Visceral adiposity index and 10-year cardiovascular disease incidence: The ATTICA study.

BACKGROUND AND AIMS: Visceral adiposity index (VAI) has been proposed as a marker of visceral adipose tissue accumulation/dysfunction. Our aim was to evaluate potential associations between the VAI and the 10-year cardiovascular disease (CVD) incidence. METHODS AND RESULTS: During 2001-2002, 3042 Greek adults (1514 men; age: ≥18 years) without previous CVD were recruited into the ATTICA study, whilst the 10-year study follow-up was performed in 2011-2012, recording the fatal/non-fatal CVD incidence in 2020 (1010 men) participants. The baseline VAI scores for these participants were calculated based on anthropometric and lipid variables, while VAI tertiles were extracted for further analyses. During the study follow-up a total of 317 CVD events (15.7%) were observed. At baseline, the participants' age and the prevalence of hypertension, diabetes, hypercholesterolemia and metabolic syndrome increased significantly across the VAI tertiles. After adjusting for multiple confounders, VAI exhibited a significantly independent positive association with the 10-year CVD incidence (OR = 1.05, 95%CI: 1.01, 1.10), whereas the association of the body mass index (HR = 1.03, 95%CI: 0.99, 1.08), or the waist circumference (HR = 1.01, 95%CI: 0.99, 1.02) was less prominent. Sex-specific analysis further showed that VAI remained significantly predictive of CVD in men alone (HR = 1.06, 95%CI: 1.00, 1.11) but not in women (HR = 1.06, 95%CI: 0.96, 1.10). CONCLUSIONS: Our findings show for the first time in a large-sample, long-term, prospective study in Europe that the VAI is independently associated with elevated 10-year CVD risk, particularly in men. This suggests that the VAI may be utilized as an additional indicator of long-term CVD risk for Caucasian/Mediterranean men without previous CVD.

Early ischaemic preconditioning of spinal cord enhanced the binding profile of heat shock protein 70 with neurofilaments and promoted its nuclear translocation after thoraco-abdominal aortic occlusion in pigs.

OBJECTIVE(S): Heat shock protein 70 (Hsp70) is detected in substantial amounts in normal neurons and this basal content may protect a cell against harmful conditions without the need for additional synthesis. Herein, we investigate the potential protective role of these basal levels of Hsp70, in an early ischaemic preconditioning (IPC) experimental model, suggesting a possible role of this protein as a first window of protection. DESIGN, MATERIAL AND METHODS: Forty-two pigs were used in an experimental thoraco-abdominal aortic occlusion model. Twelve animals (two groups) were used for neurological evaluation. The remaining 30 animals (five groups) were used for immunoprecipitation and immunohistochemical studies. These were performed to study the binding relationship of Hsp70/cytoskeleton elements and the cellular distribution of Hsp70, respectively. RESULTS: The IPC + ischaemia-group showed significant better neurologic scores compared with those of the ischaemia group, indicating a protective role for IPC (P = 0.003). The immunoprecipitations demonstrated that early IPC increased significantly the binding profile of Hsp70/neurofilaments (P = 0.025). In addition, translocation of Hsp70 into the nucleus was observed, which was conserved until the sustained ischaemia. CONCLUSIONS: These results indicate that Hsp70 may have an important role in early IPC of the spinal cord, by protecting neurofilaments and by ensuring the functionality and the integrity of the nucleus, at the time the intensive insult begins.

Pharmacotherapy for overweight/obesity in ethnic minorities and White Caucasians: a systematic review and meta-analysis.

Ethnic minorities in the West exhibit a higher prevalence of obesity and also under-achieve in weight management compared to White Caucasians. A systematic review of randomized controlled trials (RCTs) in adults (mean age ≥18 years, duration ≥6 months and published in the English language) was undertaken to evaluate the effectiveness of antiobesity drugs in ethnic minorities and White Caucasians. Data sources between 1990 and 2010 were searched including MEDLINE, EMBASE, Cochrane Controlled Trials Register, CINAHL and references cited in the included studies of other reviews. Eighteen RCTs that met the inclusion criteria were included in this review (6 sibutramine and 12 orlistat). A random effects model was used for meta-analysis. An indirect comparison of weight loss in sibutramine-treated patients in ethnic minorities was significantly lower than in White Caucasians: -2.7 kg (95% CI: -3.1 to -2.3) versus -4.4 kg (95% CI: -5.0 to -3.8), respectively. For orlistat, weight loss was similar in the two groups: -2.3 kg (95% CI: -2.6 to -2.0) in ethnic minorities and -2.8 kg (95% CI: -5.1 to -0.5) in White Caucasian participants. Overall, there were few studies of weight loss pharmacotherapy for comparison of this review and it was not possible to analyse data based on ethnic groupings. More ethnically tailored studies are needed to assess the most effective weight loss strategies in these most metabolically vulnerable groups.

Audit of vaccination status of health-care workers who tested positive for SARS-CoV-2.

Multiple SARS-CoV-2 vaccinations have shown excellent efficacy during clinical trials. However, post vaccine surveillance is important to confirm 'real-world' findings of vaccine efficacy and safety. It is therefore imperative to identify individuals that become infected with SARS-CoV-2 post vaccination. We investigated the vaccination status of staff that had tested positive in a cohort of healthcare workers in one large tertiary hospital in the UK. At the time of the investigation, 8th December 2020 to 13th March 2021, 11,871 staff had been vaccinated and 225 staff tested positive for SARS-CoV-2. This period coincided with the second wave of SARS-CoV-2 infections in the UK which was driven by the Alpha variant. No healthcare workers who were double vaccinated had a positive PCR test for SARS-CoV-2 during this study period confirming vaccination with Pfizer BioNTec BNT162b2 gives excellent protection against infection of this variant.

Healthcare staff perceptions and misconceptions regarding antibody testing in the United Kingdom: implications for the next steps for antibody screening.

BACKGROUND: Healthcare workers have been at increased risk of exposure, infection and serious complications from COVID-19. Antibody testing has been used to identify staff members who have been previously infected by SARS-CoV-2, and has been rolled out rapidly in the United Kingdom. A number of comment and editorial articles have been published that raise concerns about antibody testing in this context. We present perceptions of National Health Service (NHS) healthcare workers in relation to SARS-CoV-2 antibody testing. METHODS: An electronic survey regarding perceptions towards SARS-CoV-2 antibody testing was distributed to all healthcare workers at a major NHS tertiary hospital following implementation of antibody testing. RESULTS: In total, 560 healthcare workers completed the survey (80% female; 25% of Black and Minority Ethnic background; 58% from frontline clinical staff). Exploring whether they previously had COVID-19 was the primary reported reason for choosing to undergo antibody testing (85.2%). In case of a positive antibody test, 72% reported that they would feel relieved, whilst 48% felt that they would be happier to work in a patient-facing area. Moreover, 12% responded that a positive test would mean "social distancing is less important", with 34% of the responders indicating that in this case they would be both less likely to catch COVID-19 and happier to visit friends/relatives. CONCLUSIONS: NHS staff members primarily seek out SARS-CoV-2 antibody testing for an appropriate reason. Based on our findings and given the lack of definite data regarding the extent of immunity protection from a positive SARS-CoV-2 antibody test, significant concerns may be raised regarding the reported interpretation by healthcare workers of positive antibody test results. This needs to be further explored and addressed to protect NHS staff and patients.

Dose-dependent effects of recombinant human interleukin-6 on glucose regulation.

Inflammatory cytokines have metabolic actions that probably contribute to the general adaptation of the organism during infectious or inflammatory stress. To examine the effects of interleukin 6 (IL-6), the main circulating cytokine, on glucose metabolism in man, we performed dose-response studies of recombinant human IL-6 in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/Kg BW) were injected sc in 15 healthy male volunteers (3 in each dose) after a 12-h fast. All IL-6 doses were tolerated well and produced no significant adverse effects. We measured the circulating levels of glucose, insulin, C-peptide, and glucagon at baseline and half-hourly over 4 h after the IL-6 injection. Mean peak plasma levels of IL-6 were achieved between 120 and 240 min and were 8, 22, 65, 290, and 4050 pg/mL, respectively, for the 5 doses. After administration of the 2 smaller IL-6 doses, we observed no significant changes in plasma glucose levels, which, because of continued fasting, decreased slightly over time. By 60 min after the 3 higher IL-6 doses, however, the decline in fasting blood glucose was arrested, and glucose levels increased in a dose-dependent fashion. The concurrent levels of plasma insulin and C-peptide were not affected by any IL-6 dose. In contrast, IL-6 caused significant increases in plasma glucagon levels, which peaked between 120 and 150 min after the IL-6 injection. In conclusion, sc IL-6 administration induced dose-dependent increases in fasting blood glucose, probably by stimulating glucagon release and other counteregulatory hormones and/or by inducing peripheral resistance to insulin action.

Dose-dependent effects of recombinant human interleukin-6 on the pituitary-testicular axis.

Inflammatory cytokines are soluble mediators of immune function that also regulate intermediate metabolism and several endocrine axes. To examine the effects of interleukin-6 (IL-6), the main circulating cytokine, on the hypothalamic-pituitary-testicular axis in men, we performed dose-response studies of recombinant human IL-6 (rHuIL-6) in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 microg/kg body weight) were injected subcutaneously into 15 healthy male volunteers (3 at each dose) in the morning. We measured the circulating levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone binding globulin (SHBG) at baseline and then at 24 h, 48 h, and 7 days after the IL-6 injection. LH and FSH levels were also measured half-hourly for the first 4 h after the IL-6 injection. All IL-6 doses were tolerated well and produced no significant adverse effects. Mean peak plasma IL-6 levels achieved after IL-6 administration were 8 +/- 1, 22 +/- 5, 65 +/- 22, 290 +/- 38, and 4050 +/- 149 pg/ml, respectively for the five doses. We observed no significant changes in plasma testosterone levels after the two smaller IL-6 doses. The three higher IL-6 doses, however, caused significant decreases in testosterone levels by 24 h, which persisted at 48 h and returned to baseline by 7 days. The higher testosterone suppression was after the 3.0 microg/kg dose, making the dose-response curve bell-shaped. There also appeared to be small but not significant increases in LH levels after the three higher IL-6 doses, which were not acute and seemed to follow temporally the testosterone decreases. The concurrent plasma levels of FSH and SHBG were not appreciably affected by any IL-6 dose. In conclusion, subcutaneous IL-6 administration, which caused acute elevations in circulating IL-6 levels of a similar magnitude to those observed in severe inflammatory and noninflammatory stress, induced prolonged suppression in testosterone levels in healthy men without apparent changes in gonadotropin levels. This suggests that IL-6 might induce persistent testicular resistance to LH action or suppression of Leydig cell steroidogenesis or both, with potential adverse effects on male reproductive function.

Circulating tumor necrosis factor alpha concentrations are higher in abdominal versus peripheral obesity.

Fat tissue is a significant source of endogenous tumor necrosis factor alpha (TNFalpha), the pluripotent cytokine that plays an important role as a mediator of the peripheral insulin resistance found in obesity. The majority of evidence for this role of TNFalpha is from studies in animal models of obesity. To explore further the role of TNFalpha in the pathogenesis of obesity-related insulin resistance in humans, we compared plasma levels of TNFalpha and the other main endocrine cytokine, interleukin-6 ([IL-6] both measured by enzyme-linked immunosorbent assay), in 26 obese women (body mass index [BMI] > 30 kg/m2) and 13 female controls (BMI < 26 kg/m2) without a history of recent or active infection. Glucose and insulin levels were measured at 0, 1, and 2 hours after a 75-g oral glucose load. There was no significant difference in plasma TNFalpha or IL-6 levels between obese and non-obese subjects overall (2.10 +/- 0.19 v 1.65 +/- 0.18 pg/mL and 2.06 +/- 0.29 v 1.50 +/- 0.17 pg/mL, respectively). However, TNFalpha levels were significantly elevated in obese subjects with a 2-hour glucose level more than 140 mg/dL (n = 8) compared with the other obese subjects (n = 18) and the non-obese controls (2.88 +/- 0.46 v 1.75 +/- 0.10 and 1.65 +/- 0.18 pg/mL, respectively, P < .01). Furthermore, the TNFalpha level correlated significantly with the waist to hip ratio ([WHR] r = .53, P < .01) and fasting and post-oral glucose tolerance test (OGTT) insulin levels (r = .47, P < .02), but not with the BMI, and was higher in obese women with a WHR more than 0.90 (n = 14) in comparison to those with a WHR less than 0.90 (n = 12, 2.47 +/- 0.29 v 1.66 +/- 0.18 pg/mL, respectively, P < .03). The corresponding plasma leptin level was significantly higher in obese women versus the control group (41.6 +/- 2.5 v22.3 +/- 2.9 ng/mL, P < .001) and was related to the BMI (r = .60, P < .01) but not to TNFalpha or the WHR. There were no significant differences in the corresponding IL-6 concentration between groups, and IL-6 did not correlate with TNFalpha, leptin, BMI, WHR, or insulin levels. In conclusion, circulating TNFalpha levels are higher in abdominal obesity compared with peripheral obesity, and may contribute to the insulin resistance that more commonly complicates the former pattern of fat distribution.

Experimental echinococcus infection in the mouse model: pericystic cellular immunity reaction and effects on the lymphoid organs of immunocompetent and thymectomized mice.

Echinococcus can infect man as an accidental intermediate host causing hydatid disease. The infection persists and the growth of the cysts advances, while the patient usually remains asymptomatic for years. Experimental Echinococcus infection in mice provides a well described model for the study of the parasite-host relationship that permits the evolution of the disease despite the activation of the host's immune system. The aim of the present study was to assess the immune response to Echinococcus infection in normal and thymectomized mice. For this purpose, a total of 150 mice, divided into three equal groups (A, B and C), were infected by intraperitoneal inoculation of live protoscoleses. The mice of groups B and C underwent thymectomy, two weeks prior and after the infection, respectively. The mice of each group were further divided into three subgroups and were sacrificed at three consecutive time points: 45 days, 3 and 6 months post the infection. The hydatid cysts that subsequently developed by the metacestode-lavral stage, along with the spleen and lymph nodes were excised from each mouse and histologically studied. The results revealed a marked activation of the cell-mediated immunity against the parasite at the early stages of the disease. The initial response of the host abated with time and was minimal six months after the infection suggesting a local immunosuppression state that could account for the advancement of the disease. In addition, the thymectomized mice exhibited a higher susceptibility to the infection, which corresponded to the weak and delayed cellular immunity response observed in these groups. These results suggest that the cell-mediated immunity is crucial for the defense against Echinococcus, especially early in the course of the disease where suppression of larval growth is critical for the final outcome of the infection.

Insights into 'fermentonomics': evaluation of volatile organic compounds (VOCs) in human disease using an electronic 'e-nose'.

Detection of volatile organic compounds (VOCs) is a common requirement in industry for which numerous methods are available. The electronic nose (e-nose) is an example. Rather than individual chemicals, the e-nose recognizes the 'aroma fingerprint' created by the collection of VOCs in samples, comparable to the human nose. We report on a novel application for gastrointestinal and metabolic medicine, and compare its results to mass spectrometry. Fermentation of undigested foods in the large bowel by its resident bacteria results in the creation of several chemicals including volatile gases that influence colonic and metabolic health. Using urine samples, preliminary results indicate the ability of the e-nose to distinguish between controls and those with inflammatory bowel disease or diabetes (separation rate of ∼97%). This emphasizes the different patterns of fermentation. Our term 'fermentonomics' describes the investigation and analysis of the fermentome by such non-invasive means. Such an approach has potentially wide application in medicine.

Self-reported disability in adults with severe obesity.

Self-reported disability in performing daily life activities was assessed in adults with severe obesity (BMI ≥ 35 kg/m(2)) using the Health Assessment Questionnaire (HAQ). 262 participants were recruited into three BMI groups: Group I: 35-39.99 kg/m(2); Group II: 40-44.99 kg/m(2); Group III: ≥45.0 kg/m(2). Progressively increasing HAQ scores were documented with higher BMI; Group I HAQ score: 0.125 (median) (range: 0-1.75); Group II HAQ score: 0.375 (0-2.5); Group III HAQ score: 0.75 (0-2.65) (Group III versus II P < 0.001; Group III versus I P < 0.001; Group II versus I P = 0.004). HAQ score strongly correlated with BMI and age. Nearly three-fourths of the study participants reported some degree of disability (HAQ score > 0). The prevalence of this degree of disability increased with increasing BMI and age. It also correlated to type 2 diabetes, metabolic syndrome, and clinical depression, but not to gender. Our data suggest that severe obesity is associated with self-reported disability in performing common daily life activities, with increasing degree of disability as BMI increases over 35 kg/m(2). Functional assessment is crucial in obesity management, and establishing the disability profiles of obese patients is integral to both meet the specific healthcare needs of individuals and develop evidence-based public health programs, interventions, and priorities.

Self-Reported Psychosocial Health in Obese Patients before and after Weight Loss.

Psychosocial profiles were examined in 255 morbidly obese patients attending a hospital service offering access to standard weight loss therapies. 129 patients were reassessed after at least 6-month follow-up. At baseline, 51.8% and 32.7% of patients, respectively, had evidence of anxiety and depressive disorders, 24% had severe impairments in self esteem, and 29.7% had an increased risk of eating disorders. At follow-up, weight loss from baseline was significant in all 3 therapies: diet only is 0.74 +/- 1.8 kg; pharmacotherapy is 6.7 +/- 4.2 kg; and surgery is 20.1 +/- 13.6 kg. Anxiety scores improved in all three groups (P < .05). Patients having pharmacotherapy or surgery had significant improvements in physical and work function and public distress compared to those having dietary treatment only (P < .05). Our observational data suggest that weight management services can lead to psychosocial benefit in morbidly obese patients. Well-designed studies are necessary to examine the link between weight loss and emotional health.

Dietary and lifestyle interventions for weight management in adults from minority ethnic/non-White groups: a systematic review.

Minority ethnic/non-White populations are more prone to weight gain and more susceptible to obesity-related complications. The objective of this study was to systematically review dietary and lifestyle interventions for weight management in minority ethnic groups. Electronic databases and reference lists of original studies and reviews were searched for studies on dietary and lifestyle weight management interventions published. Randomized clinical trials with ≥6-month duration were included. Nineteen studies met the inclusion criteria. Fourteen studies involved African-Americans, one in non-White Hispanics, one in Japanese Americans and three in both African-Americans and non-White Hispanics. Most of the interventions proved relatively effective. However, significant drawbacks were noted for several of these studies, such as small sample size, high attrition rates and lack of follow-up data. Better quality and long-term trials are required in order to investigate in detail the effectiveness of lifestyle changes for weight management in these populations and eventually support evidence-based recommendations.

Stress mechanisms and metabolic complications.

Stress can be defined as a state of threatened homeostasis or disharmony. An intricate repertoire of physiologic and behavioral responses is mobilized under stressful situations forming the adaptive stress response that aims to reestablish the challenged body equilibrium. The hypothalamic-pituitary-adrenal axis and the central and peripheral components of the autonomic nervous system constitute the two main pillars that subserve the vital functions of the stress system. Chronic stress represents a prolonged threat to homeostasis that can progressively lead to a deleterious overload with various complications caused by both the persistent stressor and the detrimental prolongation of the adaptive response. Recent data indicate that chronic stress is associated to derangement of metabolic homeostasis that contributes to the clinical presentation of visceral obesity, type 2 diabetes, atherosclerosis and metabolic syndrome. Notably, indices of stress in the modern western societies correlate with the increasing incidence of both obesity and the metabolic syndrome which have reached epidemic proportions over the past decades. The pathogenetic mechanisms that accommodate these correlations implicate primarily the chronic hyperactivation of the HPA axis under prolonged stress, which favors accumulation of visceral fat, and VICE VERSA; obesity constitutes a chronic stressful state that may cause HPA axis dysfunction. In addition, obesity is being now recognized as a systemic low grade inflammatory state that contributes to the derangement of the metabolic equilibrium, implicating the adipocyte secretion of adipokines to the pathogenesis of several components of the metabolic syndrome. Understanding the mechanisms that mediate the documented reciprocal relationships between stress and metabolic homeostasis will hopefully provide novel insights to the pathophysiology of obesity, type 2 diabetes, and their cardiometabolic complications, and will help the quest for more specific and effective therapeutic interventions.

Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure.

Interleukin-6 (IL-6), the main circulating cytokine, is putatively a major mediator of the effects of the immune system on several endocrine axes and intermediate metabolism. We performed dose-response studies of recombinant human IL-6 on pituitary hormone secretion in 15 healthy male volunteers, using 5 single, escalating subcutaneous doses of IL-6 (0.1, 0.3, 1.0, 3.0 and 10.0 micrograms/kg body weight), each in 3 volunteers. We measured resting metabolic rate (RMR) with indirect calorimetry and plasma anterior pituitary hormones and vasopressin (AVP) at baseline and half-hourly over 4 h after the injection. All doses examined were tolerated well and produced no significant adverse effects. Dose-dependent RMR increases were observed in response to the 3.0- and 10.0-microgram/kg doses of IL-6, beginning at 60 min and slowly peaking between 180 and 240 min. Plasma adrenocorticotropic-hormone concentrations increased dramatically and dose-dependently in all the patients who received the 3.0- and 10.0-microgram/kg doses of IL-6, respectively, peaking to 150 and 255 pg/ml at 60 min, and slowly returning to normal by 4 h. Corresponding plasma cortisol levels peaked dose-dependently between 90 and 150 min, but remained elevated throughout the sampling period. In contrast, the growth hormone (GH) dose-response was bell-shaped, with maximum (approximately 100-fold) stimulation achieved by 3.0 micrograms/kg IL-6. Prolactin (PRL) showed a similar but less pronounced response pattern. Thyroid-stimulating hormone (TSH) dose-dependently and progressively decreased over the 240 min, while gonadotropins showed no clear-cut changes. In conclusion, subcutaneous IL-6 administration induced synchronized dose-dependent increases in the RMR and hypothalamic-pituitary-adrenal axis activity, suggesting that hypothalamic corticotropin-releasing hormone may mediate both of these functions in humans. IL-6 also acutely stimulated GH and PRL secretion and suppressed TSH secretion. The dose of 3.0 micrograms/kg could be used safely in the study of patients with disturbances of the hypothalamic-pituitary unit or of thermogenesis.