Benefits of an Adjustable Compression Garment System for the Reduction of Chronic Leg Oedema (ACROE Study).

OBJECTIVE: This study aimed to assess whether a specific adjustable compression garment (ACG) system (Coolflex Standard Calf and Coolflex Standard Foot; Sigvaris Inc.) promotes self-care in patients with chronic leg oedema. Secondary aims were to assess the effectiveness of this ACG in reducing oedema, improving patient reported outcomes, and determining the patients' degree of satisfaction with the handling of the wrap. METHODS: This was a multicentre prospective observational study. The study included 99 adult patients aged 18 - 90 years presenting with chronic oedema of the lower extremity, which encompasses conditions such as lymphoedema, venous oedema, and phlebolymphoedema. At baseline, all patients received an ACG. After two to three days and after six weeks, their overall satisfaction with the therapy was assessed. Leg volume was determined in a contactless manner during the baseline and follow up visits. All patients completed the cross cultural adaptation of the Lymphoedema Functioning, Disability and Health Questionnaire for Patients with Lymphoedema of the Lower Extremity in Germany (Lymph-ICF-UG). RESULTS: A total of 86 patients completed the study and were followed up for six weeks. At the final six week follow up, 82 (95.3%) of the 86 subjects indicated that they were able to put on the wrap independently or with a little help from relatives. The overall satisfaction rate was 88.0% (95% confidence interval [CI], 79.64 - 93.9%). The mean leg volume reduction from baseline to six weeks was -4.7% (95% CI -6.3 - -3.0%; p < .001). Lymph-ICF-UG scores and scores in all domains improved significantly from baseline to the final follow up. CONCLUSION: The ACG used in this study was found to promote self-care in a high proportion of patients with chronic leg oedema. A significant reduction in oedema was observed.

Risk factors for recognized and unrecognized SARS-CoV-2 infection: a seroepidemiologic analysis of the Prospective Urban Rural Epidemiology (PURE) study.

There are limited data on individual risk factors for SARS-CoV-2 infection (including unrecognized infection). In this seroepidemiologic substudy of an ongoing prospective cohort study of community-dwelling adults, participants were thoroughly characterized pre-pandemic. The SARS-CoV-2 infection was ascertained by serology. Among 8,719 participants from 11 high-, middle-, and low-income countries, 3,009 (35%) were seropositive for SARS-CoV-2. Characteristics independently associated with seropositivity were younger age (odds ratio, OR; 95% confidence interval, CI, per five-year increase: 0.95; 0.91-0.98) and body mass index >25 kg/m2 (OR, 95% CI: 1.16, 1.01-1.34). Smoking (as compared with never smoking, OR, 95% CI: 0.83, 0.70-0.97) and COVID-19 vaccination (OR, 95% CI: 0.70, 0.60-0.82) were associated with a reduced risk of seropositivity. Among seropositive participants, 83% were unaware of having been infected with SARS-CoV-2. Seropositivity and a lack of awareness of infection were more common in lower-income countries. The COVID-19 vaccination reduces the risk of SARS-CoV-2 infection (including recognized and unrecognized infections). Overweight or obesity is an independent risk factor for SARS-CoV-2 infection. Infection and lack of infection awareness are more common in lower-income countries.IMPORTANCEIn this large, international study, evidence of SARS-CoV-2 infection was obtained by testing blood specimens from 8,719 community-dwelling adults from 11 countries. The key findings are that (i) the large majority (83%) of community-dwelling adults from several high-, middle-, and low-income countries with blood test evidence of SARS-CoV-2 infection were unaware of this infection-especially in lower-income countries; and (ii) overweight/obesity predisposes to SARS-CoV-2 infection, while COVID-19 vaccination is associated with a reduced risk of SARS-CoV-2 infection. These observations are not attributable to other individual characteristics, highlighting the importance of the COVID-19 vaccination to prevent not only severe infection but possibly any infection. Further research is needed to understand the mechanisms by which overweight/obesity might increase the risk of SARS-CoV-2 infection.

Diagnostic criteria for Buerger's disease: International Consensus of VAS - European Independent Foundation in Angiology/Vascular Medicine.

Buerger's disease (BD) remains a debilitating condition and early diagnosis is paramount for its effective management. Despite many published diagnostic criteria for BD, selective criteria have been utilized in different vascular centers to manage patients with BD worldwide. A recent international Delphi Consensus Study on the diagnostic criteria of BD showed that none of these published diagnostic criteria have been universally accepted as a gold standard. Apart from the presence of smoking, these published diagnostic criteria have distinct differences between them, rendering the direct comparison of patient outcomes difficult. Hence, the expert committees from the Working Group of the VAS-European Independent Foundation in Angiology/Vascular Medicine critically reviewed the findings from the Delphi study and provided practical recommendations on the diagnostic criteria for BD, facilitating its universal use. We recommend that the 'definitive' diagnosis of BD must require the presence of three features (history of smoking, typical angiographic features and typical histopathological features) and the use of a combination of major and minor criteria for the 'suspected' diagnosis of BD. The major criterion is the history of active tobacco smoking. The five minor criteria are disease onset at age less than 45 years, ischemic involvement of the lower limbs, ischemic involvement of one or both of the upper limbs, thrombophlebitis migrans and red-blue shade of purple discoloration on edematous toes or fingers. We recommend that a 'suspected' diagnosis of BD is confirmed in the presence of a major criterion plus four or more minor criteria. In the absence of the major criterion or in cases of fewer than four minor criteria, imaging and laboratory data could facilitate the diagnosis. Validation studies on the use of these major and minor criteria are underway.

Is elevated ENA-78 serum level a link between obstructive sleep apnea and atherosclerosis?

Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease, inflammation, and oxidative stress. This study compared serum levels of different factors in patients with carotid artery stenosis and with or without coexisting OSA. It also aimed to identify a molecule that may be crucial for the inflammatory process correlated with intermittent hypoxia. Sixty-eight subjects scheduled for surgical treatment of carotid artery stenosis were enrolled. Polygraphy was performed the night before the surgery. Morning levels of proinflammatory cytokines and chemotactic and angiogenic factors were measured. The most profound differences between the groups were found for ENA-78 serum concentration. However, as many factors could affect the results, further studies are needed to investigate the role of ENA-78 in atherosclerosis in patients suffering from OSA.

Lymphoscintigraphic alterations in lower limbs in women with lipedema in comparison to women with overweight/obesity.

Introduction: Lipedema is a bilateral enlargement of the legs due to abnormal depositions of subcutaneous fat. Recent studies using lymphoscintigraphy documented that lipedema associates with lymphatic alterations. It is still not known, whether non-lipedema obesity also leads to similar lymphoscintigraphic changes within lower legs. Clinically, both, lipedema and obesity may progress to secondary lymphedema. The aim of the study was to evaluate lymphoscintigraphy of lower limbs in women with lipedema in comparison to overweight/obese women. Methods: 51 women (in the mean age of 43.3 ± 13.56) with the diagnosis of lipedema and 31 women (in the mean age of 44.7 ± 13.48) with overweight/obesity were enrolled into the study. Women in both study groups had no clinical signs of lymphedema. The groups were matched by mean volume of their legs, calculated using the formula for a truncated cone. Lymphoscintigraphy was evaluated in every women qualitatively. Body composition parameters were assessed using bioelectric impedance analysis (BIA). Results: Lymphoscintigraphic alterations within lower extremities were similar in both, lipedema and overweight/obese groups and were present in majority of women in both study groups. The most common lymphoscintigraphic alteration in both groups were additional lymphatic vessels (in the lipedema group observed in 76.5% of patients and in the overweight/obesity group - in 93.5%). Visualization of popliteal lymph nodes and dermal backflow were observed respectively in 33% and in 5.9% in the group with lipedema and in 45.2% and in 9.7% in the overweight/obesity group. There were significant relationships between severity of lymphoscintigraphic alterations and weight, lean body mass (LBM), total body water (TBW), volume of both legs and thigh circumference in the lipedema group. Such relationships were absent in the overweight/obesity group. Discussion: Our study indicates that lymphatic alterations are present before development to clinically visible secondary lymphedema in both conditions, lipedema and overweight/obesity. In majority of women from both study groups they indicate rather an overload of the lymphatic system than insufficiency. Lymphoscintigraphic alterations are similar in both groups, therefore, lymphoscintigraphy is not a diagnostic tool that might distinguish lipedema from overweight/obesity.

Asymmetric Dimethylarginine in an NMU-induced Rat Mammary Tumor Model.

BACKGROUND/AIM: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) production and a newly discovered risk factor involved in endothelial dysfunction and adverse cardiovascular events. Recently, both NO and ADMA have also emerged as molecules of interest in carcinogenesis and tumor growth progression. Our earlier studies have confirmed elevated plasma ADMA levels in patients with hematological malignancies. However, the cause of elevated ADMA was unclear. The aim of this study was to assess the concentrations of ADMA, symmetric dimethylarginine (SDMA) and L-arginine in rats exposed to N-nitroso-N-methylurea (NMU) for the induction of mammary tumors. MATERIALS AND METHODS: A total of 95 female rats of the Sprague-Dawley strain were used in the study. Plasma concentrations of ADMA, SDMA and L-arginine were quantified and statistically analyzed. RESULTS: Mean ADMA levels were higher in the tumor-bearing group compared to the control group. Mean plasma levels of SDMA and L-Arginine were not significantly different between the groups. The L-ARG/ADMA ratio was lower in rats with tumors compared to controls. CONCLUSION: Histological assessment confirmed expression of ADMA within the tumor cells, which strongly suggests that these tumor cells were the source of ADMA. Other studies are warranted to further explain the role of ADMA in neoplastic diseases.

Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study.

BACKGROUND & AIMS: Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and the risk of developing IBD using the Prospective Urban Rural Epidemiology cohort. METHODS: This was a prospective cohort study of 133,137 individuals between the ages of 20 and 80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed up prospectively at least every 3 years. The main outcome was the development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aORs) with 95% CIs. RESULTS: During a median follow-up period of 11.0 years (interquartile range, 9.2-12.2 y), there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was associated significantly with baseline antibiotic (aOR, 2.81; 95% CI, 1.67-4.73; P = .0001) and hormonal medication use (aOR, 4.43; 95% CI, 1.78-11.01; P = .001). Among females, previous or current oral contraceptive use also was associated with IBD development (aOR, 2.17; 95% CI, 1.70-2.77; P < .001). Nonsteroidal anti-inflammatory drug users also were observed to have increased odds of IBD (aOR, 1.80; 95% CI, 1.23-2.64; P = .002), which was driven by long-term use (aOR, 5.58; 95% CI, 2.26-13.80; P < .001). All significant results were consistent in direction for CD and UC with low heterogeneity. CONCLUSIONS: Antibiotics, hormonal medications, oral contraceptives, and long-term nonsteroidal anti-inflammatory drug use were associated with increased odds of incident IBD after adjustment for covariates.

An International Delphi Consensus on Diagnostic Criteria for Buerger's Disease.

BACKGROUND: Buerger's disease (BD) remains a debilitating condition. Despite multiple published diagnostic criteria for BD, none is universally accepted as a gold standard. METHODS: We conducted a 2-round modified Delphi consensus study to establish a consensus on the diagnostic. The questionnaire included statements from several commonly used diagnostic criteria for BD. Qualitative and quantitative analysis methods were performed. An agreement level of 70% was applied. RESULTS: Twenty nine experts from 18 countries participated in this study. Overall, 75 statements were circulated in Round 1. Of these, 28% of statements were accepted. Following comments, 21 statements were recirculated in Round 2 and 90% were accepted. Although more than 90% of the experts did not agree that the diagnosis of BD can be based only on clinical manifestation, none of the nonclinical manifestations of BD were agreed as a part of the diagnostic criteria. There was an agreement that a history of tobacco consumption in any form, not necessarily confined to the current use, should be a part of the diagnostic criteria of BD. The history of thrombophlebitis migrans, even if not present at presentation, was accepted as a clue for BD diagnosis. It was also agreed that discoloration of the toes or fingers could be included in the diagnostic criteria of BD. Experts agreed that histology results could differentiate BD from atherosclerosis obliterans and other types of vasculitis. The presence of corkscrew collaterals on imaging and burning pain reached the agreement at the first round but not at the second. There was no consensus regarding age cut-off, the requirement of normal lipid profile, and normal blood glucose for BD diagnosis. CONCLUSIONS: The present study demonstrated discrepancies in the various published diagnostic criteria for BD and their selective utilization in routine clinical practice worldwide. We propose that all published diagnostic criteria for BD be re-evaluated for harmonization and universal use.

Cardiovascular Risk Factors Drive Impaired Fasting Glucose to Type 2 Diabetes: Findings After a 9-Year Follow-Up in the PURE Study in Poland.

This study aimed to evaluate the role of risk factors included in the Framingham Risk Score for hard coronary heart disease (CHD) in the development of type 2 diabetes (DM) in patients with impaired fasting glycemia (IFG) after a 9-year follow-up. The research was part of the Polish insight into the international Prospective Urban and Rural Epidemiology (PURE) study. The cohort consisted of 283 subjects aged 54.3 ± 8.9 years who were diagnosed with IFG at baseline and then completed after a 9-year follow-up. The main risk factors for both CHD and DM evaluated were smoking, arterial hypertension, abnormal lipid profile, and family medical history. Most participants had both untreated or poorly controlled hypertension and dyslipidemia. Those who developed full-fledged DM over time were older and had significantly higher levels of fasting plasma glucose, lipid parameters, and mean blood pressure records. In conclusion, we confirmed that early diagnosis of dyslipidemia and hypertension, along with the treatment optimization of these conditions, could prevent or reduce the risk of DM and adverse cardiovascular outcomes. The study highlighted a large-scale problem of the modifiable risk factors that could jeopardize the health status in patients with IFG in the long range and pointed to targeted preventive measures.

Variations in the association of height with mortality, cardiovascular disease and cancer in low-, middle- and high-income countries.

BACKGROUND: Final adult height is a useful proxy measure of childhood nutrition and disease burden. Tall stature has been previously associated with decreased risk of all-cause mortality, decreased risk of major cardiovascular events and an increased risk of cancer. However, these associations have primarily been derived from people of European and East Asian backgrounds, and there are sparse data from other regions of the world. METHODS: The Prospective Urban-Rural Epidemiology study is a large, longitudinal population study done in 21 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years. Height was measured in a standardized manner, without shoes, to the nearest 0.1 cm. During a median follow-up of 10.1 years (interquartile range 8.3-12.0), we assessed the risk of all-cause mortality, major cardiovascular events and cancer. RESULTS: A total of 154 610 participants, enrolled since January 2003, with known height and vital status, were included in this analysis. Follow-up event data until March 2021 were used; 11 487 (7.4%) participants died, whereas 9291 (6.0%) participants had a major cardiovascular event and 5873 (3.8%) participants had a new diagnosis of cancer. After adjustment, taller individuals had lower hazards of all-cause mortality [hazard ratio (HR) per 10-cm increase in height 0.93, 95% confidence interval (CI) 0.90-0.96] and major cardiovascular events (HR 0.97, 95% CI 0.94-1.00), whereas the hazard of cancer was higher in taller participants (HR 1.23, 95% CI 1.18-1.28). The interaction p-values between height and country-income level for all three outcomes were <0.001, suggesting that the association with height varied by country-income level for these outcomes. In low-income countries, height was inversely associated with all-cause mortality (HR 0.88, 95% CI 0.84-0.92) and major cardiovascular events (HR 0.87, 95% CI 0.82-0.93). There was no association of height with these outcomes in middle- and high-income countries. The respective HRs for cancer in low-, middle- and high-income countries were 1.14 (95% CI 0.99-1.32), 1.12 (95% CI 1.04-1.22) and 1.20 (95% CI 1.14-1.26). CONCLUSIONS: Unlike high- and middle-income countries, tall stature has a strong inverse association with all-cause mortality and major cardiovascular events in low-income countries. Improved childhood physical development and advances in population-wide cardiovascular treatments in high- and middle-income countries may contribute to this gap. From a life-course perspective, we hypothesize that optimizing maternal and child health in low-income countries may improve rates of premature mortality and cardiovascular events in these countries, at a population level.

Assessment of Serum Neopterin as a Biomarker in Peripheral Artery Disease.

Neopterin (NPT), a pyrazino-pyrimidine compound mainly produced by activated macrophages, has been regarded as a proinflammatory and proatherosclerotic agent. The study was designed to evaluate NPT level and its interaction with conventional peripheral artery disease (PAD) biomarkers and vascular regenerative potential in severe PAD. The study included 59 patients (females n = 17, males n = 42) aged 67.0 ± 8.2 years classified into two groups based on ankle-brachial index (ABI) measurements (ABI ≤ 0.9 n = 43, ABI ≤ 0.5 n = 16). A total of 60 subjects aged 70.4 ± 5.5 years (females n = 42, males n = 18) with ABI > 0.9 constituted a reference group. NPT concentration reached values above 10 nmol/L in patients with PAD, which differed significantly from reference group (8.15 ± 1.33 nmol/L). High levels of CRP > 5 mg/L, TC > 200 mg/dL as well as lipoproteins LDL > 100 mg/dL and non-HDL > 130 mg/dL were found in the same group, indicating the relationship between NPT and conventional atherogenic markers. The endothelial progenitor cells (EPCs) tended toward lower values in patients with ABI ≤ 0.5 when compared to reference group, and inversely correlated with NPT. These findings indicate a crucial role of NPT in atheromatous process and its usefulness in monitoring PAD severity. However, the role of NPT in chronic PAD needs further studies including relatively high number of subjects.

The Impact of Common Epidemiological Factors on Gray and White Matter Volumes in Magnetic Resonance Imaging-Is Prevention of Brain Degeneration Possible?

Introduction: The aim of the study was to evaluate the impact of multiple risk factors (age, diabetes, hypertension, hyperlipidemia, BMI, smoking, alcohol) on the gray and white matter volumes as well as on the burden of white matter hyperintensities (WMH). Material and Methods: The study group consisted of 554 subjects (age range: 50-69 yrs, F/M: 367/187) recruited from the larger cohort of the Polish fraction of the Prospective Urban Rural Epidemiological (PURE) study. The participants answered questionnaires about their lifestyle, underwent physical and psychological examination (MoCA test), laboratory blood tests followed by brain MRI. Volumetric measurements of the total gray matter (GMvol), total white matter (WMvol) and WHM (WMHvol) normalized to the total intracranial volume were performed using the Computational Anatomy Toolbox 12 (CAT12) and Statistical Parametric Maps 12 (SPM12) based on 3D T1-weighted sequence. The influence of risk factors was assessed using multiple regression analysis before and after correction for multiple comparisons. Results: Older age was associated with lower GMvol and WMvol, and higher WMHvol (p < 0.001). Smaller GMvol volume was associated with higher WMHvol (p < 0.001). Higher WMHvol was associated with hypertension (p = 0.01) and less significantly with hyperlipidemia (only before correction p = 0.03). Diabetes, abnormal BMI, smoking and alcohol intake did not have any significant impact on GMvol, WMvol or WMHvol (p > 0.05). MoCA score was not influenced by any of the factors. Conclusions: Gray matter loss is strongly associated with the accumulation of WMH which seems to be potentially preventable by maintaining normal blood pressure and cholesterol levels.

Co-occurrence of unclassified myeloproliferative neoplasm and giant cell arteritis in a patient treated with allogeneic hematopoietic stem cell transplantation: a case report and literature review.

Myeloproliferative neoplasms (MPNs) are a group of hematologic disorders characterized by clonal proliferation of myeloid lineage cells. The diagnostic criteria are based on morphological features of bone marrow and peripheral blood cells but also include specific genomic mutations. In some patients, co-occurrence of hematologic and rheumatic diseases could be observed. To date, most of the reported cases concerned patients with myelodysplastic syndrome (MDS) or essential thrombocythemia (ET). In this paper, we present a case of a patient with a complicated diagnostic process leading to the diagnosis of unclassified MPN and giant cell arteritis (GCA). Routine tests did not reveal any mutations typical for MPNs such as JAK-2, CALR, MPL or BCR-ABL. Targeted next-generation sequencing (NGS) helped to confirm the diagnosis by demonstrating the presence of heterozygous ASXL1, TET2, SRSF2, and CBL mutations. The second important issue was the overlapping of symptoms of MPN and seronegative rheumatic disease, which finally was diagnosed as GCA. Leukocytosis and musculoskeletal pain, which were present at the time of diagnosis, resolved after allogeneic hematopoietic stem cell transplantation but recurred after a few months along with decreasing donor cell chimerism. Differentiation of the causes of recurrence of the symptoms was an important issue. This case shows the diagnostic challenge posed by co-incidence of MPN and rheumatic disease, especially its atypical variants.

Impact of social isolation on mortality and morbidity in 20 high-income, middle-income and low-income countries in five continents.

OBJECTIVE: To examine the association between social isolation and mortality and incident diseases in middle-aged adults in urban and rural communities from high-income, middle-income and low-income countries. DESIGN: Population-based prospective observational study. SETTING: Urban and rural communities in 20 high income, middle income and low income. PARTICIPANTS: 119 894 community-dwelling middle-aged adults. MAIN OUTCOME MEASURES: Associations of social isolation with mortality, cardiovascular death, non-cardiovascular death and incident diseases. RESULTS: Social isolation was more common in middle-income and high-income countries compared with low-income countries, in urban areas than rural areas, in older individuals and among women, those with less education and the unemployed. It was more frequent among smokers and those with a poorer diet. Social isolation was associated with greater risk of mortality (HR of 1.26, 95% CI: 1.17 to 1.36), incident stroke (HR: 1.23, 95% CI: 1.07 to 1.40), cardiovascular disease (HR: 1.15, 95% CI: 1.05 to 1.25) and pneumonia (HR: 1.22, 95% CI: 1.09 to 1.37), but not cancer. The associations between social isolation and mortality were observed in populations in high-income, middle-income and low-income countries (HR (95% CI): 1.69 (1.32 to 2.17), 1.27 (1.15 to 1.40) and 1.47 (1.25 to 1.73), respectively, interaction p=0.02). The HR associated with social isolation was greater in men than women and in younger than older individuals. Mediation analyses for the association between social isolation and mortality showed that unhealthy behaviours and comorbidities may account for about one-fifth of the association. CONCLUSION: Social isolation is associated with increased risk of mortality in countries at different economic levels. The increasing share of older people in populations in many countries argues for targeted strategies to mitigate its adverse effects.

Left ventricular myocardial strain assessed by cardiac magnetic resonance feature tracking in patients with rheumatoid arthritis.

PURPOSE: The aim of the study was to assess a relationship between the occurrence of rheumatoid arthritis (RA) and its selected clinical parameters, and left ventricular myocardial strain. MATERIAL AND METHODS: Fifty-six subjects were qualified for the study: 30 RA patients and 26 subjects without rheumatoid diseases. The study design included taking medical history, assessment of the disease activity using selected scales of activity, collecting samples of venous blood to assess selected laboratory parameters and the assessment of cardiac magnetic resonance (CMR). Using the feature tracking method, the following parameters of the left ventricular myocardial strain were assessed: longitudinal strain (LS), radial strain (RS) and circumferential strain (CS). RESULTS: Regarding global values, peak LS and peak CS were statistically significantly lower in RA patients than in the control group. In the whole study group, the factors independently related to low global LS peaks were as follows: occurrence of RA, occurrence of arterial hypertension, increased activity of antibodies against cyclic citrullinated peptide and increased concentration of neutrophil gelatinase-associated lipocalin. The occurrence of RA, occurrence of diabetes, tobacco smoking, higher activity of antibodies against cyclic citrullinated peptide and current use of methotrexate are the risk factors for low peak of global CS. The current use of steroids constitutes a protecting factor against low global CS peaks. CONCLUSION: In subjects with no clinically manifested cardiac damage, RA is associated with a deteriorated left ventricular systolic function assessed by left ventricular myocardial strain measured by CMR feature tracking.

"Cerebral small vessel disease and other influential factors of cognitive impairment in the middle-aged: a long-term observational cohort PURE-MIND study in Poland".

A complex picture of factors influencing cognition is necessary to be drawn for a better understanding of the role of potentially modifiable factors in dementia. The aim was to assess the prevalence and determinants of cognitive impairment, including the role of cerebral small vessel disease (CSVD) in Polish middle-aged cohort. A comprehensive set of clinical (hypertension, coronary heart disease, diabetes mellitus, hyperlipidaemia, body mass index, smoking status, alcohol intake) and socio-demographic data was collected in the PURE study in years 2007-2016, which was the basis for detailed analysis of risk factors of cognitive impairments in years 2016-2018 in the PURE-MIND sub-study. Five hundred forty-seven subjects (age range 39-65, mean 56.2 ± 6.5) underwent neuropsychological assessment with Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT) and Digit Symbol Substitution Test (DSST) followed by brain MRI. Mean MoCA score was 26.29 and 33% participants met criteria for mild cognitive impairment (MCI) (MoCA< 26). Seventy-three percent showed findings related to CSVD. Higher WMH burden and lacunar infarcts were associated with lower MoCA and DSST scores. Severe CSVD was associated with twofold incidence of MCI, and obesity increased its probability by 53% and hypertension by 37%. The likelihood of MCI was reduced in nonsmokers. One factor analysis showed the important role of lower level of education, older age, rural area of residence and hypertension. MCI and CSVD are highly prevalent in the middle-aged population in Poland. A greater importance should be given to potentially modifiable risk factors of dementia which are already present in mid-life.

Metabolomics of Interstitial Fluid, Plasma and Urine in Patients with Arterial Hypertension: New Insights into the Underlying Mechanisms.

There is growing evidence that lymphatic system plays a pivotal role in the pathogenesis of hypertension. Here, for the first time, the metabolome of interstitial fluid is analyzed in patients with arterial hypertension. Due to ethical issues to obtain human interstitial fluid samples, this study included only oncological patients after axillary lymph node dissection (ALND). These patients were matched into hypertensive (n = 29) and normotensive (n = 35) groups with similar oncological status. Simultaneous evaluation of interstitial fluid, plasma, and urine was obtained by combining high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy with chemometric analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) provided a clear differentiation between the hypertension and normotensive group, with the discrimination visible in each biofluid. In interstitial fluid nine potential metabolomic biomarkers for hypertension could be identified (creatinine, proline, pyroglutamine, glycine, alanine, 1-methylhistidine, the lysyl group of albumin, threonine, lipids), seven distinct markers in plasma (creatinine, mannose, isobutyrate, glycine, alanine, lactate, acetate, ornithine), and seven respectively in urine (methylmalonate, citrulline, phenylacetylglycine, fumarate, citrate, 1-methylnicotinamide, trans-aconitate). Biomarkers in plasma and urine allowed for the identification of specific biochemical pathways involved in hypertension, as previously suggested. Analysis of the interstitial fluid metabolome provided additional biomarkers compared to plasma or urine. Those biomarkers reflected primarily alterations in the metabolism of lipids and amino acids, and indicated increased levels of oxidative stress/inflammation in patients with hypertension.

Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries.

Importance: Depression is associated with incidence of and premature death from cardiovascular disease (CVD) and cancer in high-income countries, but it is not known whether this is true in low- and middle-income countries and in urban areas, where most people with depression now live. Objective: To identify any associations between depressive symptoms and incident CVD and all-cause mortality in countries at different levels of economic development and in urban and rural areas. Design, Setting, and Participants: This multicenter, population-based cohort study was conducted between January 2005 and June 2019 (median follow-up, 9.3 years) and included 370 urban and 314 rural communities from 21 economically diverse countries on 5 continents. Eligible participants aged 35 to 70 years were enrolled. Analysis began February 2018 and ended September 2019. Exposures: Four or more self-reported depressive symptoms from the Short-Form Composite International Diagnostic Interview. Main Outcomes and Measures: Incident CVD, all-cause mortality, and a combined measure of either incident CVD or all-cause mortality. Results: Of 145 862 participants, 61 235 (58%) were male and the mean (SD) age was 50.05 (9.7) years. Of those, 15 983 (11%) reported 4 or more depressive symptoms at baseline. Depression was associated with incident CVD (hazard ratio [HR], 1.14; 95% CI, 1.05-1.24), all-cause mortality (HR, 1.17; 95% CI, 1.11-1.25), the combined CVD/mortality outcome (HR, 1.18; 95% CI, 1.11-1.24), myocardial infarction (HR, 1.23; 95% CI, 1.10-1.37), and noncardiovascular death (HR, 1.21; 95% CI, 1.13-1.31) in multivariable models. The risk of the combined outcome increased progressively with number of symptoms, being highest in those with 7 symptoms (HR, 1.24; 95% CI, 1.12-1.37) and lowest with 1 symptom (HR, 1.05; 95% CI, 0.92 -1.19; P for trend < .001). The associations between having 4 or more depressive symptoms and the combined outcome were similar in 7 different geographical regions and in countries at all economic levels but were stronger in urban (HR, 1.23; 95% CI, 1.13-1.34) compared with rural (HR, 1.10; 95% CI, 1.02-1.19) communities (P for interaction = .001) and in men (HR, 1.27; 95% CI, 1.13-1.38) compared with women (HR, 1.14; 95% CI, 1.06-1.23; P for interaction < .001). Conclusions and Relevance: In this large, population-based cohort study, adults with depressive symptoms were associated with having increased risk of incident CVD and mortality in economically diverse settings, especially in urban areas. Improving understanding and awareness of these physical health risks should be prioritized as part of a comprehensive strategy to reduce the burden of noncommunicable diseases worldwide.

The Bioinformatic and In Vitro Studies of Clostridioides Difficile Aminopeptidase M24 Revealed the Immunoreactive KKGIK Peptide.

Clostridioides difficile (CD) is a Gram-positive pathogen responsible for CD-associated disease (CDAD), which is characterized by symptoms ranging from mild diarrhea to pseudomembranous colitis. This work is an attempt to respond to the need of novel methods for CD infection (CDI) prevention, since the number of CDI cases is still rising. A bioinformatics approach was applied to design twenty-one peptides consisting of in silico predicted linear B-cell and T-cell epitopes of aminopeptidase M24 from CD. These peptides were mapped for epitopes exploiting PEPSCAN procedure and using sera obtained from CD infected patients, umbilical cord blood, and healthy volunteers. Two new CD epitopes, 131KKGIK135 and 184KGTSTHVIT192, were identified and characterized. Immunoreactivity of the synthetic biotinylated 131KKGIK135 epitope was significantly higher compared to 184KGTSTHVIT192 epitope in Enzyme-Linked Immunosorbent Assay (ELISA) with umbilical cord blood and CDI patients' sera. Hereafter, the conjugate of bovine serum albumin and epitope 131KKGIK135 was evaluated in vitro on lung epithelial cell line. In vitro, a significant induction of IL-6 by conjugate was observed, thereby we postulate that this new 131KKGIK135 epitope possesses immunostimulating properties suggesting possibility of its use in a vaccine against Clostridioides difficile.

Association between dietary glycaemic load and selected demographic, socio-economic and lifestyle factors in a group of adult Poles in Lower Silesia - Results of the PURE Poland Study.

INTRODUCTION: There is a strong association between the occurrence of cardiovascular disease (CVD) and low socio-economic status (SES). It is interesting to consider whether high dietary glycaemic load (GL) is also associated with low SES or demographic factors. OBJECTIVE: The aim of the study is to assess the relationship between dietary GL and demographic, socio-economic and lifestyle factors in a selected population of Polish adults in Lower Silesia. MATERIAL AND METHODS: The study group consisted of 2,025 Polish adults (aged 35-70 years), enrolled in the 1st stage of the Prospective Urban Rural Epidemiological (PURE) study. Nutritional data were collected using a food frequency questionnaire (FFQ), which was developed and validated for the Polish population in Lower Silesia. The overall GL of each diet was computed as a sum of GL values of consumed foods. RESULTS: Significantly higher GL and GL/1,000 kcal were observed in the diets of males compared to females and in the diets of rural compared to urban inhabitants. An adverse relationship between both GL and GL/1,000 kcal and level of education was found. The percentage of females, urban inhabitants, people with university education and not married decreased with quartiles of the overall dietary GL and GL/1,000 kcal. The percentage of former smokers, people who never used alcohol and people with low and moderate physical activity decreased with quartiles of GL and GL/1,000 kcal. Lower percentage of individuals aged 44-64 years was observed with quartiles of the overall dietary GL. CONCLUSIONS: Factors such as: male gender, rural place of residence, low level of education and smoking determine the group of people that is the most exposed on the effects of improper nutrition, according to the low quality and/or high amount of carbohydrates defined by GL and GL per 1,000 kcal.