Advanced glycosylation end products as metabolic predictors of systemic pro-inflammatory and prooxidant status in patients with end-stage renal disease.

Controlling systemic proinflammatory and prooxidant effectors is essential for mitigating cardiovascular risk and mortality in patients with end-stage renal disease (ESRD). However, monitoring these processes is still challenging due to the high uncertainty about their determinants and predictors. Thus, we investigated the relationship between advanced glycosylation end products (AGE), proinflammatory and prooxidant effectors in ESRD patients undergoing hemodialysis (HD). In addition to nutritional profile and dialysis efficiency, AGE, cytokines, chemokines, C-reactive protein (CRP), total (TAC) and non-protein (npAC) antioxidant capacity, lipid and protein oxidation were analyzed in blood samples from 43 HD patients. AGE, CRP, cytokines, chemokines, protein carbonyl (PCn), and malondialdehyde (MDA) were upregulated, while TAC and npAC were down-regulated in HD patients compared to heath subjects. Dialysis efficiency, TAC and npAC were reduced, while leucocytes counting, pre- and post-HD urea, TNF, IL-6, IL-10, CCL-2, MIP-1ß, PCn, and MDA were increased in patients with higher AGE accumulation compared to those with lower AGE levels. Serum levels of CRP, protein carbonyl, malondialdehyde, and all cytokines and chemokines analyzed were correlated with AGE circulating levels for patients with higher AGE accumulation. AGE was inversely correlated with IL-10, TAC and npAC in patients with higher AGE accumulation. AGE exhibited predictive value (determination coefficient) to explain CRP, cytokines, chemokines, PCN, MDA, TAC and npAC variability in patients with higher AGE levels. Taken together, our findings provide evidence that AGE accumulation is associated with important proinflammatory and prooxidant effectors in patients with ESRD undergoing hemodialysis. Thus, AGE monitoring may be relevant to predict systemic inflammatory stress and the balance between oxidant and antioxidant status in these patients.

The Life with Corona survey.

The COVID-19 pandemic is a global crisis affecting everyone. Yet, its challenges and countermeasures vary significantly over time and space. Individual experiences of the pandemic are highly heterogeneous and its impacts span and interlink multiple dimensions, such as health, economic, social and political impacts. Therefore, there is a need to disaggregate "the pandemic": analysing experiences, behaviours and impacts at the micro level and from multiple disciplinary perspectives. Such analyses require multi-topic pan-national survey data that are collected continuously and can be matched with other datasets, such as disease statistics or information on countermeasures. To this end, we introduce a new dataset that matches these desirable properties - the Life with Corona (LwC) survey - and perform illustrative analyses to show the importance of such micro data to understand how the pandemic and its countermeasures shape lives and societies over time.

Relationship between time-dependent variability in cardiometabolic risk factors and biochemical markers with cytokine and adipokine levels in hemodialysis patients.

Hemodialysis patients (HP) are exposed to malnutrition, cardiometabolic and pro-inflammatory risk factors. However, limited knowledge of the variability of these risk factors remains a serious barrier to the proper clinical management of HP. From a longitudinal study, we investigated the relationship between time-dependent variability in cardiometabolic risk factors and biochemical markers with cytokine and adipokine circulating levels in HP. Thirty-eight HP (women = 15, men = 23) aged 54.13 ± 16.78 years old underwent three independent anthropometric, nutritional, biochemical and immunological assessments (1, 6 and 12 months). Patient's characteristics (body mass, comorbidities, history of kidney disease and time on hemodialysis) were similar after sex stratification. From grouped data, 31.6-100.0% HP exhibited multiple malnutrition and cardiometabolic risk factors in all time-points evaluated. All anthropometric and nutritional results, and most biochemical markers were similar in 1, 6 and 12 months follow-up, indicating a marked time-dependent stability. Urea, creatinine, total proteins, albumin, adipokines (adiponectin, leptin and resistin) and cytokines (TNF, IL-6 and IL-10) levels were highly variable in 12 months follow-up. Direct correlations between leptin and fat mass, TNF and IL-6 with creatinine and pre-dialysis urea were observed in all time-points (1, 6 and 12 months). Creatinine and pre-dialysis urea were negatively correlated with IL-10 for the entire follow-up. Fat mass, creatinine and pre-dialysis urea were predictive markers of leptin, TNF, IL-6 and IL-10 variability. Our findings indicated that biochemical, nutritional and cardiovascular risk factors exhibit low time-dependent variability in HP under clinical and nutritional monitoring. However, adipokines and cytokines are highly variables, which can potentially be influenced by body adiposity, creatinine and urea clearance. Thus, these parameters can contribute to predict the inflammatory status in HP.

Cytokines and chemokines systemic levels are related to dialysis adequacy and creatinine clearance in patients with end-stage renal disease undergoing hemodialysis.

Although the clearance of low-molecular weight toxins is modulated by dialysis dose, the relationship between dialysis adequacy and middle systemic inflammatory mediators is often overlooked. Thus, the relationship between dialysis adequacy, pro- and anti-inflammatory cytokines and chemokines in hemodialysis (HD) patients was investigated. Forty-eight HD patients (19 women and 25 men) were investigated. Age, body mass index, time in HD, nutritional status, Kt/V and blood biochemical parameters was similar in patients of both sexes (P > 0.05). Thus, patients were stratified by dialysis adequacy measured by Kt/V method (adequate Kt/V ≥ 1.2). Post-HD urea, creatinine, cytokines (IFN-γ, IL-4 and IL-10) and chemokines (CCL-2, CCL-5, CXCL-8 and CXCL-10) were higher in patients with Kt/V < 1.2 (P < 0.05). Kt/V exhibited significant correlation with CXCL-10/IP-10 serum levels. Positive correlation between creatinine with IFN-γ, CCL-2/MCP-1, and CXCL-10/IP-10, and negative correlation with IL-10 was identified in patients with Kt/V < 1.2 (P < 0.05). In patients with Kt/V ≥ 1.2, only IL-10 was positively and CXCL-10/IP-10 negatively correlated with creatinine levels (P < 0.05). Kt/V and creatinine levels exhibited variable predictive value (Kt/V = 27% to 37%, creatinine = 29% to 47%) to explain cytokines and chemokines circulating levels in patients with adequate and inadequate dialysis dose. Taken together, our findings provide evidence that in addition to modulating uremic toxins levels, such as urea and creatinine, dialysis dose is associated with circulating levels of inflammatory mediators. Thus, low Kt/V results and creatinine accumulation are potential indicators of the systemic inflammatory stress determined by up-regulation of proinflammatory cytokines and chemokines, and downregulation of anti-inflammatory cytokines.

Life With Corona: Increased Gender Differences in Aggression and Depression Symptoms Due to the COVID-19 Pandemic Burden in Germany.

Gender differences (GD) in mental health have come under renewed scrutiny during the COVID-19 pandemic. While rapidly emerging evidence indicates a deterioration of mental health in general, it remains unknown whether the pandemic will have an impact on GD in mental health. To this end, we investigate the association of the pandemic and its countermeasures affecting everyday life, labor, and households with changes in GD in aggression, anxiety, depression, and the somatic symptom burden. We analyze cross-sectional data from 10,979 individuals who live in Germany and who responded to the online survey "Life with Corona" between October 1, 2020 and February 28, 2021. We estimate interaction effects from generalized linear models. The analyses reveal no pre-existing GD in aggression but exposure to COVID-19 and COVID-19 countermeasures is associated with sharper increases in aggression in men than in women. GD in anxiety decreased among participants with children in the household (with men becoming more anxious). We also observe pre-existing and increasing GD with regards to the severity of depression, with women presenting a larger increase in symptoms during the hard lockdown or with increasing stringency. In contrast to anxiety, GD in depression increased among participants who lived without children (women > men), but decreased for individuals who lived with children; here, men converged to the levels of depression presented by women. Finally, GD in somatic symptoms decreased during the hard lockdown (but not with higher stringency), with men showing a sharper increase in symptoms, especially when they lived with children or alone. Taken together, the findings indicate an increase in GD in mental health as the pandemic unfolded in Germany, with rising female vulnerability to depression and increasing male aggression. The combination of these two trends further suggests a worrying mental health situation for singles and families. Our results have important policy implications for the German health system and public health policy. This public health challenge requires addressing the rising burden of pandemic-related mental health challenges and the distribution of this burden between women and men, within families and for individuals who live alone.

Political violence, adverse shocks and child malnutrition: Empirical evidence from Andhra Pradesh, India.

We analyze the combined effect of political violence and adverse climatic and health shocks on child nutrition using longitudinal data from Andhra Pradesh, India. The paper shows three key results using two-stage least square (2SLS) models: (i) the presence of political violence reduces the mean height-for-age z-scores of children by between 0.4 and 0.9 standard deviations and reduces the mean weight-for-age z-scores of children by between 0.3 and 0.6 standard deviations; (ii) political violence generates such a large negative effect on the long-term nutrition of children (measured by height-for-age z-scores) through a reduction of the ability of households to cope with drought and illness; and (iii) drought and illness have an adverse effect on child nutrition in Andhra Pradesh only in violence-affected communities. The 2SLS results are robust to a wide range of robustness tests. Potential mechanisms explaining the strong joint welfare effect of conflict and adverse shocks are the failure of economic coping strategies in areas of violence and restricted access to public goods and services.

Potential Role of Nutrient Intake and Malnutrition as Predictors of Uremic Oxidative Toxicity in Patients with End-Stage Renal Disease.

Oxidative stress is an important risk factor for cardiovascular disease and death in hemodialysis (HD) patients. However, whether biochemical and nutritional markers might be useful to stratify HD patients according to the risk of oxidative damage remains unclear. We investigated whether low-cost and easily available parameters such as the profile of nutrients intake, nutritional status, and antioxidant defenses can predict lipid and protein oxidation in HD patients. Forty-nine HD patients (women = 20, men = 29), ranging from 18 to 65 years of age (73.5%) were submitted to biochemical and nutritional analysis. At least 93.9% of HD patients had malnutrition. A patient's stratification according to nutritional risk was highly coherent with anthropometric parameters and nutrients intake, which were complementarily used as markers of malnutrition. Nutritional stratification was unable to reveal differences in the oxidative status. On the other hand, carbohydrate and zinc intake, serum zinc (Zn), glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC), and nonprotein antioxidants (npAC) in serum were predictive markers of lipid (R 2 = 0.588, P < 0.001) and protein (R 2 = 0.581, P < 0.001) oxidation. Interestingly, GPx activity, TAC, and npAC exhibited good (>80% < 90%) or excellent (>90%) accuracy to estimate lipid oxidation (P ≤ 0.01). Regarding the prediction of protein oxidation, GPx activity and TAC presented regular accuracy (>70% < 80%), and Zn serum levels exhibited good sensitivity (P ≤ 0.01). Herein, we provided evidence that clinical characteristics relevant to predict different levels of lipid and protein oxidation in HD patients can be easily obtained, during routine hospital visits by means of the combined analyses of biochemical and nutritional parameters.