Group Of Diseases Research Articles

Comparative characteristics and invasive management in patients with non-ST elevation acute coronary syndromes in two high-volume hospitals from Romania and Germany

Abstract Introduction Cardiovascular disease (CVD) carries the highest mortality burden across Europe, acute coronary syndromes (ACS) being responsible for most CVD-related deaths. However, significant regional differences in ACS management have been reported. Purpose To describe the characteristics and management of patients with higher-risk non-ST elevation ACS (NSTE-ACS) in 2 high-volume hospitals from 2 European countries with different prevalence of CVD and different income (Germany – GER and Romania – RO). Methods All consecutive invasively managed high and very-high risk NSTE-ACS patients admitted in 2022 in two high-volume hospitals from GER and RO were identified. Patient clinical profiles, coronary anatomy, revascularization strategies, and in-hospital outcomes were compared. Results were adjusted for age and gender. Results 707 patients (345 GER, 66.7% male; 362 RO, 71.5% male; p>0.05) were included. RO patients were younger (65.5 vs. 70.1 years), with higher rates of hypertension (88.7% vs. 82.0%), dyslipidemia (95.6% vs. 81.7%), diabetes (46.1% vs. 34.5%), and active smoking (37.3% vs. 23.5%) (all p<0.05); whereas GER patients had higher rates of atrial fibrillation (36.2% vs. 23.2%), chronic respiratory disease (24.6% vs. 10.5%), sleep apnoea (9.0% vs. 1.4%), thyroid disorders (24.1% vs. 6.4%), and prior revascularization by percutaneous coronary interventions (PCI) (36.5% vs. 20.2%) or coronary artery bypass grafting (CABG) (15.7% vs. 3.0%) (all p<0.05). Mean left ventricular ejection fraction (LVEF) was lower in the RO cohort (43.4% vs. 48%, p<0.001). Rates of myocardial infarction diagnosed by high-sensitivity troponin I assays (88.7% GER, 87.6% RO), and median diagnosis-to-cathlab intervals (12.8 hours GER, 15.5 hours RO) were similar (all p>0.05). In the obstructive coronary artery disease (CAD) group (80.3% GER, 84.3% RO), no differences were found in multivessel disease rates (67.1% GER, 69.8% RO) or mean SYNTAX score (18.6 GER, 16.9 RO) (all p>0.05). For type 1 NSTE-ACS (67% GER vs. 79% RO, p<0.001), PCI represented the main revascularization method (88.3% GER vs. 78.3% RO, p<0.05). Excluding patients with prior CABG undergoing PCI, complete revascularization (residual SYNTAX score ≤8), was reported in 77.1% GER and 84.4% RO of the PCI cases (p>0.05). Intravascular imaging was used in 28.4% of PCIs in GER, and in none in RO. In-hospital mortality (7.0% GER, 6.8% RO), and rates of major adverse cardiovascular events, defined as a composite of death, myocardial infarction, and stroke (8.1% GER, 9.1% RO), were similar (all p>0.05). Conclusions Higher-risk NSTE-ACS patient profiles mirror overall country CVD risk patterns. Compared to Germany, patients in Romania are younger, with a higher CVD risk factor burden, lower LVEF, underdiagnosis of major non-CVD comorbidities, and delayed CAD diagnosis. Despite similar guideline-directed management and in-hospital outcomes in both centres, these aspects may influence the long-term prognosis.

Bibliographic update about hypertensive disorders of pregnancy intervention studies and their importance

Introduction: cardiovascular diseases represent one of the main causes of death and disability in women, in turn, multicausal hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, preeclampsia/eclampsia, and chronic hypertension with overlapping preeclampsia/eclampsia. The objective was to describe the importance of the intervention studies about hypertensive disorders of pregnancy. Methods: a bibliographic review of 28 articles in Spanish and English, related to the subject, from databases such as SciELO, Pubmed, Scopus, Springer, where more than 60% are from the last 6 years, was carried out.Results: epidemiological data show the high negative impact on obstetric and neonatal health in these entities, emerging as a problem that has continued to affect the good health results in the sector. Added to the neglect of prenatal care, the lack of preparation/skills for the detection and treatment of these pathologies in health personnel, and the lack of knowledge of the pathologies by patients negatively influences the diagnosis. Education is an important means to address reproductive health problems; the proper understanding of a disorder contributes to its prevention, control and management.Conclusions: hypertensive disorders of pregnancy constitute a diverse group of diseases that cause maternal and fetal death. Health education through population-based interventions contributes to reproductive health care and the early detection and treatment of hypertensive disorders

Climate change and emerging infections: Risks, adaptation and response

Abstract Background Weather and changing climate are key drivers of the emergence, re-emergence and spread of infectious diseases globally. However, approaches to emerging infections and climate strategies are still largely being developed separately missing the opportunities for integrated climate adaptation actions to address infectious diseases. Description To inform the development of the UK national emerging infectious diseases plan, a literature review of the current and projected risks from extreme weather events and climate change on emerging infections in the UK is currently underway. This will support further work examining and co-designing adaptation options in the context of preparedness and response to emerging infections. Results Key preliminary findings from the literature review have indicated risks predominantly from evolving patterns of vector borne diseases as climatic conditions and habitat suitability of pathogens change. Changing temperatures and hotter summer temperatures have been associated with changing food-borne infection patterns. Further risks driven by extreme weather, including flooding and droughts, could perpetuate changes in water-borne infection patterns. Adaptation actions focussed on these infectious disease groups are currently under review and will cover risk assessment, data and surveillance, preparedness and response. Lessons This work integrates climate action with action on emerging infectious diseases. By examining the evidence on climate sensitive infections and co-designing solutions across teams, awareness is being raised and relationships and infrastructures built to better prepare and respond to both fundamental global public health challenges.

Differences in clinical characteristics, angina, and quality of life among patients with microvascular vs vasospastic angina and no obstructive coronary artery disease (ANOCA)

Abstract Background In patients with angina and no obstructive coronary disease (ANOCA), the underlying pathophysiology includes microvascular angina (endothelial-dependent and independent coronary microvascular dysfunction (CMD)) and vasospastic angina (microvascular spasm and epicardial spasm) diagnosed with invasive coronary functional angiography (CFA). However, whether there are differences in demographics, clinical characteristics, and outcomes by underlying diagnosis is unknown. We hypothesize that microvascular angina patients will be older and have more cardiovascular risk factors and worse outcomes than the vasospastic angina group. Objective To explore the differences in demographics, risk factors, and outcomes in ANOCA patients with microvascular and vasospastic angina. Methods A prospective registry-based cohort study of consecutive CFA was performed in 156 ANOCA patients between 2020 and 2023 using the Doppler-tipped guide wire method. Patients were classified into microvascular angina, vasospastic angina, and mixed disease. Microvascular angina was defined as endothelial-independent CMD (coronary flow reserve [CFR] < 2.5 in response to adenosine) and/or endothelial-independent CMD (coronary blood flow [CBF] < 50% or no change in vessel diameter in response to 54 mcg intracoronary acetylcholine). Vasospastic angina as microvascular (<90% constriction) and epicardial spasm (>90% constriction) to 108 mcg intracoronary acetylcholine. The mixed disease group included microvascular and vasospastic angina. Validated questionnaires evaluated angina (SAQ-7), functional capacity (DASI), dyspnea severity (UCSD SOB), and perceived stress (PSS) were obtained from patients at office visits prior to undergoing CFA. Results Among 156 ANOCA patients, 114 had microvascular angina, 10 had vasospastic angina, and 32 had mixed disease. The average age was 58.5 (SD 11.2) years. Demographics and prevalence of risk factors, such as hypertension, hyperlipidemia, or diabetes, showed no significant differences among the microvascular, vasospastic, or mixed disease groups. The prevalence of heart failure with preserved ejection fraction (HFpEF) was high across the groups, and outcomes did not differ significantly among them. The SAQ-7 score average ranged from 16.9 to 40.3, consistent with moderate to severe angina, and the DASI score ranged from 32.2 to 34.9, consistent with moderate functional capacity. Dyspnea severity ranged from 30 to 41, consistent with low to moderate severity, and perceived stress ranged from 11.5 to 13, consistent with low to moderate stress among all participants. Conclusion In patients with ANOCA undergoing invasive CFA, demographics, cardiovascular risk factors, and outcomes were similar regardless of underlying diagnosis. We demonstrate a high prevalence of risk factors and HFpEF and evidence of moderate to severe symptoms and functional capacity in ANOCA patients across all diagnoses.Abbreviation explanation for table 1

Effects of the Prenatal Maternal Health Status on Calf Disease Prevalences and Respective Genetic Parameter Estimates in German Holstein Cattle.

The aim of the present study was to infer phenotypic responses and genetic parameters of the F1 calf diseases diarrhoea (DIAR) and pneumonia (PNEU) in dependency of the prenatal maternal health status (PMHS) of the dam and of the herd-calving year. The PMHS considered diagnoses for the cow disease mastitis (MAST) and claw disorders (CD) during gestation of F0 dams. Furthermore, 305-d milk production traits of F1 offspring from either healthy or diseased dam groups were compared. The study comprised 20,045 female calves (F1 = generation 1) and their corresponding dams (F0 = parental generation 0), kept in 41 large-scale herds. All F1 calves were from their dams' 2nd parity, implying that all dam (maternal) diseases were recorded during the first lactation and dry period of the dams. The F1 calves were phenotyped for DIAR up to 30 days post-partum, and for PNEU up to 180 days of age. At least one entry for the respective disease implied a score = 1 = sick, otherwise, a score = 0 = healthy, was assigned. Production records of the 10,129 F1 cows comprised 305-d records in first lactation for milk yield (MY), protein yield (PY) and fat yield (FY). Linear and generalised linear mixed models were applied to infer phenotypic responses of F1 traits in dependency of the PMHS for CD and MAST. A diagnosis for MAST or CD in F0 cows during gestation was significantly (p ≤ 0.05) associated with an increased prevalence for DIAR and PNEU, with pairwise differences of least-squares-means between calves from healthy and diseased cow groups up to 3.61%. The effects of PMHS on 305-d production traits in offspring were non-significant (p > 0.05). In bivariate genetic analyses, DIAR and PNEU were defined as different traits according to the PMHS, i.e., DIAR-MASThealthy and DIAR-MASTdiseased, DIAR-CDhealthy and DIAR-CDdiseased, PNEU-MASThealthy and PNEU-MASTdiseased, and PNEU-CDhealthy and PNEU-CDdiseased. The direct heritabilities for DIAR and PNEU were quite similar in the healthy and respective diseased dam group. Slightly larger direct heritabilities in the diseased dam groups were due to increased genetic variances. Maternal heritabilities were quite stable and smaller than the direct heritabilities. In random regression models, genetic parameters for DIAR and PNEU were estimated along the continuous herd-calving-year prevalence scale, considering a prevalence for MAST and CD (based on the 20,045 dam records plus 16,193 herd contemporary records) in the range from 0% to 30%. Direct heritabilities for PNEU were quite stable along the herd-calving-year gradient for MAST and CD. For DIAR, we observed stronger estimate fluctuations, especially increasing direct heritabilities in dependency of the herd-calving-year prevalence for MAST from 0.13 (at a MAST prevalence of 0%) to 0.30 (at a MAST prevalence of 30%). Consequently, obvious genotype x herd-calving-year PMHS interactions were observed for DIAR on the prenatal MAST scale, with a minimal correlation of 0.48 between direct genetic effects at 0% MAST prevalence and at 30% MAST prevalence. The correlations between direct genetic and maternal genetic effects were antagonistic at all herd-calving-year prevalence levels, displaying strongest fluctuations for "DIAR-MAST." The genotype x herd-calving-year PMHS interactions for DIAR suggest consideration of specific sires according to the herd health status for CD and for MAST.

Investigation of Fibrillar Aggregates Formed by Pathogenic Pre-Pro-Vasopressin Mutants that Cause ADNDI.

Aggregations of unfolded or misfolded proteins, both inside and outside cells, are implicated in numerous diseases, collectively known as amyloidosis. Particularly, Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare disease caused by mutations in the AVP-NPII gene, leading to the inability to secrete arginine vasopressin (AVP). These misfolded proteins accumulate within the endoplasmic reticulum (ER), causing cellular dysfunction. This study aimed to investigate the formation of amyloid-like aggregates within the cell resulting from misfolded mutant precursor proteins, which induce disulfide-linked oligomers due to the G45C, 207_209delGGC, G88V, C98X, C104F, E108D-1, E108D-2 and R122H mutations identified by our group in the AVP-NPII gene of ADNDI patients. De-glycosylation studies were performed to analyze the glycosylation patterns of mutant protein precursors. The involvement of these precursors in the ER-related degradation pathway was studied by conducting protease inhibition experiments. Disulfide-linked oligomer analysis determined the oligomerization status of the mutant precursors. Immunofluorescence and electron microscopy studies provided evidence of aggregate structures in the ER lumen. In vitro studies involving bacterial expression and fibril formation in E. coli. Our findings demonstrated that the N-glycan structure of mutant precursors remains intact within the ER. Protease inhibition experiments indicated the involvement of these precursors in the ER-related degradation pathway. Disulfide-linked oligomer analysis revealed homo-oligomer structures in mutations. Immunofluorescence and electron microscopy studies confirmed the presence of aggregate structures in the ER lumen. In vitro studies showed that mutant precursors could form fibril structures in E. coli. Our study may support the idea that ADNDI belongs to the group of neurodegenerative diseases due to the formation of fibrillar amyloid aggregates in the cell.

Analysis of the relationship between sleep-related disorders and cadmium in the US population.

Cadmium is a heavy metal that accumulates in the body due to environmental and occupational exposure. The neurotoxicity of cadmium received increasingly attention in recent years. Sleeping is regulated and coordinated by nervous system, however, little is known about the relationship between cadmium and sleep. This study aimed to examine the relationship between blood cadmium concentrations and sleep-related disorders in US adults. This cross-sectional study used data on blood cadmium and sleep from the 2005-2008 and 2015-2020 National Health and Nutrition Examination Survey (NHANES). Weighted multiple regression, generalized weighted modeling, and weighted restricted cubic splines (RCS) were utilized to investigate the association between blood cadmium and sleep outcomes (sleep duration, trouble sleeping, symptoms of obstructive sleep apnea (OSA) and daytime sleepiness). Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, gender, ethnicity, education level, marital status, smoking status, alcohol consumption, diabetes mellitus (DM), cardiovascular disease (CVD) and hypertension groups. In 19,152 participants, the median blood cadmium concentration was 0.48 (IQR: 0.28, 0.82)μg/L. Compared with the lowest reference quartile, participants in the higher quartile had a significantly higher risk of insufficient sleeping (<7 h/night) in crude model (OR 1.53, 95% CI 1.33-1.74), Model 1 (OR 1.57, 95% CI 1.38-1.80) and Model 2 (OR 1.45, 95% CI 1.27-1.65). In the unadjusted model, individuals in the highest quartile of cadmium level had a significantly increased risk of OSA symptoms of 53% (OR = 1.53, 95% CI: 1.42, 1.65) compared with participants in the bottom quartile, and this risk increased by 35% (OR = 1.35, 95% CI: 1.23, 1.48) after adjusting for all covariates. Individuals in the highest quartile of cadmium level were 76% more likely to have a trouble sleeping than individuals in the lowest quartile in the unadjusted model (OR = 1.76, 95% CI: 1.31, 1.93), whereas in the fully adjusted model, this likelihood was 86% higher (OR = 1.86, 95% CI: 1.51, 1.96). A similar positive correlation was also observed for cadmium level and daytime sleepiness. However, no relationship was noted between cadmium and excessive sleep duration (≥9 h). A linear dose-response relationship was found between cadmium concentration and the risk of insufficient sleeping (P non-linearity = 0.321), OSA symptoms (P non-linearity = 0.176), trouble sleeping (P non-linearity = 0.682) and daytime sleepiness (P non-linearity = 0.565). Additionally, no significant interactions between cadmium concentrations and subgroup variables were identified (P for interaction>0.05). Insufficient sleep, symptoms of OSA, trouble sleeping and daytime sleepiness were found to have a positive association with the blood cadmium concentration in US adults. However, further prospective studies are necessary to establish whether there is a causal relationship between these factors.

Cardiomyopathy: pathogenesis and therapeutic interventions.

Cardiomyopathy is a group of disease characterized by structural and functional damage to the myocardium. The etiologies of cardiomyopathies are diverse, spanning from genetic mutations impacting fundamental myocardial functions to systemic disorders that result in widespread cardiac damage. Many specific gene mutations cause primary cardiomyopathy. Environmental factors and metabolic disorders may also lead to the occurrence of cardiomyopathy. This review provides an in-depth analysis of the current understanding of the pathogenesis of various cardiomyopathies, highlighting the molecular and cellular mechanisms that contribute to their development and progression. The current therapeutic interventions for cardiomyopathies range from pharmacological interventions to mechanical support and heart transplantation. Gene therapy and cell therapy, propelled by ongoing advancements in overarching strategies and methodologies, has also emerged as a pivotal clinical intervention for a variety of diseases. The increasing number of causal gene of cardiomyopathies have been identified in recent studies. Therefore, gene therapy targeting causal genes holds promise in offering therapeutic advantages to individuals diagnosed with cardiomyopathies. Acting as a more precise approach to gene therapy, they are gradually emerging as a substitute for traditional gene therapy. This article reviews pathogenesis and therapeutic interventions for different cardiomyopathies.

Dynamics of clinical and immunological parameters in retinal pigment epithelium transplantation in the context of combined immunosuppressive therapy in the rabbit model of retinal degeneration

Progressive damage of the retinal pigment epithelium (RPE) underlies the pathogenesis of degenerative retinal diseases such as: age-related macular degeneration (AMD), Stargardt’s disease, retinitis pigmentosa, Best’s disease and others. This group of diseases led by AMD leads to irreversible loss of visual functions, blindness and disability. The possibilities of therapy of late stages of AMD are extremely limited. The most promising approach to replace the damaged retinal pigment epithelium appears to be transplantation of RPE cells derived from induced pluripotent stem cells (iPSC-RPE) into the subretinal space (SRS). Despite immune privilege in the SRS, transplantation of xenogeneic cellular material causes severe inflammation in the posterior segment of the eye and leads to graft rejection in an in vivo experiment in the absence of immunosuppression. The solution to the problem of tissue incompatibility in this case can be the use of combined immunosuppressive therapy (CIT), aimed, on the one hand, at suppression of local inflammation (in the eye) and, on the other hand, at suppression of the systemic transplantation immune response. The aim of the study: clinical and immunological analysis of the results of transplantation of IPSC-RPE suspension on the background of CIT, including single intravitreal intraoperative administration of kenalog and further systemic application of mycophenolate mofetil (MMF), in the model of RPE atrophy in rabbits. Standard and specialized ophthalmological examination was performed at early and distant terms after the intervention in order to clinically assess the posttransplantation process. To analyze the immune status, vitreous humor (VH) and blood serum (BS) of rabbits of the experimental groups were collected. The concentrations of TGF-β1, TGF-β2, and IL-2 were determined in the biomaterial using solid-phase enzyme immunoassay. According to the results of the study, subretinal transplantation of IPSC-RPE, performed against the background of combination of single intravitreal intraoperative administration of kenalog and systemic application of MMF, is a safe method, which provides preservation of the retina and other adjacent structures of the eye and allows to prevent rejection of xenogenic material during its transplantation both in a healthy eye and with pre-formed RPE atrophy, which opens perspectives for full testing of biological effects realized by IPSC-RPE.

Impact of Body Mass Index on Outcomes in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Single-Center Retrospective Study.

Pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) face several risk factors influencing transplantation success, including nutritional status as measured by body mass index (BMI). This study analyzed BMI data collected from patients transplanted between 2003 and 2023, and aimed to evaluate whether deviations from normal BMI are associated with poorer clinical outcomes. BMI levels assessed before and after first-line treatment and pre-transplantation were analyzed retrospectively to determine a correlation with survival and post-transplant complications. Underweight patients had significantly lower 12- and 36-month overall survival rates compared to normal-weight and overweight patients (p = 1.22 × 10-8 and p = 8.88 × 10-8, respectively). Event-free survival was also lower for underweight patients at all time points. A higher pre-transplant BMI increases the risk of acute graft-versus-host disease (GVHD, p = 0.00068). Otherwise, pre-transplant BMI was not significantly correlated with early TRCs and cGVHD. As secondary objectives, this study identified differences in BMI across primary disease groups, with solid tumor patients having the highest BMI and myelodysplastic syndrome patients having the lowest. BMI cut-offs were identified to predict or protect against serious outcomes, including delayed engraftment, TRCs, and acute and chronic GVHD. This study highlights the importance of nutritional assessment and management in pediatric patients undergoing allo-HSCT to optimize post-transplant outcomes, as deviations from a normal BMI can significantly impact post-transplant health. These findings underscore the importance of integrating BMI assessment throughout the entire pre-HSCT therapeutic course to identify patients at higher risk for complications and to define more effective nutritional management strategies.

Contemporary issues of the birth trauma

Background. Birth trauma is a group of diseases caused by mechanical factors during childbirth. Birth trauma is an interdisciplinary problem, affecting various fields of medicine, such as obstetrics, pediatrics, child neurology and other sciences. Birth trauma occupies an important place in the structure of perinatal morbidity and mortality. Birth injuries of newborns during vaginal birth occur in 3.6% of cases, during cesarean section — in 1.2%. However, at present, despite a comprehensive study of the problem, the incidence of birth trauma in newborns remains high. Along with obstetric birth trauma, spontaneous birth trauma also occurs — not associated with any obstetric care.Purpose of review. To summarize and analyze the available data on the causes of birth trauma in newborns depending on the type of birth injury.Materials and methods. The review includes published data over the past 10 years regarding the study of the causes of the main types of birth injuries in newborns. The literature search was conducted in Web of Science, Google Scholar, PubMed, and ELibrary databases.Results. The problem of fetal-pelvic disproportion in the genesis of the development of risk factors for maternal-fetal trauma remains relevant. Fetal macrosomia is one of the most significant factors in birth trauma. The most common skull injury in newborns is cephalohematoma. According to the mechanism of occurrence, birth trauma is divided into spontaneous — occurring during physiological childbirth — and obstetric — associated with any obstetric benefits. The degree of configuration of the fetal head plays a significant role in the pathogenesis of birth trauma. Birth trauma is considered as a systemic reaction on the part of the newborn’s body, which leads to a breakdown of compensatory and adaptive mechanisms and the development of critical damage to the central nervous system and is differentiated from birth damage, which includes only local changes.Conclusion. To search for preventive measures aimed at preventing birth injuries in newborns, it is necessary to systematize the groups of causes that influence the increased risk of birth injury. Timely assessment of the pathological configuration of the fetal head is extremely important when deciding on the advisability of using obstetric aids during vaginal operative delivery, since it is an early predictor of the formation of fetal-pelvic disproportion — a significant factor in birth trauma in the newborn. In recent years, taking into account the active study of molecular genetic mechanisms in the genesis of the formation of various pathological conditions, the search for various genetic and epigenetic factors that influence the risk of developing birth traumatic injuries in a newborn against the background of individual susceptibility to the effects of any physical factors during childbirth.

Evaluating MCMC Convergence in a Bayesian Model of ST-Elevation Myocardial Infarction Female Patients in Malaysia

The majority of research that looked at the Bayesian Markov Chain Monte Carlo (MCMC) approach for prognostic modelling of cardiovascular disease only focused on the use of the Bayesian approach in variable selection, model selection, and prior distribution selection. But very few of this research has looked at the Markov chains' convergence in the model. In this study, convergence diagnostics were carried out to evaluate the convergence of Markov chains using both visual inspection and additional diagnostics. The National Cardiovascular Disease Database-Acute Coronary Syndrome (NCVD-ACS) registry, which included 1248 female patients with ST-Elevation Myocardial Infarction (STEMI) between 2006 and 2013, was used for this study's analysis. The multivariate Bayesian model identified six significant variables: dyslipidaemia, myocardial infarction, smoking, renal disease, Killip class, and age group. The trace plots did not reveal any distinctive patterns based on these significant variables, and the model's MCMC mixing is typically good. While for the autocorrelation plots, mild autocorrelations for age group, Killip IV, as well as the intercept term in the model. Since there were only mild autocorrelations, no thinning is needed. Also, the Geweke diagnostic showed that the chain is divided into two windows containing a set fraction of the first and last iterations which produced standard Z-scores. The Geweke diagnostic did not provide evidence of non-convergence, as none of the Z-scores fell in the extreme tails of the N (0,1). In this study, a number of plots and additional diagnostic tools showed that the Markov chains have reached convergence, which is relevant to the general use of the MCMC approach.

Alleviating effect of whey protein supplementation on oxidative stress in hypothyroidism.

Hypothyroidism is one of the most prevalent thyroid pathologies, which causes oxidative stress by disrupting antioxidant mechanisms. In mammals, the thyroid glands regulate metabolism, development, and growth. Dysfunction of the thyroid gland can result in hypothyroidism, hyperthyroidism, thyroiditis, and thyroid cancer. Whey protein is a widely consumed protein supplement containing abundant sulphur-containing amino acids and bioactive peptides. Here, we analysed the effect of whey protein on oxidative stress in hypothyroidism. In vivo studies were conducted in two phases for 30 and 90 days, respectively. Hypothyroidism was induced in Wistar albino rats by administering 0.05% propylthiouracil (PTU) through drinking water. Five hypothyroid groups and the normal control group were maintained in the first 30 day phase of the study. Among these, one group served as the induced control group, three groups received whey protein at different concentrations (100, 300, and 500 mg per kg body weight), and the last group received L-thyroxine (2 μg per 100 g body weight) as a positive medication. The activities of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, were analysed, and the levels of total antioxidants, glutathione, and malondialdehyde were determined. Ca2+ ATPase and Na+/K+ ATPase activities were detected by estimating the inorganic phosphate content. Histopathological analysis was carried out on the thyroid and liver tissues of all groups. Antioxidant activity was notably increased for higher doses of whey protein compared to that in the diseased control group (p < 0.05). From this initial study, the dose that achieved the desired therapeutic effect was 500 mg kg-1, which was considered for the next 90 day phase of the study. The 90 day phase of the study was conducted with five groups: normal, whey protein-supplemented, hypothyroid, whey protein-supplemented hypothyroid, and levothyroxine-supplemented hypothyroid. All the PTU-treated groups showed degenerative alterations in thyroid histology. Whey protein supplementation causes a considerable decrease in MDA levels with an increase in the major antioxidant enzyme and ATPase activities, with p < 0.05. As a nutritional supplement, whey protein, at a 500 mg kg-1 dose, effectively boosts antioxidant activity without causing any toxicological concerns in long-term use.

The influence of telehealth-based interventions in patients with cancer in the digital era of society 5.0: A literature review

Background: Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells, which can result in death if not managed. It is important for cancer patients to be able to participate in long-term treatment programs. Therefore, a good support system, healthcare professionals' support, and the utilization of information technology in healthcare services are needed. The management of cancer is also expected to adapt to the era of Society 5.0. The use of Telehealth has been recommended by the World Health Organization (WHO) to support current healthcare services. The implementation of the combination of telehealth is expected to be a solution for holistic cancer care in the digital era. Purpose: To explore the effectiveness of telehealth-based interventions on cancer patients in the digital era of society 5.0. Method: Literature review using online databases such as Sage Journals, Science Direct, Clinical Key Nursing, and PubMed. Inclusion criteria: articles on the application of telehealth for cancer patients, available in full text in English, published between 2020-2023. Exclusion criteria: articles published before 2020, articles that do not discuss telehealth in cancer patients, and literature review studies. Results: Analysis of the 13 articles used shows the important role of combining telehealth (telenursing, telepalliative, telerehabilitation, teleoncology), which is beneficial not only for cancer patients but also for nurses and other healthcare professionals in providing good quality, safe, effective, and efficient healthcare services in the digital era of society 5.0. Conclusion: Telehealth-based cancer rehabilitation demonstrates a positive impact that warrants further evaluation and study.

Prognostic Nutrition Index as a Biomarker for Treatment Sensitivity to Chemotherapy and Nivolumab as the First-Line Treatment in Patients with Unresectable Advanced or Recurrent Gastric Cancer: A Multicenter Study

Introduction: This multicenter study aimed to determine whether the pretreatment prognostic nutrition index (PNI) or a change in the index after two treatment courses could be a biomarker for predicting treatment sensitivity in patients with unresectable advanced or recurrent gastric cancer (GC) treated using chemotherapy and nivolumab as the first-line treatment. Methods: This multicenter retrospective study with 104 patients was conducted at 12 institutions. PNI was calculated before treatment and after two courses of treatment in each case. We also focused on changes in PNI from the pretreatment value. Results: After two courses of chemotherapy plus nivolumab treatment, the high PNI group had significantly better rates of overall survival (OS) (p = 0.0016) and time to treatment failure (p = 0.0060). Low PNI was an independent prognostic factor predicting both therapeutic sensitivity to chemotherapy plus nivolumab treatment and poorer OS. Furthermore, correlation with low pretreatment PNI transitioning to high after two courses of treatment was not noted in any patient in the progressive disease group (p = 0.0075). Conclusions: PNI is a score composed of a patient’s albumin level and lymphocyte count that can be easily assessed in daily clinical practice. Evaluating it is easy for each treatment; thus, when there is a focus on its transition, PNI could be a very powerful biomarker for predicting treatment sensitivity.

Association between varicose veins and constitution of traditional Chinese medicine plus heart-failure-like symptoms.

Varicose veins are a common issue for employees in jobs that require prolonged standing compared with all other employees. However, its relationship with presentations of traditional Chinese medicine constitution is unknown. This study aimed to investigate their association. Data in the study were obtained from questionnaires of patients in Taiwan Biobank, enrolled from 2008 to 2020. The responses to the statement "I can see distorted blood vessels on my four limbs (varicose veins)." were categorized into none, mild, moderate, severe. and more severe, and the same scale was also used to classify breathing difficulties and hypotension. A total of 11,293 participants were enrolled in the study. The prevalence of women was higher in the studied group compared with the control. Patients complained of breathing difficulties with moderate (30.49%) and severe discomfort (12.44%) in the diseased group. Regarding hypotension, 28.81% and 9.82% of the patients presented with moderate and severe hypotension, respectively. The cofactor odds ratio was 1.775 for severe breathing difficulty/moderate hypotension and 2.235 for severe breathing difficulty/severe hypotension, with statistical significance. The combined impact of breathing difficulties and hypotension increased with severity. Varicose veins had a higher association with breathing difficulties and hypotension as the severity of the condition worsened. The combined impact of breathing difficulties and hypotension increased as the disease progressed. Therefore, self-reported assessments can be a useful tool for evaluating patients with asymptomatic varicose veins before the development of "heart-failure-like symptoms" to reduce the risk of underdiagnosis.

Hereditary Aortopathies as Cause of Sudden Cardiac Death in the Young: State-of-the-Art Review in Molecular Medicine

Hereditary aortopathies are a group of rare genetic diseases affecting the aorta and its major branches, and they represent a cause of sudden cardiac death. These pathologies are classified into syndromic hereditary aortopathies and non-syndromic hereditary aortopathies. The epidemiology of hereditary aortopathies varies according to the specific genetic condition involved; however, these disorders are believed to account for a significant proportion of sudden cardiac death in young individuals with a family history of inherited cardiovascular conditions. The causes of hereditary aortopathies are primarily genetic, with pathogenic variants in various genes encoding structural proteins of the vascular wall, leading to dissection, aneurysms, rupture, and ultimately sudden cardiac death. When the cause of death remains unknown after an autopsy, it is referred to as sudden unexplained death, and post-mortem genetic testing, known as a molecular autopsy, is crucial to confirm hereditary aortopathies and assess the genetic risk in the patient’s relatives. This helps to facilitate diagnostic and therapeutic pathways and/or implement monitoring strategies to prevent sudden cardiac death. In this state-of-the-art review, we focus on syndromic and non-syndromic hereditary aortopathies causing sudden cardiac death in the young and explore preventive strategies for affected family members.

Autoantibody against aquaporin-5 may be a new diagnostic biomarker for primary Sjögren's syndrome.

The study aims to assess the diagnostic and clinical significance of autoantibodies against aquaporin-1 (anti-AQP1) and aquaporin-5 (anti-AQP5) in primary Sjögren's syndrome (pSS). A total of 163 participants were categorized into three groups: pSS group, other connective tissue diseases (CTD) group, and healthy control (HC) group. The levels of anti-AQP1 and anti-AQP5 autoantibodies in serum were determined using enzyme-linked immunosorbent assay (ELISA), and clinical data from patients were collected for statistical analysis. Our results showed that the level of anti-AQP1 in the pSS group was higher than in the HC group (P < 0.05), and no significant difference was observed between the pSS group and the CTD group (P > 0.05). ROC showed that the anti-AQP1 had no diagnostic value for pSS (P > 0.05). The anti-AQP5 level of 39 healthy adults was all below the cut-off value (14.10ng/ml) (P < 0.05). The level of anti-AQP5 in the pSS group was higher than the CTD group (P < 0.05), the AUC was 0.86 (95% CI 0.80-0.93), with a sensitivity of 0.95 (95% CI 0.87-0.99) and a specificity of 0.70 (95% CI 0.58-0.84). No correlation was found between anti-AQP5 levels and the EULAR primary Sjögren's syndrome disease activity index score, anti-SSA, anti-SSB, antinuclear antibodies, rheumatoid factor, anti-ds-DNA, salivary gland flow rate, complement 3, and lymphocyte count in pSS samples (P > 0.05), respectively. Therefore, the elevated anti-AQP5 may emerge as a novel diagnostic biomarker for pSS patients due to high sensitivity and specificity.

Expression of AQP8 in Serum of Patients With Meniere's Disease and Its Value in Evaluating the Degree of Hydrolabyrinth and Predicting Prognosis.

This study aims to explore the role of serum aquaporin 8 (AQP8) expression in evaluating the degree of hydrolabyrinth and predicting prognosis in patients with Meniere's disease. One hundred and five patients diagnosed with Meniere's disease in our hospital were enrolled in the Meniere's disease group. Another 102 healthy subjects were enrolled as the control group. The expression of serum AQP8 mRNA was determined by the quantitative real-time PCR (qRT-PCR) method. Receiver operating characteristic (ROC) curve analysis was carried out to analyse the predictive value of serum AQP8 mRNA expression for poor prognosis in Meniere's disease patients. Multivariate logistic regression was used to analyse the influencing factors of poor prognosis in patients with Meniere's disease. The expression level of serum AQP8 mRNA in the Meniere's disease group was significantly higher than that in the control group (p < 0.05). In the severe hydrops group, serum AQP8 mRNA expression levels were higher than in the mild hydrops group and the no endolymphatic hydrops group. Additionally, the mild hydrops group had higher serum AQP8 mRNA levels than the no endolymphatic hydrops group (p < 0.05). The disease course, proportion of severe hydrops and serum AQP8 mRNA expression were all higher in the poor prognosis group compared to the good prognosis group (p < 0.05). The area under the curve (AUC) for serum AQP8 mRNA in predicting poor prognosis in Meniere's disease patients was 0.812 (95%CI: 0.702-0.922). AQP8 mRNA is associated with the degree of hydrolabyrinth in patients with Meniere's disease and plays an important role in predicting prognosis.

Neimann-Pick Diseases: Beyond Lipid Accumulation – Genetic, Diagnostics, and Therapeutic Strategies

Rare genetic disorders are the group of disorders/diseases that occur in such a low count that they are not considered much active market for therapeutics unless encouraged by appropriate incentives and support. They are too rare to be fully investigated and managed by health professionals. Genetic disorders are caused by change in genes and are often serious and complex. Around the world, most affected individuals are found to be children. They can be progressive and might get worse as children grow older. Niemann-Pick diseases (NPD) is one such group of rare genetic diseases that are characterized by unwanted and abnormal accumulation of lipids within the cells. In this review, we discuss the history, genetic basis, clinical manifestations and diagnostic approaches for NPD. We further discuss the pathophysiology of accumulation of lipids and their impact on cellular functions and organ systems and various management strategies.Keywords: Rare disease; Genetic mutation; Lipid metabolism; Cholesterol trafficking; Neurological abnormalities