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Considering the fact that Toxoplasma is a common parasite of humans and Toxoplasma bradyzoites can reside in skeletal muscle, T. gondii-mediated immune responses may modulate the progression and pathophysiology of another musculoskeletal disorder, osteoporosis. In the current study, we investigated the association of bone health and Toxoplasma gondii infection status. A total of 138 patients living in Germany with either osteopenia or osteoporosis were included in the study, and they were categorized into two groups, T. gondii uninfected (n = 74) and infected (n = 64), based on the presence of T. gondii-specific IgG antibodies. The demographic and clinical details of the study subjects were collected from the medical records. Logistic regression analysis was performed to delineate the association of bone health parameters with the infection status. The prevalence of toxoplasmosis was 46.4% in the study participants. The infected individuals with osteopenia and osteoporosis showed higher levels of mean spine and femoral T score, Z score, and bone mineral density (BMD), indicating improved bone health compared to the uninfected group. Logistic regression analysis showed that subjects with T. gondii infection displayed increased odds of having a higher mean femur T score, femur BMD, and femur Z score even after adjusting for age, creatinine, and urea levels. However, when the duration of drug intake for osteoporosis was taken into account, the association lost statistical significance. In summary, in this study, an improvement in osteopenia and osteoporosis was observed in Toxoplasma-infected patients, which may be partly due to the longer duration of drug intake for osteoporosis in the infected patient group.

BackgroundLife-style metabolic diseases are steadily rising, not only in developed countries, but also in low- and middle-income countries, presenting a global health problem. Metabolic disorders like type 2 diabetes and cardiovascular diseases are among the ten leading causes of death defined by the WHO in 2019. Results from animal and observational human studies suggest a connection between the decline in human helminth infections and rise of life-style-associated metabolic diseases in developing regions. This trial was designed to investigate filarial infections and their impact on metabolic diseases in Cameroon. We hypothesize that the induction of regulatory immune responses during filarial infection reduces obesity-induced low-grade inflammatory immune responses and thereby improves metabolic parameters, whereas anthelmintic treatment abolishes this protective effect.Methods/designParticipants infected with Mansonella perstans, Onchocerca volvulus and/or Loa loa being lean (BMI 25 and ConclusionThe focus of this study is to obtain a comprehensive metabolic profile of the participants in rural areas of Cameroon and to investigate the relationship between filarial immunomodulation and metabolic diseases. This study will elucidate the effect of anti-filarial treatment on the metabolic and immunological parameters that partake in the development of insulin resistance, narrowing in on a potential protective effect of filarial infections on metabolic diseases.Trial registrationdoi.org/10.1186/ISRCTN43845142, ISRCTN43845142 February 2020 Trial title Effects of filarial parasite infection on type 2 diabetes Issue date: 27.10.22, V.1.

Even after successful weight reduction, obese adults tend to quickly regain the lost weight. This raises the question of whether weight loss improves the underlying chronic adipose tissue inflammation characteristic of obesity. In order to improve our understanding of the mechanisms that reshape metabolic organs during weight loss, we investigated the macrophage and T cell function of the liver and adipose tissue on reversing high fat diet (HFD) mice to normal control diet (NCD). Obese mice that were switched to NCD showed an improvement in their metabolic profile that included enhanced glucose and insulin tolerance, decreased cholesterol, triglyceride, serum glutamic-oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT) levels that were comparable to NCD controls. However, despite weight loss, increased frequencies, but not total numbers, of IL-17+ and IL-22+ CD4+ T cells, IFN-γ+ and TNF+ CD8+ T cells and IL-17+ and IL-22+ CD8+ T cells were observed in the adipose tissue of mice switched from HFD to NCD compared to NCD and even HFD fed mice. Further, in the liver, IFN-γ+ and TNF+ CD8+ T cell, IL-17+ and IL-22+ CD8+ T cell, macrophage frequencies and their expression of antigen presenting molecules were increased. To determine if macrophages are the major determinants of the sustained inflammation observed during weight loss, we depleted macrophages, which significantly reduced IFN-γ+, TNF+, IL-17+, and IL-22+ CD8+ T cell frequencies in the liver and the adipose tissue. In conclusion, we show that although weight loss improves the metabolic profile, there is an active and ongoing CD8+ T cell inflammation in liver and adipose tissue mediated by macrophages.

Neutrophils are essentially involved in protective immune responses against invading infective larvae of filarial nematodes. The present study investigated the impact of S100A8/S100A9 on protective immune responses against the rodent filarial nematode Litomosoides sigmodontis. S100A9 forms with S100A8 the heterodimer calprotectin, which is expressed by circulating neutrophils and monocytes and mitigates or amplifies tissue damage as well as inflammation depending on the immune environment. Mice deficient for S100A8/A9 had a significantly reduced worm burden in comparison to wildtype (WT) animals 12 days after infection (dpi) with infective L3 larvae, either by the vector or subcutaneous inoculation, the latter suggesting that circumventing natural immune responses within the epidermis and dermis do not alter the phenotype. Nevertheless, upon intradermal injection of L3 larvae, increased total numbers of neutrophils, eosinophils and macrophages were observed within the skin of S100A8/A9-/- mice. Furthermore, upon infection the bronchoalveolar and thoracic cavity lavage of S100A8/A9-/- mice showed increased concentrations of CXCL-1, CXCL-2, CXCL-5, as well as elastase in comparison to the WT controls. Neutrophils from S100A8/A9-/- mice exhibited an increased in vitro activation and reduced L3 larval motility more effectively in vitro compared to WT neutrophils. The depletion of neutrophils from S100A8/A9-/- mice prior to L. sigmodontis infection until 5dpi abrogated the protective effect and led to an increased worm burden, indicating that neutrophils mediate enhanced protective immune responses against invading L3 larvae in S100A8/A9-/- mice. Interestingly, complete circumvention of protective immune responses in the skin and the lymphatics by intravenous injection of L3 larvae reversed the phenotype and resulted in an increased worm burden in S100A8/A9-/- mice. In summary, our results reveal that lack of S100A8/S100A9 triggers L3-induced inflammatory responses, increasing chemokine levels, granulocyte recruitment as well as neutrophil activation and therefore impairs larval migration and susceptibility for filarial infection.

Compared to the innate immune system, the contribution of the adaptive immune response during obesity and insulin resistance is still not completely understood. Here we demonstrate that high fat diet (HFD) increases the frequencies of activated CD4+ and CD8+ T cells and frequencies of T cells positive for IFN-γ and IL-17 in the adipose tissue. The adipocyte-derived soluble factor adiponectin reduces IFN-γ and IL-17 positive CD4+ T cells from HFD mice and dampens the differentiation of naïve T cells into Th1 cells and Th17 cells. Adiponectin reduces Th17 cell differentiation and restrains glycolysis in an AMPK dependent fashion. Treatment with adult worm extracts of the rodent filarial nematode Litomosoides sigmodontis (LsAg) reduces adipose tissue Th1 and Th17 cell frequencies during HFD and increases adiponectin levels. Stimulation of T cells in the presence of adipocyte-conditioned media (ACM) from LsAg-treated mice reduces Th1 and Th17 frequencies and this effect was abolished when ACM was treated with an adiponectin neutralizing antibody. Collectively, these data reveal a novel role of adiponectin in controlling pro-inflammatory CD4+ T cells during obesity and suggest that the beneficial role of helminth infections and helminth-derived products on obesity and insulin resistance may be in part mediated by adiponectin.

Aim: This study looked at the association of adipokines, inflammatory and oxidative stress markers in subjects with the following phenotypes: metabolically healthy, nonobese (MHNO), metabolically healthy, obese (MHO), metabolically obese, nonobese (MONO), and metabolically obese, obese (MOO). Materials and Methods: Subjects with MHNO ( n=462), MHO ( n=192), MONO ( n=315), and MOO ( n=335) were randomly selected from the Chennai Urban Rural Epidemiology Study. Adiponectin, visfatin, resistin, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), oxidized low-density lipoprotein (LDL), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay. Results: Levels of adiponectin were lowest in the MOO group, followed by the MONO, MHO, and the MHNO groups ( P=0.042), whereas the levels of visfatin ( P=0.042) and resistin ( P=0.043) were highest in the MOO group, followed by the MONO, MHO, and the MHNO groups. Levels of hs-CRP ( P=0.029), TNF-α ( P=0.036), IL-6 ( P=0.042), oxidized LDL (P=0.036), and MCP-1 ( P=0.039) increased from the MHNO to MHO to MONO to MOO phenotypes. Linear regression analysis of the parameters with body mass index (BMI) and metabolic syndrome components showed that adiponectin is negatively associated with abdominal obesity (β=−0.060; P=0.039) and BMI (β=−0.076; P=0.009) and that TNF-α is negatively associated with high-density lipoprotein levels (β=0.114, P=0.049) even after adjusting for age and gender. hs-CRP (β=0.112, P=0.020) and oxidized LDL (β=0.114, P=0.050) showed a positive association with systolic blood pressure even after adjusting for age and gender. Conclusions: The metabolically obese phenotype is characterized by altered adipokine and inflammatory profiles, which could make this phenotype at high risk for type 2 diabetes mellitus and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

AIM: The aim of the study was to assess the relationship of depression with carotid intima media thickness and augmentation index in Asian Indians. Research Design and Methods: For this study, 1505 subjects were randomly selected from a population based study conducted in Chennai, South India. Right common carotid artery intima medial thickness [IMT] was determined using high-resolution B-mode ultrasonography. Augmentation index [AI] was measured using the Sphygmocor apparatus. Depressive symptoms were assessed using a previously validated instrument, the Patient Health Questionnaire -12 (PHQ -12). Results: Of the 1505 subjects included in this study, depressive symptoms were present in 16.6% (n = 250) of the subjects. The mean IMT and AI values among subjects with depression were significantly higher than those without depression [0.83 ± 0.43 mm vs 0.73 ± 0.12 mm, P < 0.001] and IMT was higher in females with depression while AI was higher in males with depression. However, both IMT and AI were higher among those with depression in both genders. In multiple logistic regression model, depressive symptoms were associated with IMT even after adjusting for age, gender, body mass index, fasting plasma glucose, serum cholesterol and hypertension (Odds ratio [OR] =2.17, 95% Confidence intervals [CI]:1.01- 4.63, P = 0.047) but in the case of AI, the significance was lost in the adjusted model (OR = 1.01, 95% CI: 0.991-1.02, P = 0.445). Conclusion: Among Asian Indians, presence of depressive symptoms was associated with carotid intima media thickness and Augmentation index, even after adjusting for potential confounders. [ABSTRACT FROM AUTHOR]

We investigated the prevalence of peripheral vascular disease (PVD) and its association with preclinical atherosclerotic markers [intima-media thickness (IMT)] and arterial stiffness among 1755 urban south Indian type 2 diabetic subjects recruited from the Chennai Urban Rural Epidemiology Study (CURES). Doppler studies were performed, and PVD was defined as ankle–brachial index (ABI) of ≤0.9. IMT of the common carotid artery was determined using high-resolution B-mode ultrasonography, and augmentation index (AGI) was measured using the Sphygmocor apparatus. The overall prevalence of PVD was 8.3% (age-standardized 6.5%). The prevalence of PVD was higher among known diabetic subjects (n = 1401) compared to newly detected diabetic subjects (n = 354) (8.6% vs 6.8%, p = 0.250). The mean IMT and AGI in subjects with PVD were significantly higher compared to subjects without PVD (IMT: 0.99 ± 0.26 mm vs 0.83 ± 0.19 mm; AGI: 28.1 ± 9.6% vs 25.7 ± 9.8%, respectively). IMT was independently associated with PVD even after adjusting for age [odds ratio (OR) = 2.9 (1.2−6.7), p = 0.016 for second tertile and OR = 3.9 (1.7−9.3), p = 0.002 for third tertile compared to first tertile]. AGI was also associated with PVD in the unadjusted model [OR = 1.8 (1.1−3.1), p = 0.027 for second tertile compared to first tertile]. However, when adjusted for age, the significance was lost. In conclusion, among urban south Indian type 2 diabetic subjects, the prevalence of PVD is 8.3% and IMT is more strongly associated with PVD than AGI. [ABSTRACT FROM PUBLISHER]

Objective: The aim of this study was to assess the prevalence of metabolic syndrome (MS) and its association with coronary artery disease (CAD) among an elderly urban population in south India., Methods: Individuals aged ≥60 years (n=222) were recruited from Phase 3 of the Chennai Urban Rural Epidemiology Study. Anthropometric and blood pressure measurements, oral glucose tolerance test, lipids and fasting insulin were carried out. Prevalence of MS was estimated using the World Health Organization (WHO), Modified National Cholesterol Education Program's Adult Treatment Panel III (ATP-III) and International Diabetes Federation (IDF) criteria. Diagnosis of CAD was made by resting 12 lead ECG and/or past history of documented myocardial infarction., Results: MS was identified in 45.9% (n=102) by modified ATP-III, 37.4% (n=83) by IDF and 45.5% (n=101) by WHO criteria respectively. Only 61 subjects (27.5%) were identified by all the three criteria. Female subjects had a significantly higher prevalence of MS compared to their male counterparts (45.8 vs, 31.0%, p=0.023 respectively) according to IDF criteria. It was observed that 59.8%, 53% and 45.6% of the subjects had all five abnormalities according to modified ATP-III, IDF and WHO, respectively. Subjects with MS had significantly higher prevalence of CAD compared to those without MS using all the 3 criteria (modified ATP-III -20.6 vs.8.5%; IDF-20.5 vs.10.1%; WHO-19.8 vs.9.1% respectively). The odds ratio of developing CAD among MS subjects was 2.93, 2.39 and 2.48 compared to those without MS after adjusting for age, gender and family history of diabetes according to modified ATP-III, IDF and WHO, respectively., Conclusions: Nearly 40% of the elderly urban south Indians have MS and it is strongly associated with CAD.

Aim: The aim of this study was to assess levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) in South Indian subjects with and without MS and among MS subjects with and without insulin resistance (IR)., Methodology: From the population-based Chennai Urban Rural Epidemiology Study, 334 subjects with MS and 342 subjects without MS were selected. Metabolic syndrome was diagnosed based on modified National Cholesterol Education Program criteria. High-sensitivity C-reactive protein, TNF-α, IL-6, and VCAM-1 were measured by enzyme-linked immunosorbent assay. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR) using the following formula: fasting insulin (µIU/ml) × fasting glucose (mmol/liter)/22.5., Results: Subjects with MS had significantly higher levels of all four inflammatory markers compared to those without MS: hs-CRP (2.57 vs 2.19 mg/liter) (p < .05), TNF-α (4.47 vs 3.89 pg/ml) (p < .05), IL-6 (16.22 vs 10.96 pg/ml) (p < .05), and VCAM-1 (13.8 vs 7.94 pg/ml) (p < .05). In the total study subjects, hs-CRP (r = 0.089, p = .047), TNF-α (r = 0.113, p = .040), IL-6 (r = 0.176, p = .042), and VCAM-1 (r = 0.230, p = .06) were significantly correlated with MS. With increasing quartiles of IR, mean levels of hs-CRP (p for trend <.001) and TNF-α (p for trend <.05) increased linearly. MS subjects with IR had higher levels of hs-CRP (p < .001) and TNF-α (p < .05) compared to MS subjects without IR., Conclusion: In Asian Indians, inflammatory cytokines hs-CRP, TNF-α, IL-6, and VCAM-1 are elevated in subjects with MS while hs-CRP and TNF-α are further elevated in those with MS and IR., (© 2011 Diabetes Technology Society.)

Objective: To estimate the prevalence of sleep abnormalities and their association with glucose intolerance and metabolic syndrome (MS) in the normal-weight urban South Indian population., Methods: This population-based, cross-sectional study was carried out in 358 subjects aged 20-76 years randomly selected from the Chennai Urban Rural Epidemiology Study in South India. A validated questionnaire assessing various sleep abnormalities (snoring, daytime sleepiness, lack of refreshing sleep, and number of hours of sleep) was administered. All subjects underwent an oral glucose tolerance test, and anthropometric biochemical measurements were obtained to assess cardiometabolic risk factors including glucose intolerance. Diabetes risk was assessed using a previously validated Indian Diabetes Risk Score (IDRS)., Results: The overall prevalence of snoring and daytime sleepiness was 40% and 59%, respectively. Snorers were more male, older, smokers, and had higher levels of cardiometabolic risk factors. Subjects with daytime sleepiness had higher body mass index (BMI) and abdominal obesity. Both snoring (50.9% vs 30.2%, p<0.001) and daytime sleepiness (68% vs 49.7%, p<0.001) were more prevalent among subjects with impaired glucose metabolism compared to those with normal glucose metabolism. Both sleep measures were associated with higher diabetes risk scores, as assessed by the IDRS (snoring: trend χ2, 11.14, p=0.001; daytime sleepiness: trend χ2, 5.12, p=0.024). Metabolic syndrome was significantly associated with snoring even after adjusting for age, sex, family history of diabetes, physical activity, smoking, and alcohol., Conclusions: The prevalence of snoring and daytime sleepiness is high among urban South Indians and these two sleep measures are associated with glucose intolerance, MS, and higher diabetes risk scores., (© 2010 Diabetes Technology Society.)