ILD were retrospectively analyzed. Seventy-nine ILD patients without CTD were enrolled as the non-combined group. Clinical data included imaging manifestations, laboratory indices and tumor markers such as carbohydrate antigen (CA) 125, CA153, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) antigen were collected. ROC curve analysis was used to assess the clinical value of these markers. The proportion of clinical manifestations such as arthralgia, rash, Raynaud's phenomenon, dry mouth and dry eyes in the combined group was higher than in the non-combined group (p < 0.05). The serum albumin and total protein levels in the combined group were lower than in the non-combined group (p < 0.001). The levels of CA125, CA153, CEA, SCC, and NSE in the combined group were higher than in the non-combined group (p < 0.001). The AUC of combined detection of each index was 0.917, with a sensitivity of 97.47% and a specificity of 76.56%. The main clinical manifestations for CTD-ILD patients were arthralgia, rash, Raynaud's phenomenon, and dry mouth and eyes. The combined detection of tumor markers had high evaluation value.
Oxytocin receptor (OXTR) gene variations are associated with empathy, trust, emotional stability, stress reactivity, social bonding and attachment behaviors. We aimed to explore the impact of three OXTR gene variations (rs53576, rs237902, rs2254298) in susceptibility to panic disorder (PD). We also investigated the possible effects of these variants on separation anxiety scale scores in patients, with a comprehensive approach covering environmental adversity effects. The hypothesis was studied in PD patients and healthy controls with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. By applying the Separation Anxiety Symptom Inventory (SASI) and the Adult Separation Anxiety Questionnaire (ASA), the relationships between the OXTR gene variants and these scales were also evaluated comprehensively. A statistically significant association was found for OXTR rs237902; presence of the A allele was associated with a 1.585-fold increase in probability of PD. Moreover, all of the analyzed OXTR variants were found to be associated with childhood and adult separation anxiety in the patients in the combined analyses of various demographic and clinical data; striking associations of AA genotype with SASI and ASA scores were observed in these models. The study supports the involvement of oxytocinergic gene variants in PD. It also represents one of the most comprehensive models examining gene-environment (G × E) interactions in this context.
Although malignancies during pregnancy are relatively rare, breast cancer is the most common neoplasm affecting pregnant women. Diagnostic workup and multimodal treatment of breast cancer during pregnancy must be weighed against the potential risk to the fetus. With the increasing number of breast cancer diagnoses during pregnancy, this narrative review aimed to outline the epidemiological and molecular background, followed by presenting available therapeutic options. Surgery remains the treatment of choice among patients with breast cancer during pregnancy. However, systemic therapy based on anthracyclines, fluoropyrimidines, taxanes, and platinum derivatives is possible after 12 weeks of gestation and can be administered in both neoadjuvant and adjuvant settings. Hormone therapy should not be used during pregnancy as it may affect the fetus. Studies suggest that estrogen or progestogen therapy during pregnancy may cause malformations in children exposed in utero. One known phenomenon is the congenital fetal defect Goldenhar syndrome (manifested by hemifacial hypoplasia and genital malformations). There are no absolute contraindications for radiotherapy in pregnant patients. The potential benefits and risks of radiotherapy, including the potential risk to the fetus, should be carefully considered. Although it is recommended that radiation be delayed until after delivery, the critical threshold for teratogenic effects has been set at 0.1 Gy. The dose can be further reduced by using additional shielding in the pelvic region. Importantly, the sensitivity of fetal tissues to radiation and the risk of radiation-induced toxicity depend on gestational age. Novel diagnostic and therapeutic directions are being investigated. Due to its complexity, the treatment process should be managed by a multidisciplinary team, in which the presence of an oncologist, surgical oncologist, obstetrician, and neonatologist is essential.
Ulcerative colitis (UC) is a chronic and persistent inflammatory bowel disease with limited clinical treatment options and significant therapeutic challenges. This study aimed to evaluate whether the therapeutic effect of curcumin against ulcerative colitis is positively correlated with its inhibition of angiogenesis and to elucidate the underlying angiogenesis-related molecular mechanism. A multi-database analysis was performed to predict the possible targets involved in curcumin inhibition of UC. Tube formation and aortic ring assays were used to evaluate angiogenesis in vitro. A dextran sulfate sodium (DSS)-induced ulcerative colitis mouse model was used to evaluate curcumin's effect on UC. We first employed a comprehensive multi-database analysis to identify overlapping targets connecting curcumin, ulcerative colitis, and angiogenesis, leading to the identification of signal transducer and activator of transcription 3 (STAT3) as a potential mediator of this process. In vitro experimental results demonstrated that curcumin significantly inhibited tube formation in human umbilical vein endothelial cells (HUVEC) and suppressed endothelial sprouting in rat aortic rings. Furthermore, curcumin downregulated the expression of vascular endothelial growth factor (VEGF) in HUVEC cells and concurrently inhibited the expression of phosphorylated JAK2 and phosphorylated STAT3 (Y705). Notably, the addition of VEGF partially reversed curcumin's inhibitory effects on p-JAK2 and p-STAT3. In vivo studies using a DSS-induced mouse model of ulcerative colitis revealed that curcumin ameliorated DSS-induced colon shortening and various disease symptoms. It also suppressed serum levels of TNF-α and IL-6 and inhibited the expression of STAT3 and VEGF in colonic tissues. Curcumin ameliorates ulcerative colitis through inhibition of the VEGF-mediated JAK2/STAT3 signaling pathway. These findings position curcumin as a potential clinical candidate drug for the treatment of ulcerative colitis.
Chemokine ligand 13 (CXCL13) has been reported to be a valuable diagnostic biomarker in Lyme neuroborreliosis (LNB). However, its utility in the diagnostics of viral and autoimmune (AE) encephalitis still remains unclear. We measured CXCL13 concentrations in cerebrospinal fluid (CSF) samples collected from 21 patients with viral encephalitis (17 cases of herpes simplex viral (HSV) and 4 of enteroviral (EV) encephalitis) and 6 patients with AE (5 subjects with antibodies anti-NMDAR and 1 with anti-GABA) and compared them to those found in patients with LNB (7 subjects) and multiple sclerosis (8 cases) as well as ten control subjects without neuroinflammation. Patients with neuroinflammation had a mean level of CXCL13-CSF of 105 pg/ml compared to 29 pg/ml in controls. The highest mean level of CXCL13 in CSF was detected in LNB patients (233 pg/ml), and the lowest in controls (29 pg/ml). Significant upregulation of CXCL13-CSF levels in LNB patients was observed in comparison to viral encephalitis and MS patients as well as controls. A positive correlation between elevated chemokine levels and cell count in CSF was found in all patients (r = 0.6496; p < 0.0001), as well as in the LNB group when tested alone (r = 0.8428; p = 0.0173). A positive correlation with CSF protein levels was observed in all patients (r = 0.7216; p < 0.0001), and separately in LNB (r = 0.8573; p = 0.0137) and AE patients (r = 0.8885; p = 0.0180). The findings support the utility of CXCL13 measurements in CSF for LNB diagnosis. No specific patterns in CXCL13-CSF levels were associated with viral or autoimmune encephalitis.
Disturbed mitochondrial activity in adipocytes has been proposed as one of the mechanisms involved in metabolic dysfunction in obesity. Glucagon-like peptide receptor agonists (GLP-1RAs) are used to normalize glucose level and reduce body weight. GLP-1 activates intracellular pathways similar to those of irisin, a peptide that modulates metabolism by stimulating the 'browning' of adipocytes. The aim of the study was to investigate the mechanisms of action of the GLP-1RA exendin-4 at the mRNA, protein, and mitochondrial levels in human adipocytes. Human Chub-S7 preadipocytes were differentiated in vitro to mature adipocytes and then stimulated with exendin-4 at 100 nM for 24 h. Expression levels of mRNA and proteins (irisin, adiponectin, visfatin/NAMPT) were measured. Oxygen consumption rates and intracellular ATP content were determined. Exendin-4 enhanced the secretion of irisin and visfatin by adipocytes. Upregulated expression of FNDC5, NAMPT, and UCP2 genes was accompanied by modest changes in mitochondrial activity in exendin-4-treated adipocytes. Exendin-4 exerted a similar effect on mitochondrial oxygen consumption rates as irisin, including increased maximum mitochondrial respiration and reserve capacity with unchanged intracellular ATP. Increasing energy expenditure by exendin-4 may be associated with upregulation of irisin in human adipocytes. Clinical studies are necessary to confirm the hypothesis that nutrients, by stimulating the secretion of GLP-1, may influence the expression of irisin and thus modulate the mitochondrial metabolism of adipocytes.
Mental health disorders and constipation are increasingly prevalent health problems worldwide. Previous studies have reported bidirectional associations between depression, anxiety, sleep disorders, and constipation. However, observational studies have yielded inconsistent results. The associations were examined through a two-sample, bidirectional, univariable, and multivariable Mendelian randomization (MR) study. Summary-level data were obtained from the UK Biobank, large consortia, and the FinnGen consortium. The inverse-variance weighted method was applied as the principal analytical approach, and other additional MR methods (maximum likelihood, MR-RAPS, and MR-PRESSO) were used for sensitivity analyses. Multivariable MR analysis was performed to assess the independent effects of selected exposures. The univariable MR analyses indicated that major depression (MD) (OR = 1.28; 95% CI: 1.12-1.46), broad depression (BD) (OR = 3.72; 95% CI: 1.55-8.97), depressed affect (OR = 1.41; 95% CI: 1.13-1.76), and worry (OR = 1.42; 95% CI: 1.13-1.77) were associated with an increased risk of constipation. There was no evidence supporting the causal effects of anxious feelings, sleep duration, and sleeplessness on constipation. The reverse MR analyses found no reverse causal association of constipation with depression, anxiety, and sleep disorders. In multivariable MR, only MD still had a robust causal association with constipation, while the effect of worry was attenuated to null, and the effects of BD and depressed affect were completely reversed. MD is causally associated with constipation, and worry might also increase the risk of constipation. Future studies are needed to confirm the causality and elucidate the underlying mechanisms.
Neonatal jaundice, a condition characterized by elevated bilirubin levels in newborns, is prevalent, affecting up to 60% of term infants. Previous observational studies have linked neonatal jaundice to an enhanced risk of allergic diseases such as asthma, atopic dermatitis (AD), allergic conjunctivitis (AC), allergic rhinitis (AR), and urticaria. However, the causal relationship remains unclear due to potential confounding factors and reverse causality. We conducted a two-sample MR analysis using genetic variants as instrumental variables. Data from large-scale GWAS in European populations were used, including exposure data for neonatal jaundice and outcome data for five common allergic diseases. MR analysis was performed using the inverse variance weighted (IVW) method, with additional sensitivity analyses conducted using MR-Egger regression, weighted median, simple mode, and weighted mode methods. MR analysis revealed a significant causal association between neonatal jaundice and an increased risk of AD (OR = 1.0141, 95% CI: 1.0041-1.0241, p = 0.006) and AC (OR = 1.0119, 95% CI: 1.0014-1.0226, p = 0.026). No significant association was found between neonatal jaundice and pediatric asthma, urticaria, or AR. Sensitivity analyses indicated no evidence of pleiotropy, and no individual SNPs substantially influenced the results, confirming the robustness of our findings. This study provides evidence for a causal association between neonatal jaundice and an increased risk of AD and AC. These findings suggest that neonatal jaundice may be a modifiable risk factor for AD and AC, highlighting the importance of neonatal jaundice management and further research on potential preventive strategies.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with diverse symptoms and frequent comorbidities, posing diagnostic challenges. Despite advances in ASD awareness and diagnostic methods, significant knowledge gaps persist among healthcare professionals. This study assessed physicians' knowledge of ASD, focusing on symptoms, comorbidities, and diagnostic challenges to enhance patient care. This study, conducted in 2024, involved physicians attending courses at the Center of Postgraduate Medical Education in Warsaw (CMKP). Participation was anonymous and voluntary. Respondents completed the author's own questionnaire and the Knowledge about Childhood Autism among Health Workers (KCAHW) questionnaire to assess autism knowledge across four domains: social interaction impairments, communication issues, obsessive behaviors, and disorder onset and comorbidities. Physicians also provided professional and demographic data. The study included 395 physicians, primarily young (mean age: 31), female (75%), and in early career stages, with most having up to 5 years of experience. While 75% had some contact with individuals on the autism spectrum, only 28% had close family or acquaintances with ASD. Knowledge about autism was moderate, averaging 74% correct responses, with higher accuracy in recognizing social interaction impairments (80%) and repetitive behaviors (78.5%), but lower accuracy regarding comorbidities (63%). Younger, less experienced physicians, women, and those with personal ASD contact had higher knowledge about autism. The study highlights the need for targeted ASD education to address specific knowledge gaps among healthcare professionals, essential for providing informed and compassionate care.
The aim of the study was to identify the key risk factors influencing in-intensive care unit (ICU) mortality of patients with sepsis and develop prognosis prediction models for culture-positive sepsis (CPS) and culture-negative sepsis (CNS) patients. Data were extracted from the MIMIC-IV database, which included 9288 patients with sepsis. The whole sample was divided into CPS (6622 patients) and CNS groups (2666 patients). We established six machine learning models - DT, RF, NB, XGB, GBDT, and NNET - to predict in-ICU death for all study samples, as well as for CPS and CNS subgroups. Model performance was assessed using AUC, accuracy, sensitivity, and specificity. SHapley Additive exPlanations (SHAP) values were used to explain the effect of variables on model results. The in-ICU mortality rate was 54.58% for the whole study sample; the difference in in-ICU mortality between the CPS (55.19%) and CNS (53.04%) groups was not statistically significant. The main significant influential factors identified included Charlson Comorbidity Index (CCI), number of days in hospital, Glasgow Coma Scale (GCS), older age, and total bilirubin (TBil). The XGB model performed best in the overall sample (AUC = 0.782), while the GBDT model was most effective for the CPS group (AUC = 0.7813) and the CNS group (AUC = 0.7582). This study identified key risk factors for in-ICU death in patients with sepsis and highlighted differences in clinical characteristics between patients with CPS and CNS. These findings may contribute to the development of personalized treatment strategies and risk assessment, thereby improving the prognosis of septic patients, especially patients with CNS.
Ketogenic diets (KD) recapitulate certain metabolic aspects of dietary restriction such as reliance on fatty acid metabolism and production of ketone bodies. This study aimed to investigate whether a KD might, like dietary restriction, affect brain functions in epilepsy. Kainic acid (KA) injection was used to establish an epilepsy model in vivo. Histone deacetylation 4 (HDAC4) mRNA expression was determined using RT-qPCR. Protein expression was detected using western blot. Gene expression was determined using immunofluorescence. The release of malondialdehyde (MDA), ferrous iron, and glutathione (GSH) was detected using corresponding commercial kits. The interaction between HDAC4 and transferrin receptor (TFRC) was verified using co-immunoprecipitation assay. Neuronal viability was detected using Cell Counting Kit-8 (CCK-8) assay. Neuronal death was detected using propidium iodide (PI) staining. Epilepsy mediated iron accumulation- and lipid peroxidation-induced neuronal ferroptosis. Interestingly, KD treatment alleviated epilepsy as well as the accumulation of ferrous iron and lipid peroxidation, resulting in the inhibition of neuronal ferroptosis in epileptic models in vivo and in vitro. Mechanically, KD promoted the upregulation of HDAC4, which inhibited the acetylation of TFRC and suppressed its protein expression. However, downregulation of HDAC4 by its specific inhibitor LMK235 promoted the ferroptosis of neurons. Collectively, KD protect against the ferroptosis of neurons in epilepsy via promoting HDAC4-mediated deacetylation and downregulation of TFRC. Therefore, KD may be a promising strategy for epilepsy.
Cardiovascular disease (CVD) and neoplasms are the two leading causes of death worldwide. Previous research has predominantly addressed these conditions separately or focused on specific regions. We aimed to characterize the global co-occurrence pattern of CVD and neoplasms from spatial and temporal perspectives and identify corresponding risk factors across different epidemiological contexts. Using GBD 2021 data, we extracted age-standardized disability-adjusted life year (DALY) rates of CVD and neoplasms and modifiable risk factor exposure from 204 countries and territories (1990-2021). We identified four epidemiological patterns: low-burden, neoplasm-dominant, CVD-dominant, and dual-burden regions. We calculated population attributable fractions (PAF) and integrated machine learning with SHAP values to distinguish intervention priorities. Average annual percentage changes (AAPC) were used to evaluate temporal trends. Each pattern comprised 50-52 countries. Spatial distribution overlapped with socioeconomic development stages and risk factor exposure. Temporal analysis revealed widening global inequality: low-burden regions achieved 3-4% annual reductions while dual-burden regions experienced an increasing burden, creating a 5.8 percentage point gap. High systolic blood pressure was the universal dominant CVD risk factor, accounting for 49.7% of the global burden (49.2-52.4% across patterns). For neoplasms, smoking contributed 18.5% globally but varied dramatically by pattern (10.4-23.4%). Modifiable risk factors' specific combinations greatly influenced global disparities. The co-occurrence of CVD and neoplasms represents interconnected manifestations of different epidemiological transition stages, with concerning divergence between regions. Interventions targeting hypertension control and tobacco cessation, combined with pattern-specific strategies, can fundamentally reduce the global disease burden.
Pregnant women are at increased risk of developing caries and periodontal disease due to hormonal changes during pregnancy. The main preventive measure is health awareness and behaviours supporting oral hygiene. The aim of this study was to assess oral hygiene health behaviours of pregnant women in Poland. The study was conducted using the computer-assisted telephone interviewing (CATI) method, in a group of 1,000 women who were in their second or third trimester of pregnancy. The Hiroshima University Dental Behaviour Inventory (HU-DBI) questionnaire was used to assess oral health behaviours. The HU-DBI index was calculated based on 12 questions verifying the respondents' oral health attitudes and behaviour. The majority of the women participating in the study (62%) assessed the condition of their teeth as good or very good. At the same time, 79.7% of the women reported a history of dental caries treatment. The mean HU-DBI index was 5.6 points. The most frequently indicated health-promoting behaviour for oral hygiene was careful oral cavity brushing. Analysis of factors influencing self-assessed oral health behaviours showed significant differences in the HU-DBI index according to financial situation and educational level. Access to dental care should be promoted among pregnant women, regardless of their socioeconomic status. Oral health care measures for pregnant women should include education, prophylaxis, and treatment. It is important to increase the awareness of the expectant mothers that their oral health behaviour has a very strong impact on both their and their children's health, during the fetal period and from birth on.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has a globally increasing prevalence. Oxidative stress and inflammation, as interdependent processes, play pivotal roles in the pathogenesis of MASLD. Moreover, heritability has a significant impact on MASLD. Hence, to fully understand the nature of complex and multifactorial diseases such as MASLD, it is important to consider the role of genetic and epigenetic factors as essential aspects of a broader context that includes clinical and environmental influences and their interactions when multiple metabolic pathways are involved. While traditional biomarkers may be insufficient in the early stages of this process, new-generation biomarkers and multi-omic approaches hold the potential to contribute to the improvement of disease diagnosis and prognosis. This review article aims to systematically examine oxidative stress and inflammation biomarkers, as well as genetic and epigenetic factors in MASLD, highlighting current diagnostic advances and future perspectives in the field.
Inhibited acute myeloid leukemia (AML) proliferation is accompanied by downregulated peroxisome proliferator-activated receptor α (PPARα), which however can be stabilized via SUMOylation. This study investigated how PPARα SUMOylation impacts AML cell growth. Human AML HL-60 and Tohoku Hospital Pediatrics-1 (THP-1) cells were treated with the PPARα inhibitor GW6471 (10 µM) for 24 and 48 h. THP-1 cells were exposed to the PPARα agonist pirinixic acid (10 µM) following manipulation of the expression of the small ubiquitin-like modifier protein (SUMO)-conjugating enzyme UBC9. The interaction between PPARα and SUMO1 was detected by immunoprecipitation assay. HL-60 and THP-1 cell viability, apoptosis, and ferroptosis were measured via Cell Counting Kit-8 assay, flow cytometry, BODIPY-C11 staining and/or colorimetric assay. UBC9, glutathione peroxidase 4 (GPX4), recombinant solute carrier family 7, member 11(SLC7A11) and PPARα expression levels were analyzed by qRT-PCR or Western blot. GW6471 treatment for 24 and 48 h suppressed viability, promoted apoptosis and lipid peroxidation, increased the level of Fe2+, and decreased the expression of GPX4, SLC7A11 and PPARα in HL-60/THP-1 cells. PPARα antibody induced enrichment of PPARα and SUMO1 in THP-1 cells, which was attenuated after UBC9 silencing. UBC9 silencing resulted in viability decrease, apoptosis and lipid peroxidation promotion, Fe2+ upregulation, and GPX4, SLC7A11, and PPARα downregulation in THP-1 cells, which were all counteracted by pirinixic acid. UBC9 silencing-induced PPARα deSUMOylation induces suppression of AML cell growth by ferroptosis.