Reviews of physiology, biochemistry and pharmacologyUndurti N Das
The human brain is rich in AA and DHA, which are crucial for normal brain growth and development and memory. They form a major structural component of neurons of the cerebral cortex and photoreceptor cells in the retina. AA and DHA support synaptic plasticity and contribute to efficient neurotransmission. Adequate amounts of AA and DHA support neuronal growth and the formation of new synapses and thus are crucial for memory and cognitive function.Depression, anxiety, schizophrenia, and other neurological diseases occur more frequently in those with coronary heart disease (CHD) and vice versa. Transient depression and anxious mood can trigger acute cardiac events and fatal arrhythmias. Serotonin and catecholamines play a significant role in depression and anxiety and are known to activate platelets, which increases the risk of cardiovascular events. Both serotonin and catecholamines modulate inflammation, while levels of pro-inflammatory cytokines are elevated in anxiety and depression and other psychiatric conditions and CHD. Depression, anxiety, and CHD involve altered essential fatty acid metabolism, particularly of AA and DHA, whose metabolites can inhibit platelet activation, suppress inflammation, and enhance acetylcholine levels. Acetylcholine, in turn, regulates the concentrations of serotonin and catecholamines. Acetylcholine and catecholamines have a modulatory influence on inflammation. Exercise is anti-inflammatory in nature, by virtue of its ability to enhance the formation of anti-inflammatory lipoxin A4, resolvins, protectin, and maresins and suppress pro-inflammatory cytokines IL-6 and TNF-α. AA and DHA enhance acetylcholine release and augment the formation of endothelial nitric oxide (NO). These results imply that anxiety, depression, and CHD are low-grade systemic inflammatory conditions that could benefit from the administration of appropriate amounts of AA and DHA. Risk factors for CHD such as obesity, type 2 diabetes mellitus, dyslipidemia, and atherosclerosis are all considered pro-inflammatory conditions.Since both neuropsychiatric conditions and recovery from CHD need the generation of new neurons and myocardial cells respectively that need to get integrated to the existing cells/tissues, it is proposed that a combination of brain-derived neurotrophic factor (BDNF) (that is needed for neuronal cells to survive), growth hormone (GH) (needed for growth of the newly generated neurons and myocardial cells), resolvins/lipoxins/protectins/maresins (needed to suppress inflammation and enhance wound healing), retinoic acid (needed for vertebrate development), and 1,4-DPCA that inhibits the excessive deposition of collagen and an inducer of formation of new blood vessels (angiogenesis) may be of significant benefit both in the prevention and management of neuropsychiatric conditions and CHD and their associated conditions such as obesity, diabetes mellitus, dyslipidemia, and atherosclerosis.
Reviews of physiology, biochemistry and pharmacologyUndurti N Das
Human essential hypertension is driven by a network of interacting nutritional, metabolic, inflammatory, and endothelial mechanisms in which AA and other PUFAs play a critical role. Beyond excess sodium intake, population data supports the role of inadequate calcium, potassium, and magnesium intake and low antioxidant vitamin status in shaping blood pressure regulation. These nutrients influence vascular smooth muscle tone and act as cofactors that support Δ6 and Δ5 desaturase activities, thereby governing tissue availability of AA, EPA, and DHA and downstream formation of vasodilator and antiplatelet mediators (e.g., PGE1, prostacyclin), as well as inflammation-resolving lipid mediators (lipoxins, resolvins, protectins, maresins, and nitrolipids).Endothelial dysfunction characterized by reduced endothelial nitric oxide (eNO) bioavailability and increased oxidative stress seems to play an important role in the pathobiology of HTN. High salt intake, asymmetric dimethylarginine (ADMA), and activation of NAD(P)H oxidase and angiotensin II signaling promote superoxide generation that quenches NO and shifts the vascular balance toward vasoconstriction. Clinical and experimental observations indicate that antihypertensive therapies can partly restore NO and antioxidant defenses, while dietary patterns rich in n-3 fatty acids (particularly DHA) and balanced n-6/n-3 intake may lower blood pressure by suppressing thromboxane formation and enhancing vasoprotective, pro-resolving pathways.Preeclampsia can be considered as a model of reversible hypertension linked to oxidative stress and angiogenic imbalance (sFlt1, soluble endoglin), highlighting mechanistic overlap with essential hypertension. Hypertension is a low-grade systemic inflammatory condition whose origins may be present in the perinatal period through long-term programming of PUFA metabolism and endothelial function.
Reviews of physiology, biochemistry and pharmacologyUndurti N Das
AA has several physiological functions. Its various metabolites also have many significant actions and thus participate in innumerable physiological and pathological processes. There is strong evidence to suggest that AA and its metabolites play a significant role in the pathophysiology of diabetes mellitus (DM), hypertension (HTN), and coronary heart disease. In addition, high-fat diet (HFD), high-cholesterol diet (HCD), calorie-dense foods (CDF), high-salt and low-potassium diet, low magnesium, lack of exercise, sedentary lifestyle, and aging alter the generation of AA from its dietary precursor linoleic acid (LA) by altering the activities of desaturases. This may enhance the occurrence of a pro-inflammatory milieu in the cells/tissues/organs that can be ameliorated to a certain extent by AA.
Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyD V Vankov, O V Obukhova, I A Deev, M A Ivanova
The diseases of circulatory system represent one of the main problems of the population health due to corresponding high morbidity and mortality and load on health care. The purpose of the study is to evaluate direct and indirect costs of medical care under acute coronary syndrome depending on level of medical organization. The study used content-analysis, statistical and analytical methods scientific publications on the research topic, copying of data from the medical documentation of the Vologda Regional Clinical Hospital for the period 2012-2021. The significant number of publications confirm that diseases of circulatory system develop due to multitude of risk factors. Also economic and medical effectiveness of timely applied medical care of diseases of the circulatory system is proved. It is demonstrated that medical care and cardiac rehabilitation under acute coronary syndrome are the most resource-wasteful types of medical care, while prevention of development of disease allows to save human, material and financial resources. In the medium perspective, economic damage under the worst scenario of development of disease when disability is set in makes up to about 400.000 rubles and in case of death of patient, more than five million rubles. Under acute coronary syndrome, medical, social and economic efficiency of emergency medical care is higher in medical organizations of the 3rd level. However, it is more economically advantageous to implement preventive measures.
Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyM V Botnaryuk, Y A Lepekhina
The sailors more often than other professional groups are forced to work in extreme conditions associated with heat, humidity and low temperatures (passage of tropical and northern latitudes). Therefore, they are at risk of development of various diseases and the most dangerous are cardiovascular ones. Despite taken protective measures, the number of crew members of merchant marine vessel complaining on poor well-being continues to increase, including at the expense of disorders of heart and vascular functioning. With purpose to enhance measures preventing development of cardiovascular diseases that currently are not always detected during pre-voyage medical examination and result in health deterioration and lethal outcomes, the article proposes a number of practical recommendations. It is relevant to carry out genetic examination before starting voyage in order to identify risks of development of occupational diseases in sailors older than 40 years. To equip vessel with portable cardiograph will contribute to timely detection of physiological changes in heart functioning of of crew member and will reduce possibility of occurrence of life-threatening conditions. The issuing of voluntary medical insurance program will permit to apply more in-depth diagnostics with purpose to increase possibility to detect cardiovascular diseases at early stage.
Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyA B Dzhanaliev, N K Kasiev, M Kulzhanov
The diseases of circulatory system continue to occupy leading positions in structure of morbidity and mortality of population, remaining one of key public health problems. The purpose of the study is to investigate dynamics of primary morbidity and prevalence of diseases of circulatory system by main nosological forms among adult and adolescent population of the Kyrgyz Republic in 2018-2024. The study used official data from the Center for E-Health Care that was analyzed using retrospective, statistical and comparative analytical methods. It was found that indicators of primary morbidity and prevalence were characterized by pronounced variability with greatest increase in 2022, against the background of decrease in 2020-2021, that may be due to changes in availability of medical care in period of COVID-19 pandemic. The highest levels of morbidity and prevalence were found for hypertension, coronary heart disease and cerebrovascular diseases. Some nosologies, including myocardial infarction and other peripheral vascular diseases, demonstrated sharp increase in indicators, suggesting changes in disease detection and health care seeking behavior of population. The obtained results confirm necessity to improve system of monitoring, prevention and early detection of cardiovascular diseases, especially among high-risk groups.
BACKGROUND: Cardiac arrest (CA) is associated with high mortality and severe neurological sequelae. Artemisinin (ARS), a natural product from Artemisia annua, has potential neuroprotective effects, but its role in brain injury after CA resuscitation remains unclear. OBJECTIVES: This study investigated the effects of ARS on hippocampal neuronal apoptosis and cognitive dysfunction in rats after CA resuscitation and explored whether these effects are associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. METHODS: Sixty male rats were randomly assigned to six groups: sham, model, artemisinin (40 mg/kg), dimethyl sulfoxide ((DMSO, 100 mg/kg), LY294002 (a phosphatidylinositol 3-kinase inhibitor, 25 mg/kg) and artemisinin plus LY294002. Cardiac arrest was induced by transcutaneous electrical stimulation. Outcome assessors were blinded. Neurological function was evaluated using the Neurological Deficit Scale. Hippocampal damage and apoptosis were assessed by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Learning and memory were tested using novel object recognition and the Morris water maze. Protein expression was measured by Western blot. RESULTS: Artemisinin significantly improved Neurological Deficit Scale scores, reduced terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and alleviated hippocampal damage. Artemisinin also prolonged novel object exploration time, shortened escape latency, increased target quadrant time and upregulated phosphatidylinositol 3-kinase expression and the ratio of phosphorylated protein kinase B to protein kinase B. Co-administration of LY294002 partially reversed these effects. CONCLUSION: Artemisinin alleviates hippocampal neuronal apoptosis and improves neurological deficits and cognitive dysfunction in rats after cardiac arrest resuscitation, suggesting a possible association with activation of the phosphatidylinositol 3-kinase/protein kinase B pathway. Limitations include use of a single pharmacological inhibitor and lack of genetic validation.
Journal of the peripheral nervous system : JPNSKryštof Prášil, Veronika Potočková, Tomáš Nedělka, Alžběta Prášilová, Radim Mazanec
BACKGROUND AND AIMS: Data on cardiovascular autonomic neuropathy (CAN) are sparse in Charcot-Marie-Tooth disease. We aimed to determine the prevalence of CAN in CMT1A and CMTX1 and its associations with neuropathy severity and heart rate variability (HRV), compared with age- and sex-matched controls. METHODS: Thirty-six CMT1A, 24 CMTX1 patients, and 62 controls underwent cardiovascular autonomic testing including the modified Ewing battery (Expiration: Inspiration ratio, 30:15 ratio, Valsalva ratio; complete in 41/62 controls), orthostatic blood pressure measurement, and HRV analysis from 10-min supine-standing recordings. Abnormality was defined using age-stratified 2.3rd-percentile cutoffs. CMT Neuropathy Score version 2 (CMTNSv2) and Survey of Autonomic Symptoms were recorded. Comparisons used Fisher's exact test and the Kruskal-Wallis test with Holm correction; HRV was age- and sex-adjusted. RESULTS: CAN was present in 30.6% of CMT1A and 33.3% of CMTX1, versus 10.0% of controls (p = 0.011). Definite CAN occurred only in CMT1A (11.1%), although the CMT1A-CMTX1 contrast was not significant (p = 0.14). The Valsalva ratio was lower in CMT1A than in CMTX1 (median 1.54 vs. 1.89, p = 0.001), with abnormal values confined to CMT1A (14.7%). After age and sex adjustment, vagal HRV was reduced in CMT1A but not CMTX1. INTERPRETATION: CAN affects approximately one-third of patients with CMT1A and CMTX1, roughly three times the control prevalence. Overall prevalence was similar in the two genotypes, but Valsalva impairment was confined to CMT1A, indicating that similar prevalence does not imply an identical pattern of involvement. Cardiovascular autonomic assessment warrants consideration in these patients, particularly perioperatively.
Journal of foot and ankle researchLevi Kadiri, Anthony Maher, Andy Bridgen
BACKGROUND: Diabetic foot osteomyelitis (DFO) is a serious complication of diabetic foot ulcers and is associated with increased risk of amputation, morbidity, and mortality. Bone biopsy remains the most definitive diagnostic modality, yet controversy persists over its diagnostic utility This study reviews the diagnostic concordance of histopathology and microbiology in bone biopsy specimens from patients with DFO and examines the clinical implications of the findings. METHODS: A systematic review was conducted using PubMed, Medline, CINHAL, Cochrane Library, and Google Scholar. Studies included adult patients with DFO in whom bone biopsy specimens underwent both histopathological and microbiological analysis. Five core studies met the eligibility criteria. Data on study design, setting, population, diagnostic methods, concordance rates, and outcomes were extracted and synthesized utilising a quantitative narrative synthesis. RESULTS: Across the five studies (n = 308 patients), histopathology and microbiology showed modest concordance, with mean rates of concordant positive results of 43.4% and common discordant findings. Histopathology demonstrated higher specificity, while microbiology had higher sensitivity, ranging from 70% to 83.9% but greater susceptibility to contamination. Positive histopathology was more strongly associated with the need for revision surgery or extended antibiotic therapy. DISCUSSION: Histopathology appears to offer superior diagnostic specificity, whereas microbiology provides valuable information for antimicrobial management. Frequent discordance underscores the importance of interpreting results in a clinical context. Further robust, prospective studies are needed to clarify the optimal diagnostic approach and standardise definitions.
This study aimed to validate the knowledge-attitude-practice (KAP) model in coronary heart disease (CHD) patients and their family caregivers, and examine the moderating role of dyadic care types. Data were collected from 281 patient-caregiver dyads, and moderated mediation models were constructed. In both patients and caregivers, knowledge and attitudes had significant direct effects on disease management practices, with attitudes partially mediating the knowledge-practice relationship. Among the four dyadic care types (patient-oriented, caregiver-oriented, collaborative, and incongruent), incongruent dyads showed a significantly stronger direct effect of patients' knowledge on their self-management practices (β = 0.94, 95% CI: 0.4, 1.49) than congruent configurations. Conversely, incongruent dyads significantly weakened the association between caregivers' knowledge and their health attitudes (β = -0.32, 95% CI: -0.60, -0.03), and reduced the impact of caregivers' knowledge on caregiving practices (β = -0.99, 95% CI: -1.53, -0.44). These findings emphasize the need for tailored health education and interventions based on specific dyadic interaction types.
Vascular dementia (VaD), caused by reduced cerebral blood flow, is a common form of dementia lacking effective treatments. This study used genome-wide association study (GWAS) summary data, Mendelian randomization (MR), and colocalization analyzes to prioritize blood metabolites and candidate therapeutic targets associated with VaD. Key analyzes included metabolic pathway enrichment, a descriptive Phenome-Wide Association Study (PheWAS) of the broader curated association profiles of prioritized genes, mediation analysis, and in-silico compound prioritization with molecular docking. Twenty-four metabolites were associated with VaD, with taurocholate and glutaroyl carnitine prioritized as tier 1 metabolite-gene pairs. Pathway analysis implicated aminoacyl-tRNA and branched-chain amino acid biosynthesis pathways. Apolipoprotein E (APOE) and glutaryl-CoA dehydrogenase (GCDH) were prioritized candidate genes. The PheWAS recapitulated APOE's curated associations with Alzheimer's disease and lipid traits, whereas GCDH had a more restricted curated association profile dominated by glutaric acidemia type I; these patterns provide pleiotropic context but do not establish safety. Single-cell RNA-sequencing analysis localized APOE predominantly to microglia and astrocytes and GCDH predominantly to oligodendrocytes, providing cell-type-specific context. Mediation analysis identified a statistically supported indirect pathway involving alpha-2-macroglobulin receptor-associated protein for taurocholate. Aflatoxin B1 was highly ranked in an in-silico query but, because of its established toxicity, is not a therapeutic candidate. This study prioritizes metabolic and genetic candidates for experimental and clinical follow-up rather than establishing therapeutic targets.
Pakistan journal of pharmaceutical sciencesZhongshu Han, Ping Zhu
BACKGROUND: Diabetes retinopathy (DR) is the main blinding complication of type 2 diabetes (T2DM). Glycated hemoglobin (HbA1c) can reflect long-term blood glucose control and optical coherence tomography (OCT) can evaluate retinal microvessels. The effects of metformin and insulin regimens on microvascular structure are not yet clear. OBJECTIVES: To explore the relationship between HbA1c levels and retinal microvascular changes in T2DM patients receiving metformin and/or insulin and to evaluate the impact of different hypoglycemic regimens on DR progression. METHODS: This retrospective study included T2DM patients with non‑proliferative DR treated between January 2023 and December 2024. After propensity score matching (PSM), 31 patients per group received metformin monotherapy (M), insulin‑based therapy (Ins), or combined therapy (M‑Ins). HbA1c, HbA1c variability (HbA1c‑SD), DR grade, central macular thickness (CMT), retinal nerve fiber layer (RNFL) thickness and superficial/deep capillary plexus (SCP/DCP) density were recorded at baseline, 1‑ and 2‑year follow‑up. Multiple linear regression and Cox regression were used. RESULTS: After 2 years, HbA1c and HbA1c‑SD decreased significantly in all groups (p<0.05), with greater reduction in the M‑Ins group. DR progression was documented in 23 patients (24.7%), with rates of 16.1%, 38.7% and 19.4% in the M, Ins and M-Ins groups, respectively (p>0.05). OCT showed reduced CMT/RNFL and increased SCP/DCP density in all groups (p<0.05), with better improvement in M‑Ins group (p<0.05). HbA1c correlated positively with CMT/RNFL and negatively with SCP/DCP (p<0.05). Cox regression indicated that higher HbA1c-SD was an independent risk factor for DR progression (HR = 3.216, 95% CI: 1.011-10.230, p= 0.048), while metformin use was an independent protective factor (HR=0.694, 95% CI: 0.451-0.840, p=0.001). CONCLUSION: Metformin plus insulin was associated with greater HbA1c reduction, decreased glycemic variability and increased retinal vessel density and may thus slow DR progression. Both HbA1c-SD and SCP density were correlated with DR progression risk, supporting the combined use of glycemic variability and OCT parameters for clinical evaluation and treatment guidance.
Australasian journal on ageingIsabella Tan, Aletta E Schutte, Catherine Morgan, Henry Brodaty, Sonali R Gnanenthiran, Katya Numbers, Hueiming Liu, Menglu Ouyang, Paola Incerti, Padraig Kitt…
OBJECTIVE: To determine the potential feasibility and acceptability of combined screening for raised blood pressure (BP), atrial fibrillation (AF) and cognitive impairment (CI) in older adults within a setting of hearing health assessment for detection of hearing loss. METHODS: We recruited participants aged 65 years or older (n = 35; mean age 73 ± 6 years, 51% females) from the community to attend a single visit lasting approximately 60-90 min. Prior to a comprehensive hearing assessment, BP was measured with an automatic BP monitor with AF detection, and CI screening was conducted using the patient section of the General Practitioner Assessment of Cognition instrument. A subset of participants (n = 16, 50% females) was interviewed post study to evaluate acceptability. RESULTS: A total of 21 positive screens (six raised BP; two possible AF; 13 hearing loss) and 12 potential positive screens for possible CI were detected in 25 (71%) participants. Eight participants (23%) had more than one newly detected condition. Interviews revealed that combined screening was feasible and acceptable as participants felt it was 'convenient,' 'saves time' and 'more efficient.' CONCLUSIONS: Combined screening for raised BP, AF and CI in older adults within a hearing health assessment setting appears feasible and was generally perceived positively by participants in this pilot study. Further implementation studies should be conducted with process and outcome evaluation embedded to confirm feasibility and acceptability as well as to evaluate cost-effectiveness and health outcomes for combined screening in older adults.
GliaWei Kong, Hui Li, Zhou Wu, Yoshinori Hayashi, Hiroshi Nakanishi, Juan Zhao, Yutong Zhang, Hong Qing, Zhenzhen Quan, Junjun Ni
Neuroimmune responses critically shape the progression and outcome of ischemic stroke, yet the cell type-specific roles of myeloid populations remain incompletely defined. Cathepsin B (CatB), a lysosomal cysteine protease, has been implicated in neuroinflammation, but its contribution from distinct myeloid subsets is unclear. Transient middle cerebral artery occlusion (tMCAO) was induced in wild-type and CatB-deficient mice. Bone marrow chimeras were generated to selectively delete CatB in peripheral myeloid cells or resident microglia. Infarct severity, mortality, myeloid phenotypes, and transcriptional programs were assessed using flow cytometry, immunofluorescence, and bulk and cell type-resolved RNA sequencing. CatB expression was markedly upregulated in ischemic brain myeloid cells, with higher levels in infiltrating macrophages than in microglia. Selective deletion of CatB in peripheral myeloid cells, but not in microglia, significantly reduced infarct size, mortality, and pro-inflammatory gene expression after tMCAO. Transcriptomic analyses showed suppression of inflammatory pathways and preservation of neuronal signaling in mice lacking macrophage-derived CatB. Cell type-resolved RNA sequencing revealed that CatB deficiency shifted infiltrating macrophages toward a pro-resolving, tissue-repair phenotype characterized by increased expression of M2-associated genes, including Chil3. Consistently, CatB-deficient macrophages displayed enhanced pro-resolving polarization in response to ischemic neuron-derived signals in vitro. CatB was also elevated in circulating Ly6C+ monocytes after stroke. These findings identify peripheral myeloid-derived CatB as a key driver of ischemic brain injury and a potential therapeutic target.
BACKGROUND: In aspirin-treated unstable angina (UA), heterogeneity in on-treatment arachidonic acid (AA)-induced platelet aggregation and cholesterol reduction contributes to residual ischemic risk. Insomnia is prevalent in coronary disease, yet its association with specific aspirin-sensitive platelet aggregation kinetics and lipid parameters remains undefined. METHODS: In a cross-sectional cohort of 198 aspirin-treated UA patients, 38 routine hematologic or biochemical variables including AA-induced platelet aggregation indices were analyzed using principal component analysis (PCA) and unsupervised phenotyping (k-means and hierarchical clustering). Elastic-net logistic regression and machine learning classifiers were used for multivariable modeling, and performance was estimated by cross-validation. Correlation-network analysis and Shapley additive explanations (SHAP) supported interpretability. RESULTS: Unsupervised analyses consistently identified two phenotypes. Insomnia was enriched in a platelet-lipid phenotype characterized by lower platelet aggregation indices and a lower lipid marker profile. The K-nearest neighbors (KNN) model demonstrated strong cross-validated discrimination (AUC = 0.934; average precision = 0.923), while all four classifiers converged with AUC > 0.925. After age matching, elastic-net logistic regression retained only AA-induced maximal platelet aggregation (PmaxAggR) and total cholesterol (CHOL) as independent predictors, with odds ratios of 0.927 and 0.340, respectively (both p < .001). Inflammatory markers, including neutrophil count and monocyte count, were no longer selected. Network analysis placed insomnia within the platelet-lipid module linked to PMaxAggR, CHOL, and some other platelet or lipid indices. CONCLUSIONS: In age-matched, aspirin-treated UA patients, insomnia is independently associated with reduced PMaxAggR and lower CHOL, with inflammatory markers no longer significant after age-balancing. These findings delineate an age-independent platelet-cholesterol axis linked to insomnia, potentially reflecting shared autonomic and neurobiological dysregulation, and motivate sleep evaluation as part of platelet-reactivity phenotyping in this population.
Annals of medicineHui Cheng, Jiaheng Chen, Yu Ting Li, Tai Weng, Yao Jie Xie, Jose Hernandez, Wenyong Huang, Harry H X Wang
BACKGROUND: Despite optimal low-density lipoprotein cholesterol (LDL-C) management, residual vascular risk remains high in patients with type 2 diabetes (T2D). Remnant cholesterol (RC) is an atherogenic lipid fraction, yet its longitudinal association with diabetic retinopathy (DR) remains insufficiently characterised. We aimed to evaluate whether longitudinal RC measurements independently predict new-onset DR. MATERIALS AND METHODS: We recruited 1,580 Chinese adults with T2D and no DR from a community-based prospective cohort established between 2017 and 2019. Participants were followed annually until 2023. Association between RC and incident DR was evaluated using time-dependent Cox regression models. We specifically examined this association among participants who achieved clinical targets for conventional lipid panel. RESULTS: We observed 304 incident DR cases during five follow-up visits. Each one-unit increase in natural log-transformed RC was associated with a 26% higher risk of new-onset DR (adjusted hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.08-1.47). Elevated RC (≥0.8 mmol/L) was associated with a 50% increased DR risk (aHR 1.50, 95% CI 1.11-2.03). These associations persisted among participants meeting guideline-recommended targets for triglycerides, LDL-C, and high-density lipoprotein cholesterol. Such associations were more prominent in women and patients with longer duration of T2D (p for interaction <0.05). CONCLUSIONS: Elevated RC is an independent risk factor for new-onset DR and represents an important contributor to residual risk in patients with otherwise optimal lipid profiles. These findings suggest that RC merits consideration for integration into routine metabolic monitoring to improve DR risk stratification, particularly among female patients and those with long-standing diabetes.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyKübra Kurt Bilirer, Hale Özer Çaltek, Barış Boza, Selvi Aydın Şenel, Hamdullah Pekkolay, Mehmet Gümüştaş
BACKGROUND: Foetal situs abnormalities, including situs inversus totalis (SIT), right atrial isomerism (RAI) and left atrial isomerism (LAI), are associated with substantial variation in cardiac anatomy and postnatal outcomes. This study aimed to compare prenatal characteristics, associated abnormalities, perinatal outcomes, postnatal management and survival among foetuses with SIT, RAI and LAI. METHODS: This retrospective cohort study included 73 foetuses prenatally diagnosed with SIT (n = 12), RAI (n = 24) or LAI (n = 37) at a tertiary foetal cardiology and perinatology centre between 2021 and 2025. Prenatal cardiac and extracardiac findings, pregnancy and neonatal outcomes, postnatal surgical management pathways, and survival were evaluated. Survival was assessed using Kaplan-Meier's analysis, and factors associated with 1-year mortality were examined using Cox proportional hazards regression. RESULTS: Cardiac phenotypes differed significantly among groups. Interrupted inferior vena cava (IVC) occurred predominantly in LAI, whereas aortic-IVC juxtaposition, double-outlet right ventricle, anomalous pulmonary venous return and unbalanced atrioventricular septal defect were more frequent in RAI. Arrhythmias occurred exclusively in LAI. Postnatal surgical management pathways differed significantly among groups (p = 0.001), with univentricular pathway most frequent in RAI. Survival distributions did not differ significantly among SIT, RAI and LAI (log-rank p = 0.193). Exploratory multivariable analysis showed an association between right ventricular outflow tract obstruction (RVOTO) and increased 1-year mortality (HR 4.79, 95% CI 1.51-15.10; p = 0.008). CONCLUSIONS: Prenatally diagnosed SIT, RAI and LAI demonstrate distinct cardiac phenotypes and postnatal management requirements. Prognosis appears to depend not only on the laterality phenotype but also on specific cardiac morphology, with RVOTO emerging as an important prognostic marker. Detailed segmental foetal echocardiography may improve prenatal risk stratification, counselling and postnatal management planning.
Blood pressureRosa de Pinho, Luís Nogueira-Silva, José Lima Nogueira, Francisca Abecasis, Vasco Varela, Cláudia de Oliveira Pinho, Ana Catarina Gomes, Catarina Venda Grilo, …
BACKGROUND: Hypertension remains a leading contributor to cardiovascular mortality worldwide. However, integrated surveillance frameworks linking epidemiological burden, healthcare performance, and clinical outcomes remain limited. This study aimed to characterise hypertension epidemiology and management in Portuguese primary health care using real-world evidence from publicly-available indicators. METHODS: A retrospective ecological (aggregated group-level) study was conducted, using the five Portuguese mainland administrative health regions and the country as the units of analysis, with data obtained from Portuguese primary health care information systems from 2021-2025. Temporal and regional trends in hypertension prevalence and incidence, blood pressure (BP) monitoring and control, cardiovascular risk assessment, therapeutic review, prescribing patterns, and composite management indicators were assessed. A multidisciplinary expert panel provided structured clinical appraisal of indicator relevance and interpretability. RESULTS: Hypertension prevalence and incidence increased nationally, with regional heterogeneity. The Norte region showed higher performance across monitoring and control indicators, whereas Algarve and Alentejo exhibited generally poorer results. BP monitoring and control improved across all regions, with the proportion of hypertensive adults aged 18-64 years, with BP <140/90 mmHg increasing from 29.3% in 2021 to 65.0% in 2025. Composite management indicators improved, but the degree of improvement varied between different index versions. Medication costs generally increased up to 2024 but decreased afterwards, while prescription indicators remained stable. CONCLUSION: Hypertension management indicators in Portuguese primary care improved substantially between 2021 and 2025; however, regional disparities and methodological limitations remain. Current monitoring frameworks provide valuable real-world insights but incompletely capture clinically meaningful outcomes, supporting the need for more outcome-directed systems.
International journal of molecular medicineXiao Liang, Ming He, Tao Chen, Yan Liu, Yu-Ling Tian, Yu-Liang Wu, Yan Zhao, Yan Shen, Zu-Yi Yuan
Following the publication of the above paper, it has been drawn to the Editor's attention by a concerned reader that, for the immunohistochemical images shown in Fig. 3 on p. 1070, the 'SOCS3/HD/16W' and 'SOCS3/CD/28W' images were apparently the same, albeit with differently coloured shading, suggesting that this figure had been assembled incorrectly. In addition, upon analyzing the data in this paper independently in the Editorial Office, it came to light that one of the histological images featured in Fig. 2A (the 'Oil Red O/12W' image) apparently reappeared in a paper written by different authors at different research institutes in the journal Redox Biology several years after the publication of this article, albeit the image in that paper did not feature the same level of clarity. The authors have been contacted by the Editorial Office to offer an explanation for the apparently incorrect assembly of the data in Fig. 3, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office conitnues to investigate this matter further. [International Journal of Molecular Medicine 31: 1066‑1074, 2013; DOI: 10.3892/ijmm.2013.1323].
Clinical and experimental hypertension (New York, N.Y. : 1993)Zhongbo Chen, Wang Chunbin, Hanmei Zhang, Ting Luo, Jinhua Yan
Hypertension remains one of the leading modifiable risk factors for cardiovascular disease and premature mortality worldwide. Blood pressure (BP) management is particularly challenging in patients with coexisting type 2 diabetes (T2D), chronic kidney disease (CKD), or heart failure (HF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors have become an integral component of contemporary cardiorenal therapy and have consistently demonstrated additional BP-lowering effects across diverse clinical settings. This narrative review synthesizes the current clinical evidence regarding the antihypertensive effects of dapagliflozin and summarizes the biological mechanisms that may contribute to these effects, including osmotic diuresis and natriuresis, weight reduction, modulation of the sympathetic nervous system, enhanced uric acid excretion, and attenuation of oxidative stress, inflammation, and vascular dysfunction. Across clinical studies, reductions in systolic BP (SBP) generally exceed those in diastolic BP (DBP), although the physiological basis underlying this differential response remains incompletely understood. Dapagliflozin has demonstrated good tolerability and antihypertensive effects in clinical applications, its long-term use may be limited by the risk of genital infections. Collectively, the available evidence supports dapagliflozin as a cardiorenal therapeutic agent that may provide additional BP-lowering benefits in patients with hypertension and concomitant T2D, CKD, or HF, rather than as a substitute for conventional antihypertensive therapy. Future hypertension-focused clinical studies are warranted to further define its role in hypertension management.
Artificial cells, nanomedicine, and biotechnologyHuiqian Yang, Hongjie Du, Chunyan Zang, Jian Liu, Zheng Wang, Fenglei Xu, Hui Li, Xiaoming Li
This study aimed to identify key biomarkers for obstructive sleep apnoea (OSA) by analysing RNA-seq (GSE75097: 6 control and 42 OSA) and single-cell RNA-seq (GSE214865: 11 control and 11 OSA) datasets. Differential expression analysis revealed 575 DEGs between OSA and control groups. Using weighted gene co-expression network analysis (WGCNA) combined with machine learning approaches (Random Forest, SVM-RFE and LASSO), we identified four hub genes (C17ORF91, HBEGF, PGBD2 and ZNF616) as candidate biomarkers, showing exploratory discriminatory performance (AUC > 0.7). Gene set enrichment analysis (GSEA) revealed that these genes are associated with pathways related to hypoxia response, atherosclerosis and metabolic reprogramming (NES as low as -2.049, adj. p < .05), as well as immune regulation (NES up to 1.932, adj. p < .05). Single-cell RNA sequencing analysis further demonstrated that cMonocytes play a central role in OSA progression, exhibiting the highest scores for hypoxia, metabolic dysfunction and atherosclerosis risk. An exploratory nomogram incorporating these hub genes showed favourable internal performance within the discovery cohort. These findings provide hypothesis-generating insights into the molecular features associated with OSA and identify these genes as candidate biomarkers that require independent external and functional validation. Further validation of these genes may provide a basis for evaluating their potential diagnostic and therapeutic relevance in OSA.
Neurology. Clinical practiceShervin Badihian, Margarita Fedorova, Bradley Ashley Ong, Nicolas R Thompson, Neil Nero, Ken Uchino, Shumei Man
PURPOSE OF REVIEW: Digital health interventions are increasingly used in medicine to manage chronic conditions. However, the effectiveness, feasibility, and consistency of these interventions in poststroke risk factor management and secondary prevention remain uncertain. We conducted a systematic review and meta-analysis to evaluate the effect of digital health-supported interventions on vascular risk factor control among stroke survivors. We systematically searched MEDLINE, Embase, and Cochrane CENTRAL from inception through September 2025 for randomized, single-arm, and observational studies evaluating digital health interventions, defined as mobile health applications, wearable devices, or combined platforms, among adults with ischemic stroke, hemorrhagic stroke, or transient ischemic attack. Outcomes of interest included systolic and diastolic blood pressure, lipid levels, weight, physical activity, medication adherence, quality of life, and clinical events. Random-effects meta-analyses were performed for outcomes reported by ≥ 3 studies. Feasibility outcomes, including recruitment, retention, adherence, and usability were synthesized qualitatively. RECENT FINDINGS: Twenty-nine studies encompassing 8,389 participants were included. Digital health interventions were associated with modest reductions in systolic blood pressure compared with control conditions, including usual care and minimal-intervention comparators (pooled between-group mean difference, -5.8 mm Hg; 95% CI -9.9 to -1.6). However, prediction intervals crossed the null value, and between-study heterogeneity was substantial. No consistent effects were observed for diastolic blood pressure, lipid levels, or weight. Reporting of physical activity, medication adherence, and quality-of-life outcomes was heterogeneous, precluding quantitative pooling, although most studies reported favorable trends. Overall feasibility was high, with an aggregate dropout rate of 3.6% (95% CI 3.2%-4.0%) and high user acceptability across studies. Most trials enrolled participants with mild functional impairment and short follow-up durations (median ≈3 months). Few studies were powered to assess recurrent stroke or mortality. SUMMARY: Digital health-supported interventions for secondary stroke prevention seem feasible and acceptable, with evidence of modest short-term improvements in blood pressure. However, clinical effectiveness across other vascular risk factors remains inconsistent. In addition, substantial heterogeneity, short follow-up, and limited high-quality evidence constrain causal inference and preclude conclusions regarding sustained clinical benefit.
Physiotherapy research international : the journal for researchers and clinicians in physical therapyKinga Balla, Karl K Haase, Alexander Wick
BACKGROUND AND PURPOSE: Early mobilisation after myocardial infarction (MI) is strongly recommended. However, evidence regarding the benefits of structured physiotherapy during the acute in-hospital phase remains limited. This controlled clinical trial (CCT) aimed to evaluate whether an intensive early physiotherapy programme could improve health-related quality of life (HRQoL) and psychological well-being. METHODS: This CCT included 172 adults hospitalised after MI and treated with primary percutaneous coronary intervention (PCI). The participants were quasi-randomly allocated (1:1) to the intervention or control group based on the hospital room number. They received either an intensive physiotherapy programme (daily supervised mobilisation, education and graded activity) or standard medical care and an informational flyer. Primary outcomes included HRQoL (MacNew) and psychological well-being (Hospital Anxiety and Depression Scale, HADS-D). Clinically important changes were evaluated using the standardised response mean (SRM, which reflects the clinical relevance of observed changes), and the minimal clinically important difference (MCID, the smallest change in an outcome perceived as important by patients). Statistical analysis was conducted to assess group-by-time and pre-post interaction effects. RESULTS: Clinical significance metrics: The intervention group showed less deterioration in overall HRQoL (SRM: 0.04 vs. 0.1) and an enhancement in the MacNew emotional subscale (SRM: 0.22 vs. 0.09) compared with the control group. The HADS-D improved to a greater extent in the intervention group, exceeding the MCID (1.7 points). There were no statistically significant interaction effects between groups by time (interaction factor group * factor time; HRQoL p = 0.68 and anxiety/depression p = 0.15) or between the time points (pre-post, main effect factor time; HRQoL p = 0.35 and anxiety/depression p = 0.4). DISCUSSION: Clinically, intensive early in-hospital physiotherapy may lead to improved psychological outcomes and an attenuation of HRQoL decline. Although the change in HADS-D in the intervention group did not reach statistical significance, it exceeded the MCID, indicating a clinically meaningful improvement from the patients' perspective. The implementation of structured early mobilisation protocols may provide clinically relevant benefits during the acute post-PCI hospitalisation period and warrants further investigation. TRAIL REGISTRATION: Ethical approval was first submitted in January 2023, then resubmitted after minor revision in March 2023, and was then accepted on 15 March 2023 (Reg.Nr. K-2023-001).
BACKGROUND AND OBJECTIVES: Dizziness is a common emergency department (ED) concern, yet posterior-circulation strokes can be difficult to detect with standard clinical tools and neuroimaging alone. Quantitative video head impulse test (vHIT) provides an objective bedside measure of vestibulo-ocular reflex function and can help differentiate central from peripheral causes of acute dizziness. METHODS: We conducted a prospective, single-center feasibility and diagnostic-accuracy study of adults (18-90 years) presenting on an ED stroke pathway for acute dizziness. vHIT was performed within 48 hours of presentation, after completion of standard stroke evaluation. Two vestibular-trained clinicians, blinded to clinical and imaging data, classified vHIT as peripheral, central, equivocal, or poor quality. The reference standard (stroke vs nonstroke) was the final diagnosis adjudicated by stroke neurologists using all clinical information, noncontrast CT, and MRI when available. Diagnostic metrics for stroke were calculated for interpretable vHIT studies and in an intention-to-diagnose analysis. RESULTS: Thirty patients underwent vHIT; 11 (36.7%) had acute ischemic stroke and 19 (63.3%) had nonstroke diagnoses. Interpretable vHIT results (central or peripheral pattern) were obtained in 23 of 30 patients (76.7%). Overall, vHIT patterns were central in 19 (63.3%), peripheral in 4 (13.3%), equivocal in 3 (10.0%), and poor quality in 4 (13.3%). Among strokes, 9 of 11 (81.8%) had a central pattern and none had a peripheral pattern. In the primary analysis of interpretable studies, vHIT sensitivity and negative predictive value for stroke were both 100%, while specificity was 28.6% and overall accuracy was 56.5%. In the intention-to-diagnose analysis including all patients, sensitivity and negative predictive value remained 100%, with specificity at 21.1% and accuracy at 50.0%. DISCUSSION: Our findings suggest that vHIT was feasible in most ED stroke-pathway patients with acute dizziness and demonstrated high sensitivity and negative predictive value when a clearly peripheral pattern was present, supporting its potential role as an adjunctive rule-out tool. However, specificity was low, and nearly one-quarter of studies were equivocal or poor quality, limiting its use as a standalone diagnostic test. With further validation and larger studies, vHIT may help support more targeted use of hospital admissions, diagnostic workups, and ED stroke resources in patients without evidence of central pathology.
Annals of medicineSeonghyeon Bu, Jaehyuk Jang, Sang Hyun Kim, Jaeho Byeon, Kwan Yong Lee, Gyu-Chul Oh, Sungmin Lim, Eun Ho Choo, Ik Jun Choi, Byung-Hee Hwang, Chan Joon Kim, Mah…
BACKGROUND: The clinical effects of dual antiplatelet therapy de-escalation after acute myocardial infarction may differ by age. We evaluated whether the efficacy and safety of de-escalation from ticagrelor to clopidogrel differed by age in stabilized patients after percutaneous coronary intervention (PCI). PATIENTS AND METHODS: This was a prespecified secondary analysis of the TALOS-AMI randomized trial. Patients event-free 1 month after PCI receiving aspirin-ticagrelor were randomly allocated to de-escalation (aspirin-clopidogrel) or continuation (aspirin-ticagrelor). The primary net clinical endpoint was a composite of major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke) and Bleeding Academic Research Consortium types 2, 3, or 5 bleeding at 1 year. RESULTS: We included 2697 participants (mean age 60.0 ± 11.4 years; 16.8% women). Among patients aged <75 years (n = 2376), de-escalation reduced the primary net clinical endpoint (4.1% vs. 7.2%; adjusted hazard ratio (aHR), 0.54 [95% CI, 0.38-0.77]) and bleeding (2.8% vs. 4.9%; aHR, 0.54 [0.35-0.82]). Among patients aged ≥75 years, no significant differences were observed for the primary endpoint (6.4% vs. 11.6%; aHR0.54 [0.25-1.17]) or bleeding (3.2% vs. 7.9%; aHR, 0.41 [0.15-1.15]). Interaction testing showed no treatment effect modification by age for the primary endpoint (p for interaction = 0.978), MACE (p = 0.585), or BARC bleeding (p = 0.597). Among patients aged ≥75 years, 14/18 bleeding events occurred within 180 days. CONCLUSIONS: Among stabilized, event-free patients 1 month after PCI, no significant age-treatment interaction was observed; therefore, the efficacy and safety of de-escalation in older adults (≥75 years) remain uncertain. UNLABELLED: Trial registration: ClinicalTrials.gov (NCT02018055).
Neurology. Clinical practiceDavid O Acero-Garces, Eliza Gordon-Lipkin, Doris D M Lin, Lisa R Sun, Ryan J Felling, Philippe Gailloud, Matthew J Elrick, Carlos A Pardo, Haiwen Chen
BACKGROUND AND OBJECTIVES: Spinal cord stroke (SCS) is an underrecognized cause of severe acute myelopathy in children that can be misdiagnosed as an infectious or inflammatory process. Limited characterization of clinical and neuroimaging features of pediatric SCS impede timely and accurate diagnoses. Our objectives were to (1) identify clinical and radiologic features of SCS to prompt timely evaluation and accurate diagnosis and (2) gain insight into mechanisms of SCS. METHODS: We conducted a retrospective case analysis of children (<18 years old) diagnosed with SCS at a specialized referral institution between 2010 and 2025. Clinical records, imaging, and laboratory data were reviewed to identify key features of pediatric SCS. RESULTS: Among the 56 included patients, 28 were male (50%), and the age distribution was bimodal, with peaks at 1 and 14 years. Pediatric SCS presented with hyperacute onset of motor, sensory, bladder/bowel, and pain symptoms. The lesions were predominantly anterocentral, longitudinally extensive, with the cervical spinal cord being most often affected. Over time from the onset of symptoms, MRI diffusion restriction decreased, while gadolinium enhancement increased. CSF profile was noninflammatory in 95% of cases. Suspected mechanisms were identified in 63% of cases, with vascular compression being the most commonly identified mechanism in 17 participants (30%), while 38% were idiopathic. Chiari I malformations were identified as the main suspected cause of vascular compression, occurring in a subgroup of young patients with cervical SCS (n = 8, 14%). Serum studies identified hypercoagulability in 38% of the 40 participants evaluated. DISCUSSION: Recognition of specific clinical and neuroimaging profiles in pediatric patients with SCS may facilitate earlier identification and intervention. We propose a systematic evaluation of clinical history, with particular attention to the temporal course from symptom onset to nadir, early acquisition of spine MRIs with diffusion-weighted imaging sequences, serologic evaluations for hypercoagulability, and CSF studies to exclude inflammatory etiologies. This approach will provide a framework for continued efforts to better understand the mechanisms underlying pediatric SCS and develop prevention and treatment strategies.
Clinical and experimental hypertension (New York, N.Y. : 1993)Weijie Tang, Jinzhou Cai, Shibiao Zhang, Yichen Li, Mi Tang, Zilong Zheng, Zhi Tu, Xiuneng Li, Chengzhi Xu, Wangping Chen, Chengming Fan, Jinfu Yang
BACKGROUND: Pulmonary arterial hypertension (PAH) is a serious complication of congenital heart disease (CHD) with a left-to-right shunt, particularly ventricular septal defect (VSD). In patients presenting with severe PAH, therapeutic decision-making remains challenging because precise and individualized assessment criteria are lacking. In current clinical practice, treatment strategies are often based mainly on isolated hemodynamic parameters obtained by right heart catheterization (RHC), which may not fully reflect disease severity or reversibility. OBJECTIVES: This study aimed to explore an individualized treatment strategy for patients with severe VSD-PAH by analyzing the relationships among peripheral arterial oxygen saturation (SaO2), pulmonary vascular resistance (PVR), pulmonary-to-systemic blood flow ratio (Qp/Qs), and pulmonary-to-systemic pressure ratio (Pp/Pa). METHODS: We retrospectively analyzed 121 patients with isolated VSD and severe PAH admitted to our center between 2010 and 2020. All patients underwent RHC. Correlations between SaO2 and PVR, Qp/Qs, and Pp/Pa were assessed using Spearman correlation analysis. Patients were stratified according to SaO2 levels, and treatment strategies were compared across different hemodynamic profiles using Fisher's exact test. Based on these findings, we established a scoring system integrating SaO2, PVR, Qp/Qs, and Pp/Pa, and categorized total scores to examine their association with actual treatment strategies. RESULTS: The distribution of treatment strategies differed significantly across combinations of SaO2 and PVR, whereas Qp/Qs and Pp/Pa provided limited additional discrimination when SaO2 exceeded 93%. The proposed scoring system was associated with observed treatment patterns: patients with total scores ≥ 60 were predominantly managed surgically (with or without preoperative medical therapy), whereas those with scores <40 were mainly treated with medical therapy alone (93.7%). Intermediate score ranges were associated with mixed treatment patterns. CONCLUSIONS: Combining SaO2 with RHC-derived parameters provides a more comprehensive and individualized assessment of disease severity in VSD-PAH than hemodynamics alone. The proposed multidimensional scoring system may provide a hypothesis-generating framework for cardiovascular specialists.
Annals of medicineHe Huang, Gaonian Zhao, Su Jiang, Jiangwei Ma
Background: Patients with chronic coronary syndrome (CCS) are frequently complicated by reduced exercise tolerance. Previous studies exploring the relationship between body mass index (BMI) and cardiopulmonary function among CCS patients have reported conflicting results, and the definite association between the two indicators remains unclear. Accordingly, we performed this study to characterize their actual correlation.Methods: This retrospective study examined the association between BMI and Cardiopulmonary Exercise Testing (CPET) indices and the modifying effect of sex in 405 CCS patients recruited from the Cardiovascular Disease Center of Taizhou People's Hospital. Patients were divided into three groups based on BMI tertiles, and CPET parameters were compared. Multiple linear regression and sex-stratified analyses were conducted.Results: In patients with CCS, BMI exerted a bidirectional linear differential effect on cardiopulmonary exercise capacity without nonlinear inflection points: higher BMI correlated with greater PeakVO2 (B = 22.851, 95%CI: 16.180-29.522, β = 0.270, p < 0.001), yet lower Peak VO2/kg (B=-0.214, 95%CI: -0.310--0.117, β=-0.212, p < 0.001). This association was modified by sex. The positive association between BMI and PeakVO2 was stronger in males (B = 31.708, 95%CI: 21.609-41.806, β = 0.377, p < 0.001), whereas the negative inhibitory effect of BMI on Peak VO2/kg was more pronounced in females (B=-0.242, 95%CI: -0.370--0.115, β=-0.271, p < 0.001). Moreover, other determinants of cardiopulmonary function exhibited sex disparities.Conclusion: In patients with CCS, higher BMI was positively correlated with absolute peak exercise capacity but negatively correlated with peak VO2/kg, and this correlation showed sex heterogeneity.
The Libyan journal of medicineMadjda Akacha, Abdelhalim Khenchouche, Mounira Amrane, Abbas Mehnane, Abdelmadjid Lacheheb, Nasir A Ibrahim, Nosiba S Basher, Mohammed Saad Aleissa, Assia Derg…
The COVID-19 pandemic revealed the importance of pre-existing conditions, or comorbidities, as major predictors of disease severity and mortality worldwide. In this context, the major goal of this study was to examine the impact of common comorbidities on the clinical outcomes of COVID-19 patients in Sétif, Algeria, as well as to evaluate the local epidemiological risk profile. We conducted a thorough analysis of 12,932 COVID-19 participants in the Sétif community, focusing on the prevalence and impact of many illnesses, most notably diabetes, cardiovascular disease (CVD), and hypertension. We also looked at geographical inequalities in comorbidity prevalence to help influence local patient care methods. Our data revealed a strong link between these comorbidities and poor COVID-19 outcomes. Patients with heart disease, hypertension, and diabetes had a considerably greater incidence of severe COVID-19, with computed odds ratios (ORs) of 1.50, 1.34, and 2.89, respectively, indicating that diabetes was the best predictor of severity in this cohort. This investigation demonstrated that the presence of comorbidities considerably exacerbated the severity and mortality rate of SARS-CoV-2 infection. These findings highlight the importance of establishing thorough, personalised techniques and more effective diagnostic and treatment approaches for COVID-19 patients that explicitly account for the varied prevalence of underlying health issues.
Scandinavian cardiovascular journal : SCJMatilde Winther-Jensen, Berit Thornvig Philbert, Marie L Laursen, Jesper Kjaergaard, Tommi B Lindhardt, Jacob E Møller, Emilie Gregers, Louise Linde, Jens Broc…
INTRODUCTION: In patients who survive out-of-hospital cardiac arrest (OHCA), guidelines for implantation of an implantable cardioverter-defibrillator (ICD) are not unequivocal. METHODS: Patients resuscitated from OHCA of cardiac cause, without a reversible cause and an expected survival >1 year, were identified (year 2007-2011). Patients with acute coronary syndrome (ACS) and primary arrhythmia were compared with respect to: (1) incidence of early ICD-implantation prior to hospital discharge, (2) first shock- and anti-tachycardia (ATP) therapy up to 5 years, and (3) 5-year mortality rate assessed by Cox-regression analyses. RESULTS: ACS patients (n = 256) less often had an ICD implanted compared to primary arrhythmia patients (n = 258) (30% vs. 82%). Cumulative 5-year incidence of appropriate ICD-therapy did not differ (ATP; ACS: 28% vs. primary arrhythmia: 27%, shock; ACS: 22% vs. primary arrhythmia: 29%). Crude 5-year mortality was lower in ICD patients; ACS: No ICD: 22% vs. ICD: 13%; primary arrhythmia: No ICD; 66% vs. ICD: 16%. No difference in mortality between patients was noted (adjusted hazard ratio (HRACS): 0.91, 95% CI: 0.50-1.67). ICD implantation was independently associated with lower 5-year mortality risk in both patient groups after adjusting for cause of arrest, age > 65 years, left ventricular ejection fraction (LVEF) ≤35%, sex, and successful revascularization (in ACS only) (HRACS: 0.35, CI: 0.17-0.73, HRPA: 0.15, CI: 0.08-0.27). CONCLUSIONS: Cumulative incidences of appropriate therapy did not differ according to cause of arrest. Implantation of an early ICD after OHCA was significantly and independently associated with a lower 5-year mortality risk in both ACS and primary arrhythmia patients.
Scandinavian cardiovascular journal : SCJDeyu Qin, Guangxin Liu, Xinmeng Liu, Jingxiang Zhao, Qian Zhang, Mei Ma
BACKGROUND: Patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) show variable responses to exercise-based cardiac rehabilitation. We compared metabolic and exercise responder rates after adaptive postural balance cardiac rehabilitation exercise (APBCRE) versus aerobic exercise (AE) and explored baseline factors associated with responder status. METHODS: This pre-specified secondary analysis included 167 patients with CAD and T2DM from a randomized trial who completed an 8-week intervention (APBCRE, n = 87; AE, n = 80). Metabolic response was defined as an HbA1c reduction of ≥0.5%, and exercise response as a VO2max increase of ≥3.5 mL·kg-1·min-1. Multivariable logistic regression evaluated associated factors. RESULTS: APBCRE was associated with higher metabolic (48.3% vs 32.5%, p < 0.05) and exercise responder rates (31.0% vs 11.3%, p < 0.01) than AE. APBCRE was independently associated with metabolic response (OR 2.09, 95% CI 1.03-4.25; p = 0.043) and exercise response (OR 3.66, 95% CI 1.55-8.65; p = 0.003). Higher baseline HbA1c was associated with metabolic response (OR 5.04, 95% CI 2.14-11.86; p < 0.001), whereas insulin therapy was inversely associated (OR 0.25, 95% CI 0.07-0.90; p = 0.034). Lower baseline VO2max was associated with exercise response (OR 0.84, 95% CI 0.72-0.97; p = 0.016). CONCLUSIONS: APBCRE was associated with higher rates of clinically meaningful metabolic and exercise responses than AE. Responder analysis complements conventional outcome assessment and may support individualized cardiac rehabilitation.
Clinical and experimental hypertension (New York, N.Y. : 1993)Ronald McMillan, Mohammad Saleem, Ariel Thorson, Olivia Pierre-Louis, Selam Desta, Lale A Ertuglu, Celestine N Wanjalla, Lindsey Stolze, Quanhu Sheng, Naome Mw…
Salt-sensitivity of blood pressure (SSBP) is a significant cardiovascular risk factor, but its underlying immunometabolic mechanisms remain unclear. Chemerin, an adipose-derived inflammatory mediator linked to vascular dysfunction, was studied in 30 hypertensive adults (mean age 53.1 years; 53% female; mean BMI 32.1 kg/m2) during an inpatient salt-sensitivity protocol. Participants underwent salt-loading and salt-depletion phases over three days. Plasma and urine chemerin levels were measured, alongside immune cell phenotyping and transcriptomic profiling using CITE-seq, RNA-seq, and NanoString. Plasma chemerin increased significantly from salt-loading to salt-depletion (100.4 to 125.8 pg/mL; p = 0.008) and was higher in salt-sensitive individuals during depletion (141.2 vs. 108.6 pg/mL; p = 0.02). Plasma chemerin correlated with systolic blood pressure (SBP) during salt depletion (R2 = 0.20, p = 0.01), while urinary chemerin increased but did not correlate with SBP. In vitro, high-sodium media suppressed CMKLR1 (chemerin receptor) expression in monocytes (p < 0.01). CITE-seq revealed a 1.8-fold enrichment of CMKLR1 in classical monocytes in salt-resistant individuals compared to salt-sensitive ones, with CMKLR1 inversely correlating with ΔSBP (R2 = 0.47, p = 0.03) and ΔMAP (R2 = 0.72, p = 0.004). CMKLR1 was linked to glycolytic and oxidative phosphorylation gene upregulation, and its expression in dendritic cells correlated with urinary lactate and fumarate levels. The chemerin-CMKLR1 axis is dysregulated in SSBP, influencing monocyte and dendritic cell metabolism and blood pressure. Chemerin and CMKLR1 may serve as biomarkers and therapeutic targets for salt-sensitive hypertension.
BACKGROUND: Reliable tracking of short- and long-term blood pressure (BP) changes is a prerequisite for clinical adoption of cuffless BP devices. This study evaluated the 6-week stability of BP estimation by CSEM's wearable photoplethysmography (PPG)-based cuffless BP monitor and its ability to track BP changes in hypertensive patients compared with a validated oscillometric device (Microlife WatchBP Home A). METHODS: In this feasibility method-comparison study, 30 hypertensive patients attended four visits over 6 weeks. At each visit, BP was estimated as the median of 5-7 consecutive measurements obtained with the cuff-based (Cuff BP) and cuffless (PPG BP) devices. Between-visit systolic and diastolic BP changes (ΔSBP, ΔDBP) were compared between devices. Concordance rate (CR), defined as the percentage of significant BP changes (ΔSBP >15 mmHg, ΔDBP >10 mmHg) showing the same direction with both devices, was also assessed. RESULTS: Thirty participants (18 women; age 54 ± 17 years; BMI 29.2 ± 5.5 kg/m²) were included. Differences between devices were 0.2 ± 12.8 mmHg for ΔSBP and -0.1 ± 7.4 mmHg for ΔDBP. No temporal drift in differences between Cuff ΔBP and PPG ΔBP was observed over 6 weeks. CR for significant BP changes was 83% for SBP and 86% for DBP. CONCLUSION: CSEM's wearable cuffless BP monitor provided stable BP estimation and concordant BP tracking during antihypertensive therapy. Interpretation is tempered by substantial variability of the oscillometric reference device. If confirmed in larger studies against a gold-standard reference, these findings could support the clinical acceptance of wearable cuffless BP monitoring.
Stress (Amsterdam, Netherlands)Viola Vaccarino, Amit J Shah, Puja K Mehta, Brad Pearce, Paolo Raggi, J Douglas Bremner, Arshed Quyyumi
Recognition of a "brain-heart axis" has grown substantially, highlighting the contribution of psychological stress on cardiovascular physiology and the development and progression of cardiovascular disease (CVD). This connection appears particularly consequential for individuals with established CVD. Laboratory-based mental stress paradigms have been central to uncovering the mechanisms linking psychological stress with cardiovascular outcomes, implicating autonomic dysregulation and its downstream effects on immune function, vascular reactivity, and myocardial ischemia. Dynamic alterations in autonomic and molecular pathways during stress or negative emotional states may serve not only as critical determinants of cardiovascular risk but also as potential markers of heightened vulnerability. Certain patient groups-women, individuals with mental health conditions, and those facing adverse psychosocial exposures such as racial minorities-are especially susceptible to these stress-related effects. Recent advances extend these insights beyond controlled laboratory settings, demonstrating that ambulatory assessments of autonomic physiology are related to momentary psychological states in everyday life. This updated review synthesizes emerging knowledge on mind-body interactions in CVD and outlines promising avenues for future intervention. Collectively, the evidence underscores the importance of an integrative framework that considers psychological and biological processes jointly to fully understand the pathophysiology and outcome of CVD.
PulmonologyXiu Shi, Jinyan Ke, Xiaofeng Wu, Yuhan Wang, Yixuan Wang
BACKGROUND: Whether supranormal lung function is associated with incident atrial fibrillation (AF), and whether obstructive sleep apnoea (OSA) modifies this association, remain to be determined. METHODS: We analysed 2,408 participants from the Sleep Heart Health Study who were free of AF at baseline and had no spirometric airflow obstruction. The primary analysis classified forced expiratory volume in 1 second (FEV1) as below normal, normal, or supranormal using race-neutral Global Lung Function Initiative (GLI) Global (2022) reference equations. Categories defined by forced vital capacity (FVC) were examined in a secondary analysis. Associations with incident AF were evaluated using multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Firth penalised logistic regression and sensitivity analyses were used to assess the robustness of the findings. Interaction with OSA was explored. RESULTS: Among 2,408 participants, 282 developed AF. Compared with normal FEV1, supranormal FEV1 was associated with lower odds of incident AF in the primary adjusted model (OR, 0.420; 95% CI, 0.198-0.888). The corresponding Firth estimate was 0.443 (95% CI, 0.199-0.869). Supranormal FVC showed a similar association in standard logistic regression (OR, 0.351; 95% CI, 0.167-0.736) and Firth penalised logistic regression (OR, 0.371; 95% CI, 0.168-0.721). The direction of the associations was generally consistent across sensitivity analyses. There was no statistically significant evidence of effect modification by OSA. CONCLUSIONS: Supranormal lung function was associated with lower odds of incident AF. These findings support supranormal spirometry as a potential marker of favourable systemic and cardiopulmonary physiology.
Biomaterials advancesLanbo Shen, Jiahao Yu, Tingting Kong, Xin Huang, Bin Li, William W Yu
Myocardial infarction (MI) causes irreversible cardiomyocyte loss and adverse ventricular remodeling, yet current cardiac patches remain limited by inadequate bioactivity and poor electrical integration with host myocardium. We report a multifunctional metal-phenolic conducting polymer hydrogel (CPH) for post-infarction myocardial repair. A one-pot process integrates a conductive polypyrrole network with dynamic Cu2+-tannic acid (TA) coordination, thereby combining electrical conductivity, mechanical support, and redox-related functionality within a single hydrogel. Cu-TA CPH exhibited myocardium-matched mechanical properties (∼19 kPa), suitable conductivity, good biocompatibility, and intrinsic antioxidant and antibacterial activities. These combined features enabled the hydrogel patch to provide mechanical support, facilitate electrical communication, and improve the local microenvironment after MI. On postoperative day 7, left ventricular ejection fraction in the Cu-TA CPH-treated MI group was higher than that in the MI group receiving no material treatment. This therapeutic effect was associated with an increased Bcl-2/Bax ratio, enhanced VEGFR-1 expression, reduced infarct size, and improved myocardial tissue preservation. Collectively, Cu-TA CPH represents a promising hydrogel patch for post-infarction myocardial repair.
OBJECTIVES: This study aimed to investigate Investigate the expression level, prognostic value, and biological function of miR-877-5p in MM. METHODS: A total of 103 MM patients and 98 non-tumor controls were included in the study. miR-877-5p expression level was verified by RT-qPCR, and its prognostic value was evaluated through Kaplan-Meier and the Cox regression model. MM cell proliferation and apoptosis were assessed with the CCK‑8 assay and flow cytometry. The potential target genes of miR-877-5p were predicted by bioinformatics analysis and verified by dual luciferase assay. Rescue assays confirmed that MAPK8 mediates the regulatory function of miR-877-5p. RESULTS: miR-877-5p was reduced in MM, and its low level was associated with a poorer overall survival of patients, being an independent prognosticator of poor survival in MM. Function experiments confirmed that overexpression of miR-877-5p could inhibit the proliferation of MM cells and promote apoptosis. Mechanistically, MAPK8 was a direct downstream target of miR-877-5p. MAPK8 was upregulated in MM and negatively correlated with miR-877-5p levels. Rescue assays were conducted to verify that MAPK8 overexpression reversed the effect of miR-877-5p on MM cell proliferation and apoptosis. DISCUSSION: These findings indicate that miR-877-5p exerts tumor-suppressive functions in MM, likely through negative regulation of MAPK8. The miR-877-5p/MAPK8 axis may represent a novel regulatory pathway involved in MM progression. CONCLUSIONS: miR-877-5p acts as a tumor suppressor in MM and may serve as a potential biomarker for prognosis assessment. Its regulatory role in MM progression is likely mediated through targeting and inhibiting MAPK8.
Renal failureSiyuan Gong, Yonghong Xiong, Wenyuan Li, Yan Leng, Xinqi Deng, Bihan Wang, Baichuan Yang, Yuhang Yang, Wei Li
Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury and is associated with mitochondrial dysfunction, excessive reactive oxygen species (ROS) production, and tubular cell apoptosis. Sigma-1 receptor (Sigma1R), an intracellular chaperone, helps maintain mitochondrial homeostasis and cell survival. Here, Sigma1R expression was significantly downregulated in renal IRI. Fluvoxamine treatment ameliorated renal dysfunction and reduced apoptosis in vivo, whereas Sigma1R overexpression preserved mitochondrial membrane potential and attenuated ROS accumulation in HK-2 cells subjected to hypoxia/reoxygenation. The findings support the functional involvement of Rac1 in Sigma1R-mediated enhancement of PINK1/Parkin-mediated mitophagy, which may facilitate the clearance of damaged mitochondria and restore mitochondrial quality control. Overall, Rac1 is involved in Sigma1R-mediated mitophagy and mitochondrial protection, highlighting Sigma1R as a potential therapeutic target for renal IRI.
Stroke remains one of the leading causes of death and long-term disability worldwide, with neuroinflammation and metabolic dysfunction playing central roles in its pathogenesis. In this study, we investigated the function of Y-box binding protein 3 (YBX3) in ischemic stroke, with particular focus on its regulation of glycolysis and neuroinflammatory responses. Using a middle cerebral artery occlusion (MCAO) model in C57BL/6 mice and an oxygen-glucose deprivation/reperfusion (OGD/R) model in BV2 microglia, we observed that YBX3 expression was markedly upregulated following ischemia-reperfusion. Overexpression of YBX3 aggravated cerebral infarct size, worsened motor and neurological outcomes, and increased the release of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) both in vivo and in vitro. Mechanistically, YBX3 enhanced glycolysis in BV2 cells by stabilizing pyruvate kinase M2 (PKM2) mRNA and promoting its expression, while simultaneously activating glycolysis through the mTOR-HIF-1α signaling pathway. Pharmacological inhibition of mTOR with rapamycin reversed YBX3-induced glycolytic activation, neuroinflammation, and neuronal injury. Collectively, these results identify YBX3 as a key regulator of ischemic brain damage through glycolysis-dependent mechanisms and underscore its potential as a therapeutic target for stroke.
Redox report : communications in free radical researchJianzhen Lei, Yueru Kong, Chao Ye, Chuanyue Zhang, Yi Shen, Xin Wu, Qiuyue Wu, Ying Han, Min Chen, Yueqi Song, Qing Yan, Fen Zheng, Xinyi Xia
OBJECTIVES: Pathological arterial remodeling heavily depends on the aberrant proliferation and migration of vascular smooth muscle cells (VSMCs). This study explores how γ-Glutamylcysteine (γ-GC) regulates VSMC signaling to mitigate hypertensive structural damage. METHODS: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats received intraperitoneal injections of γ-GC (100 mg/kg) every two days for 4 weeks. Blood pressure and arterial remodeling were evaluated. Primary aortic VSMCs were cultured for cellular mechanism analysis. To verify Nrf2 pathway requirement, the Nrf2 inhibitor ML385 was applied in vitro and via osmotic pumps in vivo. RESULTS: γ-GC lowered systemic blood pressure and prevented arterial medial thickening in SHR, while normotensive controls remained unaffected. In SHR-VSMCs, γ-GC inhibited cell migration, proliferation, and phenotypic switching, and alleviated cellular oxidative stress. RNA-seq revealed significant enrichment of the Nrf2 signaling pathway. Mechanistically, γ-GC induced Keap1 S-glutathionylation, which disrupted the Keap1 and Nrf2 interaction and promoted Nrf2 nuclear translocation. Notably, Nrf2 inhibition with ML385 abolished the protective effects of γ-GC in vivo and in vitro. DISCUSSION: γ-GC attenuates hypertensive arterial remodeling by modulating intracellular signaling, specifically through Keap1 S-glutathionylation-dependent Nrf2 activation. The Keap1/Nrf2 signaling axis is required for γ-GC to restore VSMC function, suggesting a targeted molecular mechanism for cardiovascular protection.