Development Of Disease Research Articles

Association between CD20+ T lymphocytes and neuropsychological findings in multiple sclerosis.

CD20+ T lymphocytes are a subset of circulating T cells presenting the CD20+ receptor, a molecular marker of B lineage. CD20+ T lymphocytes are thought to play a pivotal role in multiple sclerosis (MS) pathology, especially at progressive stages. We aimed to investigate the correlation between CD20+ T lymphocytes and neuropsychological features (i.e., cognition, depression, anxiety, fatigue, and sleep quality) in MS patients. We enrolled 90 MS patients. Each patient underwent cognitive assessment (Brief International Cognitive Assessment for Multiple Sclerosis) and psychometric assessment (modified Fatigue Impact Scale, Beck Anxiety Inventory, Beck Depression Inventory, Pittsburgh Sleep Quality Index). Cognitive status was defined through the cerebral functional score. Forty-four of 90 patients were relapsing-remitting (49%) and 46 were progressive patients (51%). Seventy patients (18.9%) showed CD20+ T lymphocytes in peripheral blood with a mean level of 0.38 ± 1.2%. Patients with CD20+ T lymphocytes were more likely to be at progressive phases (76.5% vs. 23.5%, p = 0.02) and showed a higher Expanded Disability Status Scale score (median [range] = 6.0 [1.5-7.5] vs. 3.5 [1-7.5], p = 0.001). Moreover, patients with CD20+ T lymphocytes showed worse cognitive functioning (p = 0.004), higher global fatigue symptoms (p = 0.02), higher cognitive fatigue (p = 0.01), higher psychosocial fatigue (p = 0.005), and a trend toward worse sleep quality (p = 0.06). The presence of CD20+ T lymphocytes in the peripheral blood of MS patients was associated with worse neuropsychological functioning and progressive disease stages. Peripheral CD20+ T lymphocytes could potentially serve as markers for both disease progression and development of fatigue in MS patients.

U-shaped association of serum vitamin A concentrations with all-cause mortality in patients with NAFLD: results from the NHANES database prospective cohort study

BackgroundPrevious studies have demonstrated a significant association between serum vitamin A concentration and non-alcoholic fatty liver disease (NAFLD) development. However, the long-term prognostic implications of serum vitamin A in patients with NAFLD remain underexplored. This study aims to investigate whether there exists a correlation between serum vitamin A concentrations and overall mortality among subjects diagnosed with NAFLD.MethodsTo investigate the association between serum vitamin A concentrations and NAFLD outcomes, we conducted prospective cohort studies using data from the 1999–2006 and 2017–2018 National Health and Nutrition Examination Survey (NHANES). We utilized a multivariate Cox regression model to explore the relationship between serum vitamin A levels and all-cause mortality. Survival curves related to serum vitamin A were constructed using the Kaplan–Meier method. Additionally, the restricted cubic splines (RCS) method was applied to examine potential nonlinear relationships between serum vitamin A concentrations and all-cause mortality of NAFLD.ResultsOver a median follow-up period of 10.3 years, a total of 1,399 all-cause deaths were recorded. The weighted average concentration of serum vitamin A was 61.48 ± 0.37 μg/dL. After adjusting for potential confounders, a significant U-shaped relationship was identified between serum vitamin A concentrations and the risk of all-cause mortality in NAFLD patients. This relationship was particularly pronounced in men and elderly individuals aged 60 to 85.ConclusionOur study reveals a significant non-linear relationship between serum vitamin A concentrations and the risk of all-cause mortality in patients with NAFLD. These findings underscore the importance of monitoring and maintaining optimal serum vitamin A levels to potentially improve survival outcomes in NAFLD patients.

Pharmacological Manipulation of the Aging Pathways to Effect Health Span and Lifespan with Special Reference to SGLT2 Inhibitors as Powerful Anti-aging Agents in Humans

Calorie restriction has been shown to slow the aging process in numerous organisms including primates. Caloric excess states, such as type 2 diabetes, are associated with accelerated aging and the incidence and severity of chronic diseases. The nutrient-sensing pathways and intestinal microbiome are important systems that affect aging and chronic disease development. This manuscript reviews the various pathways involved with aging and chronic disease development and examines the pharmacological manipulation of these systems which appear to slow aging and the chronic diseases of aging in experimental model organisms and collaborating human data when available. Finally, the abundance of experimental and human data suggesting the newer diabetic medications, the sodium-glucose transport inhibitors, are potent anti-aging agents is provided.

Diet and Disease Development: Mechanisms, Prevention, and Treatment

The overall aims of this Special Issue “Diet and Disease Development: Mechanisms, Prevention and Treatment” are to describe and emphasise the importance of diet in disease development; understand the mechanism(s) whereby an unhealthy diet can induce various diseases; examine the potential effects of natural compounds or extracts on disease prevention or treatment; and determine whether nutrients and their metabolites can be used as biomarkers to diagnose certain diseases [...]

Diet and Disease Development: Present and Future

The present Editorial provides an overview of the Special Issue “Diet and Disease Development” recently published in Nutrients [...]

Clinical characteristics of patients with granulomatous lobular mastitis associated with Corynebacterium parakroppenstedtii infection and drug sensitivity analysis of the isolated strains

BackgroundIt is presently considered that Corynebacterium especially Corynebacterium kroppenstedtii (CK) infection, is one of the important causes of granulomatous lobular mastitis (GLM). However, the pathogen of mastitis in the past two years has been identified as a newly discovered Corynebacterium. But it is unclear whether the pathogen associated with the occurrence of GLM is also this bacterium.MethodsGLM female patients with positive bacterial culture in pus specimens from February 2023 to February 2024 who were identified as CK infection by mass spectrometer were selected as the research objects in this study, and the clinical isolates were identified by 16S rDNA sequencing technology to identify the specific pathogen of GLM-related bacterial infection. Subsequently, the clinical characteristics of the patients were compared with those of GLM patients without bacterial infection during the same period, to explore the effect of this particular type of Corynebacterium infection on disease development in GLM patients. Finally, we tested the minimum inhibitory concentration (MIC) values of antibiotics when inhibiting these separation strains in vitro through the E-Test experiment, to evaluate their medicine sensitivity.ResultsA total of 31 GLM patients initially diagnosed with Corynebacterium kroppenstedtii (CK) infection via MALDI-TOF MS were enrolled in the study. However, subsequent 16S rDNA sequencing revealed that 28 isolates (90.32%) were actually identified as the newly recognized Corynebacterium parakroppenstedtii (CPK). This discovery challenges the conventional belief that CK is the primary pathogen of GLM, suggesting instead that CPK is the predominant pathogen associated with GLM bacterial infections. Comparative analysis of the clinical characteristics between the two groups revealed a significantly higher recurrence rate among CPK-infected GLM patients compared to those without CPK infection, along with elevated prolactin levels (P < 0.05). The sensitivity test results indicated high sensitivity of the isolates to vancomycin, linezolid, and rifampicin.ConclusionIn conclusion, this study highlights that Corynebacterium kroppenstedtii strains isolated from GLM specimens were Corynebacterium parakroppenstedtii, serving as the primary pathogen closely linked to GLM’s occurrence. CPK infection significantly increases the risk of recurrence in GLM patients, with elevated prolactin levels potentially playing a pivotal role in this process. In clinical antimicrobial treatment, antimicrobials other than penicillin and ciprofloxacin may be empirically administered when sensitivity test results are inconclusive.

Morphological characterization of glial cells in the &lt;i&gt;Substantia nigra&lt;/i&gt; of spontaneously hypertensive SHR rats

BACKGROUND: Substantia nigra is the main dopaminergic center of the brain. Massive loss of dopaminergic neurons is characteristic for Parkinson’s disease. Arterial hypertension is considered a possible risk factor for Parkinson’s disease development, but to date there is no understanding of the mechanisms that may mediate the effect of high blood pressure on the death of dopaminergic neurons and the development of Parkinson’s disease. Since neuroglia is known to make a major contribution to the pathogenesis of neurodegeneration, it is important to evaluate the effect of arterial hypertension on the functional status of glial cells in the Substantia nigra. AIM: The aim of the study was to analyze the features of morphofunctional state of both microglia and astroglia in the Substantia nigra of spontaneously hypertensive rats. MATERIALS AND METHODS: Brain samples from Wistar rats (n = 3) and from spontaneously hypertensive SHR rats aged 9 months (n = 4) were used as a material for the study. Brain sections were immunostained for tyrosine hydroxylase to identify the Substantia Nigra, for calcium-binding protein Iba-1 to identify microglia, and for glial fibrillary acidic protein to identify astrocytes. RESULTS: Compared to the control, microglial cells in the Substantia nigra of spontaneously hypertensive rats show signs of moderate activation manifested in significant thickening of the processes of microgliocytes. Single microgliocytes exhibit ameboid morphology, indicating their strong activation. A close spatial relationship with the bodies of dopaminergic neurons was noted for some identified microgliocytes. Astrocytes in Substantia nigra of both Wistar rats and SHR rats show no signs of activation. CONCLUSIONS: Arterial hypertension may be one of the causes of neuroinflammation mediated by microglia in the Substantia nigra.

Unilateral biportal endoscopic vs. open surgery in the treatment of young obese patients’ lumbar degenerative diseases: a retrospective study

BackgroundObesity accelerates the development of lumbar disease and increase the risk during surgery. Unilateral biportal endoscopic discectomy (UBE) is a newly developed minimally invasive technique, which refers to the spinal surgery under unilateral double-channel endoscopic surgery. Therefore, the purpose of this study is whether UBE decompression alone can bring good clinical results to young obese patients with lumbar degenerative diseases.MethodsThe patients with lumbar diseases who underwent UBE and open surgery (open discectomy) in our hospital from February 2020 to February 2022 were selected as young (age ≤ 44 years old) and obesity (BMI ≥ 30 kg/m2). The patients were evaluated with VAS, ODI, JOA and modified Macnab score before operation, 1 month, 6 months and 12 months after operation. Nerve root function sensation, muscle strength and tendon reflex were evaluated. The operation time, estimated blood loss, postoperative hospital stay, incidence of postoperative complications and reoperation rate were recorded. MRI quantitative lumbar multifidus muscle (LMM) comparison was performed 12 months after operation.Results77 patients were included, and the scores of VAS, ODI and JOA were similar in the two groups during the last follow-up. There were no difference in nerve root function sensation, muscle strength or tendon reflex. However, one month after operation, the VAS back score and ODI improvement in the UBE group were significantly better than those in the open group, which were 2.44 ± 0.97, 33.10 ± 6.78 and 2.93 ± 0.79 and 36.13 ± 5.84, respectively, with a statistically significant difference (p = 0.020 and 0.038). According to the modified Macnab criteria, UBE group, the excellent and good rate was 97.2%. The excellent and good rate of open group was 97.6%. The estimated blood loss and postoperative hospital stay in UBE group (36.81 ± 17.81, 3.92 ± 1.32) were significantly better than those in open group (104.88 ± 31.41, 6.41 ± 1.94), with a statistically significant difference (p = 0.010). There was no significant difference in operation time between the two groups (p = 0.070). The number of complications in UBE group was 2 (5.6%) and open group was 4 (9.8%). The fat infiltration rate of 19.3%+11.0% in UBE group was significantly lower than that of 27.0%±13.9% in open group (p = 0.010).ConclusionUBE has the advantage of early recovery in the treatment of lumbar degenerative diseases in young obese patients, and reduces the damage to LMM, so it has a good clinical effect.

Environmental Pollution and Oxidative Stress: Health Effects During Pregnancy: A Review

Oxidative stress is an imbalance between reactive oxygen species production and antioxidant defense that can lead to reproductive disorders and poor pregnancy outcomes. Environmental pollution under climate change is involved in reactive oxygen species formation and may cause various dysfunctions of the reproductive system. Oxidative stress is a widespread factor that affects the physiology of the male and female reproductive systems, leading to high levels of DNA damage and infertility. Miscarriage, preeclampsia, and premature birth are all linked to oxidative stress. Environmental pollution induces excesses of oxidative stress by expanding ROS generation or overwhelming the physiological responses of the antioxidant defense system. This increases cellular damage, inflammation, and the development of numerous diseases. Here, we present a brief outline of the physiological and developmental roles that oxidative stress plays during pregnancy. We also offer some insights into the underlying mechanisms that have been put forth, which culminate in a summary of the harmful effects of oxidative stress that have an environmental origin in pregnancy-related complications. The current work may motivate the design of more focused wellbeing measures in order to prevent and promote human health and anticipate unfavorable pregnancy outcomes.

Alleviation of oxidized lipid-induced oxidative stress and hypertension by estrogen and selected antihyperlipidemic drugs in post-menopausal Wistar rats

Lipid peroxidation is implicated in the development of hypertension and coronary artery disease, and its deleterious impact is exacerbated by estrogen (ETD) depletion in post-menopausal women. We hypothesize that treatment with ETD and antihyperlipidemic drugs, either alone or in combination, can alleviate the development of cardiovascular disease. In this study, female Wistar rats were divided into 10 groups (n = 6): Group 1 (control) underwent a Sham operation and was fed standard rat chow, whereas the other nine groups were ovariectomized (OVX) and received a diet containing either thermoxidized palm oil (TPO) or thermoxidized soya oil (TSO) for 12 weeks. ETD at 0.2 mg/kg/day, atorvastatin (ATV) at 10 mg/kg/day, and a combination of ezetimibe (EZE) and ATV (EZE at 3 mg/kg/day + ATV at 10 mg/kg/day) were administered for 12 weeks in both TSO and TPO diet groups. Blood pressure and electrocardiogram (ECG) parameters were assessed, along with serum lipid profile, atherogenic indices, and markers of oxidative stress. Both TPO and TSO diets significantly altered blood pressure and ECG parameters in OVX rats. Treatment with ATV, EZE+ATV, and ETD significantly reduced blood pressure parameters compared to the OVX+TPO group. Antihyperlipidemic drugs significantly decreased heart rate, QT interval, QRS duration, and QT corrected (QTc), whereas ETD similarly shortened the QRS and QTc duration. ATV and ETD also reduced total cholesterol, triglycerides, and very low-density lipoprotein levels, while boosting high-density lipoprotein concentrations compared to untreated OVX+TSO rats. This study demonstrates that thermoxidized oil has a deleterious effect on OVX rats by altering blood pressure, ECG parameters, and atherogenic indices. Treatment with antihyperlipidemic drugs and ETD normalized blood pressure and ECG parameters, reversed hyperlipidemia, and restored antioxidant system balance.

Circulating Neoplastic-Immune Hybrid Cells Are Biomarkers of Occult Metastasis and Treatment Response in Pancreatic Cancer

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) presents significant diagnostic and prognostic challenges, as current biomarkers frequently fail to accurately stage disease, predict rapid metastatic recurrence (rPDAC), or assess response to neoadjuvant therapy (NAT). We investigated the potential for circulating neoplastic-immune hybrid cells (CHCs) as a non-invasive, multifunctional biomarker for PDAC. Methods: Peripheral blood specimens were obtained from patients diagnosed with PDAC. CHCs were detected by co-expression of pan-cytokeratin and CD45, normalized to 50,000 peripheral blood mononuclear cells. rPDAC was defined as metastatic recurrence within six months of margin-negative pancreatectomy. Cyclic immunofluorescence (CyCIF) analyses compared hybrid phenotypes in blood and tumors. Results: Blood samples were collected from 42 patients with PDAC prior to resection. Those with radiographically occult metastatic disease and rPDAC had higher preoperative CHC numbers compared to patients who did not (65.0 and 74.4, vs. 11.52 CHCs; p &lt; 0.001). Patients with complete or near-complete pathologic responses to NAT had lower preoperative CHC numbers than partial and/or non-responders (1.7 vs. 13.1 CHCs; p = 0.008). When assessed longitudinally, those with partial pathologic response saw CHC levels become undetectable while on treatment but increase in the interval between NAT completion and resection. In contrast, patients with poor responses or development of metastatic disease experienced persistent CHC detection during therapy or rising levels prior to radiographic evidence of metastases. Further, in metastatic PDAC patients, treatment-induced phenotypic changes in hybrid cells mirrored those in paired metastatic tumor samples. Conclusions: CHC enumeration and phenotyping display promise as a real-time indicator of disease burden, recurrence risk, and treatment response in PDAC. CHCs have great potential as tumor-derived biomarkers to optimize therapeutic strategies and improve survival in patients with PDAC.

The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository in the AIRR Data Commons: a practical guide for access, use and contributions through the Type 1 Diabetes AIRR Consortium.

Human molecular genetics has brought incredible insights into the variants that confer risk for the development of tissue-specific autoimmune diseases, including type 1 diabetes. The hallmark cell-mediated immune destruction that is characteristic of type 1 diabetes is closely linked with risk conferred by the HLA class II gene locus, in combination with a broad array of additional candidate genes influencing islet-resident beta cells within the pancreas, as well as function, phenotype and trafficking of immune cells to tissues. In addition to the well-studied germline SNP variants, there are critical contributions conferred by T cell receptor (TCR) and B cell receptor (BCR) genes that undergo somatic recombination to yield the Adaptive Immune Receptor Repertoire (AIRR) responsible for autoimmunity in type 1 diabetes. We therefore created the T1D TCR/BCR Repository (The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository) to study these highly variable and dynamic gene rearrangements. In addition to processed TCR and BCR sequences, the T1D TCR/BCR Repository includes detailed metadata (e.g. participant demographics, disease-associated parameters and tissue type). We introduce the Type 1 Diabetes AIRR Consortium goals and outline methods to use and deposit data to this comprehensive repository. Our ultimate goal is to facilitate research community access to rich, carefully annotated immune AIRR datasets to enable new scientific inquiry and insight into the natural history and pathogenesis of type 1 diabetes.

Expression profiles of genes involved in lignan synthesis in developing flax seeds

Flax seeds are the richest plant source of lignans, which prevent the development of many diseases. Secoisolariciresinol diglucoside (SDG) is the predominant lignan in seeds of the cultivated species Linum usitatissimum. We sequenced transcriptomes of flax seeds at five developmental stages for 8 varieties differing in lignan content grown under three different conditions and evaluated the expression of PLR1 and UGT74S1 genes, which play a key role in SDG synthesis. The co-expression of PLR1 and UGT74S1 genes was detected, and the expression level of these genes was observed to change tens and hundreds of times during seed development, confirming their role in SDG synthesis in flax seeds. Low temperature (16 °С) and abundant watering resulted in a shift of the maximum expression level of both genes to later dates (14th day after flowering) compared to poor watering and high temperature (24 °С) and optimal conditions (20 °С) (7th day after flowering). Meanwhile, the expression level of PLR1 and UGT74S1 genes was lower under high temperature and poor watering than under optimal conditions. No association was found between lignan content in seeds of the studied flax varieties and the expression level of PLR1 and UGT74S1 genes. Our results provide important information on the contribution of genotype and environment to the expression of key genes of SDG synthesis, which is also necessary for the development of optimal approaches to obtain lignan-rich flax seeds.

Elevated Circulatory Levels of UL16 Binding Protein 1 Positive Microparticles Are Associated With Acute Myocardial Infarction and its Severity.

Atherosclerosis is a vascular inflammatory disease characterized by the activation and stress of various inflammatory cells, leading to the development of coronary artery disease and subsequently acute myocardial infarction (AMI). Among AMI cases, ST-segment elevation myocardial infarction (STEMI) is typically more severe than non-STEMI (NSTEMI). UL16-binding proteins (ULBPs), which are NKG2D ligands, can be expressed on the surface of stressed and activated cells, prompting these cells to generate microparticles (MPs). Consequently, MPs carrying ULBPs, particularly ULBP1 (ULBP1+ MPs), may be released into the bloodstream. This study aimed to investigate the association between ULBP1+ MPs and the presence of AMI and its severity. We recruited 58 AMI patients and 45 age-matched control subjects. Levels of ULBP1+ MPs and ULBP1+ MPs originating from T lymphocytes (ULBP1+ TMPs) were measured using flow cytometry. Both ULBP1+ MP and ULBP1+ TMP levels were significantly elevated in AMI patients compared to controls. Elevated levels of these MPs were independent risk factors for AMI with odds ratios (OR) of 4.3 (95%CI=1.5-12.3) for ULBP1+ MPs and 5.8 (95%CI=2.0-17.0) for ULBP1+ TMPs. Additionally, ULBP1+ TMP levels were significantly higher in STEMI patients compared to NSTEMI patients, with an independent association observed between ULBP1+ TMPs and STEMI (OR=3.9; 95%CI=1.2-12.8). Elevated levels of ULBP1+ MPs and ULBP1+ TMPs are associated with AMI and its severity. These biomarkers could serve as indicators of vulnerable plaques that lead to AMI.

Loneliness in the elderly and disease development in European welfare regions: a longitudinal study

Abstract Healthy ageing research has brought a recent focus on the association between loneliness and disease. Regional differences on loneliness prevalence in the elderly across welfare systems, and its association with varying mortality rates, have recently been demonstrated. We hypothesise loneliness affects disease development in the elderly, impacted by socio-economic policies that characterise welfare systems in the EU. We use logistic regression models to assess the association between loneliness (R-UCLA scale) and onset of new chronic disease and disease events, in a European sample of people aged &amp;gt;50 (n = 40840), using the SHARE database, during 2013 - 22 (waves 5 to 9). Preliminary results from two subsequent waves (2015-17, n = 11870) show a statistically significant effect of persistent loneliness on disease onset (increase in new disease events), when adjusting for sex, age, previous illness, and other socio-economic covariates (AOR 1.22, 95%CI 1.08-1.39, p &amp;lt; 0.01). Notably, comparing to the Scandinavian welfare group, only Eastern European countries show higher odds of disease development (AOR 1.52, 95%CI 1.32-1.77, p &amp;lt; 0.001), while also having the highest incidence of new disease in our sample. Age and welfare group show the strongest association with the outcome of interest, followed by change in occupation (no longer employed). Our current analyses span a larger period (2013-22), and we are exploring additional mediators of this effect, such as behavioural and social activity-related variables. Additional analyses to control for unrelated disease (low biological plausibility) and a social isolation index, described in the literature, are added. Furthermore, we analyse the longitudinal association between loneliness and healthcare use, such as polypharmacy and consults. With this study, we aim to contribute decision-making in health in all policies, by increasing integration between health and social sectors, while considering different regional and welfare policies. Key messages • Understanding socio-economic and welfare mechanisms which impact health in the elderly allows for better cross-sector policy design, promoting healthier ageing. • Persistent feelings of loneliness affect disease development in the elderly, which appear to be worsened in some EU welfare groups, independently of socio-economic status.

Intracranial inoculation rapidly induces Nipah virus encephalitis in Syrian hamsters.

Nipah virus (NiV) is a highly pathogenic Paramyxovirus associated with outbreaks in Malaysia, Bangladesh, and India with high mortality rates. NiV infection causes fatal respiratory and neurological disease. The majority of survivors suffer from long-term neurological sequelae or late onset and relapsed encephalitis. The pathogenesis of neurological disease is complex and has not been able to be studied in current animal models as they are skewed towards the development of lethal respiratory disease rather than neurological disease. Although NiV neurological disease can be observed in animal models, there is currently no model where the majority of animals consistently develop neurological disease. Here, we developed a new Syrian hamster (Mesocricetus auratus) model to mimic neurological disease in humans. Hamsters were inoculated intracranially in the cerebellomedullary cistern with different doses of NiV, strain Malaysia. Intracranial NiV inoculation in the cerebellomedullary cistern resulted in a rapid progression towards severe neurological disease requiring euthanasia. High Nipah viral loads were detected in the brains, and NiV spread from the CNS to the lungs. Histopathologic examination of the brain showed ischemic necrosis, often accompanied by marked edema and hemorrhage. NiV antigen was detected primarily in meninges and cerebellum, but rarely observed in brain parenchyma. These histological lesions were different from the typical lesions observed in NiV-infected humans. Thus, despite the consistent development of neurological disease, intracranial inoculation does not result in a model representative of NiV neurological disease.

Nutrition of children up to one year of age what public health topic

Abstract Background Nutrition is one of the most important factors for a person that affects the quality and length of life. Nutrition has a fundamental influence on the maintenance of health or the development of disease and participates in the correct growth and development of an individual. Nutrition is especially important in the early stages of life, when a child’s organism develops dramatically. Mothers have the greatest influence on a child’s nutrition, and therefore it is advisable to educate them appropriately and also educate them early, from child birth or before. And early nutrition is provided through breastfeeding. Objectives To improve the knowledge of healthcare workers in the field of breastfeeding and nutrition of children up to one year of age. To strengthen the breastfeeding skills of mothers. To motivate healthcare workers to educate mothers in maternity wards and GP offices. Results Using a questionnaire, we analyzed the knowledge of 716 mothers of children under two years of age. 91 % of female respondents knew that the child should be breastfed according to his/her needs. Only 66 % of women were educated and informed about the importance and technique of breastfeeding. Educational material was prepared and distributed for midwives, nurses and doctors on breastfeeding and feeding children up to one year of age. Conclusions The level of awareness of health professionals about breastfeeding and nutrition is still insufficient. There is a need to continue to educate and support healthcare workers in this area and to motivate them in providing information to mothers. Key messages • Breastfeeding and feeding children up to one year of age are important for a child’s health. • The advisory activity of healthcare workers is key to improving public health. Health workers should help mothers not only with advice but also with practical help with breastfeeding.

Efficacy of using grape cane extracts against &lt;i&gt;Plasmopara viticola&lt;/i&gt; under field conditions and their impact on the composition of berries and musts of &lt;i&gt;Vitis vinifera&lt;/i&gt; L. cv. Riesling

Grapevine downy mildew caused by Plasmopara viticola is a deleterious vine disease currently controlled using synthetic and copper-based fungicides. Environmental concerns surrounding such fungicides necessitate sustainable alternatives like grape cane extracts. However, studies into their efficacy and effects on the product remain limited. This study aimed to assess the open-field efficacy of a novel grape cane extract formulation, alone and combined with a copper agent, against downy mildew, and to examine its impact on berry and must composition. The results were compared to standard fungicides frequently used in integrated and organic viticulture. In 2022, the grape cane extract formulation reduced downy mildew severity by 78 % on berry clusters, comparable to the maximum acceptable dose of copper for organic farming in Germany (3 kg/ha/a). Combining the grape cane extract with the copper agent was more effective than the copper agent alone, but not more effective than the grape cane extract alone. In 2023, disease development was marginal, despite artificial inoculation. Compositional differences detectable by FTIR were insignificant between musts derived from all treatments, increased copper levels were observed whenever copper had been applied. The phenolic content in freeze-dried, de-seeded berries of 2022 was significantly lower after copper (14.6 mg/g dry weight DW) and grape cane extract treatments (6.6 mg/g DW) when compared to the control (36.1 mg/g DW), with discrepancies in stilbenoid and flavan-3-ol levels in particular, as analysed by HPLC-DAD. However, these differences were not confirmed in 2023, with results showing no correlations between different treatments and phenolic contents. These findings suggest that applications of the phenolic grape cane extract do not lead to artificially altered levels or relevant residues of the active constituents; i.e., the phenolic compounds in the product. In brief, grape cane extracts might represent a promising natural alternative to controlling grapevine downy mildew, particularly in organic viticulture, which, to date, heavily relies on (eco-)toxic copper-pesticides. Further multi-year studies including wine analyses are warranted to follow the entire flow towards the final product.

Sex differences in proteomics of cardiovascular disease: results from the Yale-CMD registry

Abstract Background Cardiovascular disease is the leading cause of death globally, with notable sex differences in its presentation, mechanisms, and outcomes. Purpose We investigated the serum proteomic profiles of coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) patients to uncover sex-specific biological pathways and their roles in disease development. Methods Using the Yale-CMD registry's biobank, we performed a secondary analysis on adults with ischemic symptoms who underwent cardiac PET/CT and were not experiencing myocardial infarction, hemodynamic instability, acute heart failure, febrile illness, dialysis, or consent incapacity. Using PET/CT, we classified participants as controls (normal coronary flow reserve [CFR], no perfusion defect or coronary calcification), CAD (if new perfusion defect or known revascularization), or CMD (CFR &amp;lt;2 without defect or calcification). Using proximity extension assays (Olink® Explore 3072) in high-throughput proteomic analysis, we examined 2944 plasma proteins. Differential protein abundance analysis was performed using linear regression models adjusting for age, race, body mass index, history of diabetes, dyslipidemia, hypertension, and smoking to detect significant changes in protein abundance, with false discovery rate (FDR) control. Functional pathway analyses were conducted to identify the biological functions of the sex-differentially expressed proteins. Results Between 2014-2020, 91 patients of 190 in the registry provided blood samples for this analysis. Participants had median age 56.0 (50.0 - 62.0) years with 66% females. Among these, 48% were controls, 24% had CAD and 27% had CMD. Using linear regression adjusting for confounders, we identified significant sex differences in protein levels related to reproductive functions across all 3 cohorts (Fig. 1). In the CAD cohort, FSHB was upregulated in females, while INSL3 and EDDM3B were upregulated in males (FDR &amp;lt; 0.05). In the CMD cohorts, 6 proteins were differentially expressed (FDR &amp;lt; 0.05), with SCGB3A1 and HGFAC higher in females, and INSL3, SPINT3, EDDM3B, and KLK3 higher in males. Pathway analysis revealed that among patients with CAD, females had upregulation in immune system processes (Fig. 2A), while males showed upregulation of proteins related to endothelial regulation of blood flow (Fig. 2B). Among patients with CMD, females showed upregulation of lipid and glucose metabolism (Fig. 2C), while males showed upregulation of angiogenesis-related proteins (Fig. 2D). Conclusion We demonstrated significant sex differences in proteomic profiles among patients with CAD and CMD, underscoring the potential importance of sex-specific pathways in the pathophysiology of CVD. Our finding supports a need for large-scale validation studies to develop sex-tailored therapeutic strategies and advance precision medicine in cardiovascular health.Differential protein expression by sexPathway overrepresentation

Integrity of central nervous autonomous tracts is associated with cardiac function, cardiovascular risk factors, organ damage and major adverse cardiovascular events

Abstract Background Alterations in the central autonomic nervous system have been linked to the pathogenesis of cardiovascular (CV) risk and disease. Moreover, these conditions are treatable by pharmacological or interventional modification of the activity of the autonomic nervous system. Purpose The UK Biobank enables the investigation of the relationship between changes in the CAN and CV function or disease within a large population. Microstructural integrity of the CAN was assessed for associations with cardiac function, CV risk and damage representations, and major adverse cardiovascular events (MACE). Method Microstructural diffusion metrics for 7 CAN tracts were estimated using a Bayesian approach, which determines the three components of a standard white matter-based tissue model: 1. the free water fraction (CSF); 2. the fraction within neuronal processes, i.e. axons and dendrites (INTRA); and 3. the fraction outside of axons or dendrites (EXTRA), representing the cellular compartment and the extracellular matrix. Volume fractions of the three microstructural components were analysed for associations with cardiac index, blood pressure, CV target organ damage (arterial stiffness, left ventricular mass, and wall thickness), and MACE, using covariate-adjusted regression models that corrected for multiple comparisons. Results Analysis of cardiac function in 26,302 participants revealed significant associations between cardiac index and CAN regions in the cortical and subcortical networks. Arterial stiffness was significantly associated with markers of microstructural integrity in the cortical networks only (n=22,491), while systolic (n=34,114) and diastolic blood pressure (n=34,130), left ventricular mass (n=22,491) and wall thickness (n=22,491) showed extensive associations with the cortical and subcortical CAN. MACE (n=33,444) was associated with cortical markers of microstructural integrity of the CAN in limbic pathways (significant CANs all p&amp;lt;0.002) and the CAN pathways connecting cortical areas (significant CANs left all &amp;lt;0.001, right=0.001). The observed pattern of microstructural metrics suggests that the integrity of neural connections (intra-fraction) positively correlates with adverse outcomes, while an increase in free fluid (CSF) volume was typically associated with a negative impact. Conclusion In this analysis, markers of CAN integrity and degradation showed extensive associations with indicators of CV function, risk factors, damage parameters, and outcomes. This evidence supports the crucial role of autonomic regulation in cardiovascular disease. Future research is needed to determine whether these associations indicate harmful processes, such as neuroinflammation, contributing to cardiovascular (CV) risk and disease development, or if they are consequences of pre-existing elevated risk factors or events.CANs associated with MACEAssociations of CAN with CV organ damage