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Background and Objectives: Only 10% of Americans with substance use disorders (SUDs) receive treatment with insufficient treatment access and screening practices proposed and potential contributing factors., Methods: This retrospective cross-sectional study used National Survey on Drug Use and Health (NSDUH) data to assess individuals with SUDs receiving treatment between 2016 and 2019 (survey n = 12,111; weighted n = 12,394,214). Demographic, access, and screening characteristics were investigated as predictors of treatment receipt using time-series logistic regression analyses to test trends and assessed treatment receipt odds, controlling for demographic and treatment characteristics., Results: For those with past-year SUDs, 13.0% reported receiving past-year SUD treatment (survey n = 1605; weighted n = 1,612,154). The SUD treatment receipt rate remained statistically stable from 2016 to 2019, with a nonsignificant treatment receipt trend declining from 14% to 12%. Treatment changes were notable among Native Americans (+53.80%), Pacific Islanders (+94.10%), multiracial (-59.96%), ages 65+ (-70.18%), and ages 12-17 (-50.70%). In the regression model, race, sex, age, insurance status, and receiving mental health treatment were associated with SUD treatment receipt., Discussion and Conclusions: The treatment gap remains substantial and stable. Annually, about 87% of Americans with SUDs are not receiving the treatment they need. Asian Americans were less likely and those attending general mental health services were more likely to receive treatment., Scientific Significance: We present an updated SUD treatment gap evaluation, and identify access and screening characteristics associated with SUD treatment receipt. Policymakers, clinicians, and researchers must continue improving access and identification of those in need of care., (© 2023 The American Academy of Addiction Psychiatry (AAAP).)

This scoping review aims to identify interventional training courses on tobacco cessation counseling skills of medical students, identify the most appropriate teaching method, and the ideal stage to provide such training. We retrieved articles published since 2000 from two electronic peer-reviewed databases (PubMed and Scopus) and hand-searched reference lists of selected articles. Articles published in English, with a clearly defined curriculum, reporting knowledge, attitude, cessation counseling skills of medical students post-training, and cessation-related outcomes of patients participating in student-led counseling sessions, were considered for inclusion. We used the York framework to guide this scoping review. First, data from studies meeting the inclusion criteria were charted using a standardized form. Subsequently, related studies were organized under three themes that emerged in the review process-lectured-based, web-based, and multi-modal curriculum. We concluded that a short but focused lecture-based curriculum combined with peer role-play or standardized/real patient interactions effectively develops the necessary knowledge and skills of undergraduate medical students to provide tobacco cessation counseling to patients. However, studies consistently report that the gains in knowledge and skills after cessation training is acute. Therefore, continued participation in cessation counseling and periodic review of cessation-related knowledge and skills post-training is warranted., (© 2023. The Author(s) under exclusive licence to American Association for Cancer Education.)

Globally, Japan has the lowest rate of vaccine confidence. The persistent parental vaccine hesitancy has been attributed to safety and efficacy concerns and is primarily driven by the negative experience with human papillomavirus (HPV) vaccines. This literature review aimed to identify factors associated with HPV vaccine uptake and potential strategies to reduce vaccine hesitancy among Japanese parents. Articles published in English or Japanese between January 1998 and October 2022 that examined Japanese parental factors for HPV vaccine uptake were identified from PubMed, Web of Science, and Ichushi-Web. In total, 17 articles met the inclusion criteria. Four key themes which affected HPV vaccine hesitancy and acceptance were identified: perceptions of risk and benefits, trust and recommendation, information and knowledge, and sociodemographic characteristics. While governmental and healthcare provider recommendations are important factors, efforts to improve parental confidence in the HPV vaccine are required. Future interventions to counteract HPV vaccine hesitancy should actively disseminate information on vaccine safety and effectiveness, along with information on the severity and susceptibility of HPV infection., Competing Interests: The authors declare no conflict of interest.

Background: Black clients in substance use disorder (SUD) treatment are associated with the lowest successful completion and substance use reductions. More work is needed to identify specific factors that support successful recovery of Black clients., Methods: Data from U.S. outpatient SUD treatment facilities receiving public funding from 2015 to 2019 were analyzed (N = 2239,197). Primary analyses consisted of Black clients (n = 277,726) reporting admission and discharge substance use frequency. Multiple logistic regression was used to predict substance use frequency improvement from Black client demographic, recovery capital, treatment characteristics, and state. Disparities were compared between Black and non-Black clients., Results: The overall Black client improvement percentage was 46.95%. Mutual-help group attendance and Length of Stay demonstrated clinically meaningful effect sizes controlling for all other variables and state. Attending mutual-help groups 8-30 times per month (State aOR = 2.54, 95% CI = 2.43, 2.64) and outpatient treatment stays of 4 months or more (State aOR = 2.50, 95% CI = 2.44, 2.56) were factors supporting Black client improvement. Importantly, states are associated with disparate Black client risk differences and only South Dakota had greater Black improvement (RD = 6.35, 95% CI = 1.00, 11.71)., Conclusions: Black client factors supporting substance use improvement include ancillary mutual-help group attendance and increased treatment retention. These factors may be more critical in states with larger Black improvement disparities. In general, treatment providers increasing access to mutual-help groups, and adjusting program inclusiveness and motivational factors for retention, would make strides in increasing improvement outcomes for Black clients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Health Japan 21 is Japan's premier health promotion policy encompassing preventive community health measures for lifestyle-related diseases. In this repeated cross-sectional survey, we report 24-year trends of type 2 diabetes mellitus (T2DM), obesity, hypertension, and their association with dietary intakes to evaluate Health Japan 21's impact and identify gaps for future policy implementation. We analyzed data from 217,519 and 232,821 adults participating in the physical examination and dietary intake assessment, respectively, of the National Health and Nutrition Survey 1995-2019. Average HbA1c and BMI have significantly increased along with the prevalence of T2DM and overweight/obesity among males. Despite a significant decrease in daily salt intake, the decline in the combined prevalence of Grades 1-3 hypertension was non-significant. Seafood and meat intakes showed strong opposing trends during the study period, indicating a dietary shift in the Japanese population. Neither salt nor vegetable/fruit intake reached the target set by Health Japan 21. Metabolic disease trend differences between males and females highlight the need for a gender-specific health promotion policy. Future Health Japan 21 implementation must also consider locally emerging dietary trends.

Background: Since the association between disparity in physician distribution and specific healthcare outcomes is poorly documented, we aimed to clarify the association between physician maldistribution and cerebrovascular disease (CeVD), a high-priority health outcome in Japan., Methods: In this cross-sectional study, we conducted multivariable regression analysis with the Physician Uneven Distribution Index (PUDI), a recently developed and adopted policy index in Japan that uniquely incorporates the gap between medical supply and demand, as the independent variable and CeVD death rate as the dependent variable. Population density, mean annual income, and prevalence of hypertension were used as covariates., Results: The coefficient of the PUDI for the CeVD death rate was -0.34 (95%CI: -0.49--0.19) before adjusting for covariates and was -0.19 (95%CI: -0.30--0.07) after adjusting. The adjusted R squared of the analysis for the PUDI was 0.71 in the final model. However, the same multivariable regression model showed that the number of physicians per 100,000 people (NPPP) was not associated with the CeVD death rates before or after adjusting for the covariates., Conclusion: Incorporating the gap between the medical supply and demand in physician maldistribution indices could improve the responsiveness of the index for assessing the disparity in healthcare outcomes.

Background: Fishing communities in many Sub-Saharan African countries are a high-risk population group disproportionately affected by the HIV epidemic. In Uganda, literature on HIV in fishing communities has grown extensively since the first country's documented case of HIV in a fishing community in 1985. The current study describes the status of the HIV burden, prevention, and treatment in Ugandan fishing communities., Method: This scoping review was conducted based on the York Framework outlined by Arksey and O'Malley. We searched the PubMed, Embase, and Web of Science databases to identify relevant quantitative and qualitative studies on HIV incidence, HIV prevalence, HIV-related risk factors, HIV testing, antiretroviral therapy coverage and adherence, and interventions to improve treatment outcomes and reduce HIV risk factors., Results & Conclusion: We identified 52 papers and 2 reports. Thirty-four were quantitative, 17 qualitative, and 3 had a mixed-methods design. Eleven studies reported on the prevalence of HIV and 8 on HIV incidence; 9 studies documented factors associated with HIV incidence or HIV positive status; 10 studies reported on HIV testing coverage and/or associated factors; 7 reported on antiretroviral therapy coverage/adherence/outcomes; and 1 study reported on the impact of combination HIV interventions in fishing communities. This scoping review revealed a significant lack of evidence in terms of what works in HIV prevention and for improving adherence to ART, in contrast to the relatively large amount of evidence from observational quantitative and qualitative studies on HIV prevalence, incidence and related risk factors in Ugandan fishing communities. Intervention studies are urgently needed to fill the current evidence gaps in HIV prevention and ART adherence., Competing Interests: The authors have declared that no competing interests exist.

Numerous socio-legal factors make the process of surrogate decision-making for people living in dementia very complicated in Japan. In this discussion paper, we argue that the lack of early consultation between patients, surrogate decision-makers and healthcare providers and the overreliance of patients and their families on doctors to assume the decision-making role lead to healthcare practices that may not align with the patient's wishes. Further, we argue that lack of laws on surrogate decision-making, changing family structure and the liabilities associated with the care of people living with dementia contribute to the complexity of the decision-making process in Japan. Finally, given the rapidly changing social and healthcare norms in Japan, we call for greater involvement of nurses and care workers in the decision-making process to ensure patient-centric treatment and care are adopted., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Japan is a high tobacco burden country with over 20 million smokers in 2017. Tobacco control measures in Japan has been criticised as largely inadequate and ineffective despite ratifying the World Health Organization's Framework Convention on Tobacco Control in 2004. Numerous factors such as pro-tobacco legislators, regulatory oversight of the primary Japanese tobacco company from the Ministry of Finance and industry interference on the policy-making process in Japan have prevented aggressive tobacco control efforts. Given the intricate challenges in Japan, it is important to develop feasible and effective smoking cessation strategies. In this paper, we have analysed the trends in tobacco prices, sale and smoking prevalence, major tobacco/smoking policies and some of the industry-related challenges that have prevented the development of effective tobacco control measures in Japan. We have emphasised the need for stronger implementation of the World Health Organization's Framework Convention on Tobacco Control and its MPOWER policy package and to separate the tobacco industry from the tobacco control policymaking process to promote cessation and abstinence from smoking and better sensitisation against exposure to second-hand smoke., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Gastric inhibitory polypeptide (GIP) is an incretin secreted from enteroendocrine K cells and potentiates insulin secretion from pancreatic β-cells. GIP also enhances long-chain triglyceride (LCT) diet-induced obesity and insulin resistance. Long-term intake of medium-chain triglyceride (MCT) diet is known to induce less body weight and fat mass gain than that of LCT diet. However, the effect of MCT diet feeding on GIP secretion and the effect of GIP on body weight and fat mass under MCT diet-feeding condition are unknown. In this study, we evaluated the effect of single MCT oil administration on GIP secretion and compared the effect of long-term MCT and LCT diet on body weight and fat mass gain in wild-type (WT) and GIP-knockout (GIP KO) mice. Single administration of LCT oil induced GIP secretion but that of MCT oil did not in WT mice. Long-term intake of LCT diet induced GIP hypersecretion and significant body weight and fat mass gain compared with that of control fat (CF) diet in WT mice. In contrast, MCT diet did not induce GIP hypersecretion, and MCT diet-fed mice showed smaller increase in body weight and fat mass gain compared with CF diet-fed mice. In GIP KO mice, body weight and fat mass were markedly attenuated in LCT diet-fed mice but not in MCT diet-fed mice. Our results suggest that long-term intake of MCT diet stimulates less GIP secretion and suppresses body weight and fat mass gain compared with that of LCT diet.

Metabolic syndrome (MetS) represents a group of abnormalities that enhances the risk for cardiovascular disease, diabetes and stroke. The Mediterranean diet seems to be an important dietary pattern, which reduces the incidence of MetS. Hydroxytyrosol (HT) - a simple phenol found in olive oil - has received increased attention for its antioxidant activity. Recently, the European Foods Safety Authority (EFSA) claimed that dietary consumption of HT exhibits a protective role against cardiovascular disease. In this study, an experimental protocol has been setup, including isolated HT administration in a diet induced model of MetS in young Wistar rats, in order to find out whether HT has a protective effect against MetS. Rats were randomly divided into two groups nurtured by high-carbohydrate high-fat (H) (MetS inducing diet) and high-carbohydrate high-fat + HT (HHT). HT (20mg/kg/d oral gavage, water vehicle) was administered for 8 weeks on the basal diet. Previous pharmacological evaluation of HT showed that hepatic steatosis was reduced and the inflammatory cells into the liver were infiltrated. These indicate that HT shows bioactivity against metabolic syndrome. Therefore, the metabolomics evaluation of liver extracts would indicate the putative biochemical mechanisms of HT activity. Thus, the extracts of liver tissues were analyzed using Ultra Performance Liquid Chromatography - High Resolution Mass Spectrometry (UPLC-HRMS, Orbitrap Discovery) and Nuclear Magnetic Resonance (NMR) spectroscopy (Bruker Avance III 600MHz). Multivariate analysis was performed in order to gain insight on the metabolic effects of HT administration on the liver metabolome. Normalization employing multiple internal standards and Quality Control-based Robust LOESS (LOcally Estimated Scatterplot Smoothing) Signal Correction algorithm (QC-RLSC) was added in the processing pipeline to enhance the reliability of metabolomic analysis by reducing unwanted information. Experimentally, HHT rats were clearly distinguished from H in PLS-DA, showing differences in the liver metabolome between the groups and specific biomarkers were determined supporting the pharmacological findings. More specifically, HT has shown to be effective towards the mobilization of lipids as various lipid classes being differentially regulated between the H and HHT groups. Interestingly branched fatty acid esters of hydroxy oleic acids (OAHSA) lipids have been shown to be up regulated to the HHT group, denoting the alleviation of the MetS to the animals administered with HT., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Metabolic syndrome is a clustering of interrelated risk factors for cardiovascular disease and diabetes. The Mediterranean diet has been proposed as an important dietary pattern to confer cardioprotection by attenuating risk factors of metabolic syndrome. Hydroxytyrosol (HT) is present in olive fruit and oil, which are basic constituents of the Mediterranean diet. In this study, we have shown that treatment with HT (20mg/kg/d for 8 weeks) decreased adiposity, improved impaired glucose and insulin tolerance, improved endothelial function with lower systolic blood pressure, decreased left ventricular fibrosis and resultant diastolic stiffness and reduced markers of liver damage in a diet-induced rat model of metabolic syndrome. These results were accompanied by reduced infiltration of monocytes/macrophages into the heart with reduced biomarkers of oxidative stress. Furthermore, in an HRMS-based metabolism study of HT, we have identified 24 HT phase I and II metabolites, six of them being over-produced in high-starch, low-fat diet fed rats treated with HT compared to obese rats on high-carbohydrate, high-fat diet. These results provide direct evidence for cardioprotective effects of hydroxytyrosol by attenuation of metabolic risk factors. The implications of altered metabolism of HT in high-carbohydrate, high-fat diet fed obese rats warrant further investigation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Hydroxytyrosol (HT), an important component of olive fruit and olive oil, improves the signs of metabolic syndrome in rats following chronic treatment. At a dose of 20mg/kg/day, HT decreased adiposity and improved cardiovascular and liver structure and function in rats fed with a high-carbohydrate, high-fat diet. An untargeted metabolomics approach has been employed using both UPLC-Orbitrap and -QqTOF methods to identify the changes induced by chronic HT administration on the plasma metabolome. 31 metabolites have been found to be differentially expressed between the examined groups. HT was shown to decrease biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, and the metabolism of linoleic acid, retinol, sphingolipids and arachidonic acid, whereas glycerolipid metabolism is up-regulated. These are plausible mechanisms for the attenuation by HT of cardiovascular, liver and metabolic changes in high-carbohydrate, high-fat diet fed rats., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom.

Obesity and dyslipidaemia are metabolic defects resulting from impaired lipid metabolism. These impairments are associated with the development of cardiovascular disease and non-alcoholic fatty liver disease. Correcting the defects in lipid metabolism may attenuate obesity and dyslipidaemia, and reduce cardiovascular risk and liver damage. L-Carnitine supplementation was used in this study to enhance fatty acid oxidation so as to ameliorate diet-induced disturbances in lipid metabolism. Male Wistar rats (8-9 weeks old) were fed with either corn starch or high-carbohydrate, high-fat diets for 16 weeks. Separate groups were supplemented with L-carnitine (1.2% in food) on either diet for the last 8 weeks of the protocol. High-carbohydrate, high-fat diet-fed rats showed central obesity, dyslipidaemia, hypertension, impaired glucose tolerance, hyperinsulinaemia, cardiovascular remodelling and non-alcoholic fatty liver disease. L-Carnitine supplementation attenuated these high-carbohydrate, high-fat diet-induced changes, together with modifications in lipid metabolism including the inhibition of stearoyl-CoA desaturase-1 activity, reduced storage of short-chain monounsaturated fatty acids in the tissues with decreased linoleic acid content and trans fatty acids stored in retroperitoneal fat. Thus, L-carnitine supplementation attenuated the signs of metabolic syndrome through inhibition of stearoyl-CoA desaturase-1 activity, preferential β-oxidation of some fatty acids and increased storage of saturated fatty acids and relatively inert oleic acid in the tissues.

Westernised dietary patterns are characterised by an increased intake of saturated (SFA) and trans fat (TFA) and a high n-6:n-3 polyunsaturated fatty acid (PUFA) ratio. These changes together with increased sugar intake have been implicated in the progression and development of metabolic syndrome. It is now recognised that the type of dietary fat plays a far more significant role in well-being than the absolute amount. This has led to the generalisations that TFA and SFA are detrimental, MUFA is neutral and PUFA is cardioprotective. However, different dietary fatty acids even within the same chemical class elicit different physiological responses. Thus, generalising fatty acids by the degree of unsaturation or the configuration of double bonds alone is unlikely to predict biological responses. In this review, we have examined the effects of different dietary fatty acids on the cardiometabolic risk factors and propose a revised classification based on current evidence of biological activity, rather than chemical structure. Specifically, we propose that dietary fatty acids be classified into five classes as neutral, reduce one or more cardiometabolic risk factors, increase one or more cardiometabolic risk factor, controversial evidence to allow classification and inadequate research to allow classification as a basis for further discussions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The widespread acceptance that increased dietary n-3 polyunsaturated fatty acids (PUFAs), especially α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), improve health is based on extensive studies in animals, isolated cells and humans. Visceral adiposity is part of the metabolic syndrome, together with insulin resistance, dyslipidemia, hypertension and inflammation. Alleviation of metabolic syndrome requires normalization of insulin release and responses. This review assesses our current knowledge of the mechanisms that allow n-3 PUFAs to improve insulin secretion and sensitivity. EPA has been more extensively studied than either ALA or DHA. The complex actions of EPA include increased G-protein-receptor-mediated release of glucagon-like peptide 1 (GLP-1) from enteroendocrine L-cells in the intestine, up-regulation of the apelin pathway and down-regulation of other control pathways to promote insulin secretion by the pancreatic β-cells, together with suppression of inflammatory responses to adipokines, inhibition of peroxisome proliferator-activated receptor α actions and prevention of decreased insulin-like growth factor-1 secretion to improve peripheral insulin responses. The receptors involved and the mechanisms of action probably differ for ALA and DHA, with antiobesity effects predominating for ALA and anti-inflammatory effects for DHA. Modifying both GLP-1 release and the actions of adipokines by n-3 PUFAs could lead to additive improvements in both insulin secretion and sensitivity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Osteoporosis is a high-prevalence disease, particularly in developed countries, and results in high costs both to the individual and to society through associated fragility fractures. There is an urgent need for identification of novel drug targets and development of new anti-osteoporotic agents. Between 30 and 80% of osteoporotic fractures cannot be prevented despite current treatments achieving relative fracture risk reduction of up to 20%, 50%, and 70% for non-vertebral, hip and spine fractures, respectively. Traditionally, the decline in gonadal hormones has been studied as the sole hormonal determinant for the loss of bone mineral density in osteoporosis. However, recent studies have identified receptors for numerous non-gonadal hormones such as PTH, angiotensin II, leptin, adiponectin, insulin and insulin-like growth factor-1 on the osteoblast lineage cells that directly regulate bone turnover. These hormones are also involved in the pathogenesis of metabolic syndrome risk factors, particularly hypertension, type-II diabetes and obesity. By activating their respective receptors on osteoblastic lineage cells, these hormones appear to act through a common mechanism by down-regulating receptors for activation of nuclear factor kappa B ligand (RANKL) and up-regulating osteoprotegerin (OPG) with inverse responses for adiponectin. Receptors for amylin, gastric inhibitory polypeptide and ghrelin and have also been identified on the osteoblast lineage cells although the roles of these receptors in bone turnover are controversial or poorly studied. Moreover, bone turnover may be independently regulated by modulation of osteoclast-osteoblast function and bone marrow adiposity. Leptin appears to be the only hormone that is a known regulator of both bone mineralisation and bone adiposity.

Black pepper is used worldwide to enhance food flavor. We investigated dietary supplementation with piperine, the active principle of black pepper, to high carbohydrate, high fat (HCHF) diet-fed rats as a model of human metabolic syndrome. Rats were fed with either HCHF diet (carbohydrate, 52%; fat, 24%; 25% fructose in drinking water) or cornstarch (CS) diet for a total of 16 weeks. Diets of the treatment groups (CS + piperine and HCHF + piperine) were supplemented with piperine for the last 8 weeks of this protocol. After 16 weeks, rats fed with HCHF diet developed hypertension, elevated oxidative stress and inflammation-induced cardiac changes (infiltration of inflammatory cells in heart, increase in count and degranulation of mast cells in heart, cardiac fibrosis and increase in ventricular stiffness), reduced responsiveness of aortic rings, impaired glucose tolerance, abdominal obesity together with liver fibrosis, fat deposition and increased plasma liver enzymes. Supplementation with piperine (375 mg/kg food; approximately 30 mg/kg/day) in HCHF-fed rats normalized blood pressure, improved glucose tolerance and reactivity of aortic rings, reduced plasma parameters of oxidative stress and inflammation, attenuated cardiac and hepatic inflammatory cell infiltration and fibrosis and improved liver function. These changes clearly suggest that piperine reduces symptoms of human metabolic syndrome in HCHF-fed rats by reducing inflammation and oxidative stress.

We investigated the changes in adiposity, cardiovascular and liver structure and function, and tissue fatty acid compositions in response to oleic acid-rich macadamia oil, linoleic acid-rich safflower oil and α-linolenic acid-rich flaxseed oil (C18 unsaturated fatty acids) in rats fed either a diet high in simple sugars and mainly saturated fats or a diet high in polysaccharides (cornstarch) and low in fat. The fatty acids induced lipid redistribution away from the abdomen, more pronounced with increasing unsaturation; only oleic acid increased whole-body adiposity. Oleic acid decreased plasma total cholesterol without changing triglycerides and nonesterified fatty acids, whereas linoleic and α-linolenic acids decreased plasma triglycerides and nonesterified fatty acids but not cholesterol. α-Linolenic acid improved left ventricular structure and function, diastolic stiffness and systolic blood pressure. Neither oleic nor linoleic acid changed the left ventricular remodeling induced by high-carbohydrate, high-fat diet, but both induced dilation of the left ventricle and functional deterioration in low fat-diet-fed rats. α-Linolenic acid improved glucose tolerance, while oleic and linoleic acids increased basal plasma glucose concentrations. Oleic and α-linolenic acids, but not linoleic acid, normalized systolic blood pressure. Only oleic acid reduced plasma markers of liver damage. The C18 unsaturated fatty acids reduced trans fatty acids in the heart, liver and skeletal muscle with lowered stearoyl-CoA desaturase-1 activity index; linoleic and α-linolenic acids increased accumulation of their C22 elongated products. These results demonstrate different physiological and biochemical responses to primary C18 unsaturated fatty acids in a rat model of human metabolic syndrome., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We compared the cardiovascular, hepatic and metabolic responses to individual dietary n-3 fatty acids (α-linolenic acid, ALA; eicosapentaenoic acid, EPA; and docosahexaenoic acid, DHA) in a high-carbohydrate, high-fat diet-induced model of metabolic syndrome in rats. Additionally, we measured fatty acid composition of plasma, adipose tissue, liver, heart and skeletal muscle in these rats. The same dosages of ALA and EPA/DHA produced different physiological responses to decrease the risk factors for metabolic syndrome. ALA did not reduce total body fat but induced lipid redistribution away from the abdominal area and favorably improved glucose tolerance, insulin sensitivity, dyslipidemia, hypertension and left ventricular dimensions, contractility, volumes and stiffness. EPA and DHA increased sympathetic activation, reduced the abdominal adiposity and total body fat and attenuated insulin sensitivity, dyslipidemia, hypertension and left ventricular stiffness but not glucose tolerance. However, ALA, EPA and DHA all reduced inflammation in both the heart and the liver, cardiac fibrosis and hepatic steatosis. These effects were associated with complete suppression of stearoyl-CoA desaturase 1 activity. Since the physiological responses to EPA and DHA were similar, it is likely that the effects are mediated by DHA with EPA serving as a precursor. Also, ALA supplementation increased DHA concentrations but induced different physiological responses to EPA and DHA. This result strongly suggests that ALA has independent effects in metabolic syndrome, not relying on its metabolism to DHA., (Copyright © 2013 Elsevier Inc. All rights reserved.)

n-3 polyunsaturated fatty acids (PUFA) have been proposed as potential treatments for human heart failure. The cardioprotective effects of n-3 PUFA are supported by extensive cell culture, animal and human studies. Animal studies with n-3 PUFA have shown marked improvements in many independent risk factors for heart failure, including obesity, type II diabetes, insulin resistance, hypertension and inflammation. However, the evidence from observational studies, randomised controlled trials and meta-analyses that these benefits on risk factors lead to improvements in the symptoms of heart failure in patients is much less convincing. Further, most studies have used marine n-3 PUFA; the role of the plant-derived PUFA, α-linolenic acid (ALA), is even less clear. This discontinuity of scientific evidence from animal to human studies suggests that future studies should focus on defining the optimal dosage range and the efficacy of n-3 PUFA compared to standard treatments using standardised study designs. Further studies on ALA would seem justified.

The population of Sikkim is a unique blend of multi-tribal and metropolitan culture. However, till date, no data regarding prevalence of sexually transmitted diseases (henceforth abbreviated as STDs) among this population is available and hence requires attention. Hence the objective is to determine the prevalence of STDs in Sikkim and to describe associated risk factors. A cross-sectional study involving 'Questionnaire-based anonymous feedback system' was followed to collect data from 2,000 individuals across the society. The four most common STDs, gonorrhea, syphilis, chlamydia and HIV, were considered for the study. Total 69 (3.6%) cases of STDs were found in 1,918 individuals was affected by at least one of the STDs, out of which 43 were males and 26 were females. Cases of gonorrhea, syphilis, chlamydiasis and HIV were 25, 22, 4 and 18 respectively. Out of total 69 cases of STDs, 20 individuals were also suffering from some kind of hepatitis. Addictions like alcoholism, smoking and drugs were also found in significant number, with 1,019 (>50%) individuals with at least one of these addictions. Relative risk analysis indicates that gender-wise females are more vulnerable to STDs than males. The number of partners, addictions, especially alcohol and drug abuse, also contribute to STD cases. STDs act as a significant risk factor in transmitting some of the types of hepatitis. In such cases, females are more vulnerable than males. The results suggest that new community health programs are essential for both, HIV and non-HIV STDs in Sikkim.

Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome.

Obesity, type 2 diabetes, and cardiovascular disease correlate with infiltration to adipose tissue of different immune cells, with uncertain influences on metabolism. Rats were fed a diet high in carbohydrates and saturated fats to develop diet-induced obesity over 16 weeks. This nutritional overload caused overexpression and secretion of phospholipase A(2) group IIA (pla2g2a) from immune cells in adipose tissue rather than adipocytes, whereas expression of adipose-specific phospholipase A(2) (pla2g16) was unchanged. These immune cells produce prostaglandin E(2) (PGE(2)), which influences adipocyte signaling. We found that a selective inhibitor of human pla2g2a (5-(4-benzyloxyphenyl)-(4S)-(phenyl-heptanoylamino)-pentanoic acid [KH064]) attenuated secretion of PGE(2) from human immune cells stimulated with the fatty acid, palmitic acid, or with lipopolysaccharide. Oral administration of KH064 (5 mg/kg/day) to rats fed the high-carbohydrate, high-fat diet prevented the overexpression of pla2g2a and the increased macrophage infiltration and elevated PGE(2) concentrations in adipose tissue. The treatment also attenuated visceral adiposity and reversed most characteristics of metabolic syndrome, producing marked improvements in insulin sensitivity, glucose intolerance, and cardiovascular abnormalities. We suggest that pla2g2a may have a causal relationship with chronic adiposity and metabolic syndrome and that its inhibition in vivo may be a valuable new approach to treat obesity, type 2 diabetes, and metabolic dysfunction in humans.

Age-related physiological changes develop at the same time as the increase in metabolic syndrome in humans after young adulthood. There is a paucity of data in models mimicking chronic diet-induced changes in human middle age and interventions to reverse these changes. This study measured the changes during chronic consumption of a high-carbohydrate (as cornstarch), low-fat (C) diet and a high-carbohydrate (as fructose and sucrose), high-fat (H) diet in rats for 32 wk. C diet feeding induced changes without metabolic syndrome, such as disproportionate increases in total body lean and fat mass, reduced bone mineral content, cardiovascular remodeling with increased systolic blood pressure, left ventricular and arterial stiffness, and increased plasma markers of liver injury. H diet feeding induced visceral adiposity with reduced lean mass, increased lipid infiltration in the skeletal muscle, impaired glucose and insulin tolerance, cardiovascular remodeling, hepatic steatosis, and increased infiltration of inflammatory cells in the heart and the liver. Chia seed supplementation for 24 wk attenuated most structural and functional modifications induced by age or H diet, including increased whole body lean mass and lipid redistribution from the abdominal area, and normalized the chronic low-grade inflammation induced by H diet feeding; these effects may be mediated by increased metabolism of anti-inflammatory n-3 fatty acids from chia seed. These results suggest that chronic H diet feeding for 32 wk mimics the diet-induced cardiovascular and metabolic changes in middle age and that chia seed may serve as an alternative dietary strategy in the management of these changes.

Metabolic syndrome is a risk factor for cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). We investigated the responses to the flavonol, quercetin, in male Wistar rats (8-9 wk old) divided into 4 groups. Two groups were given either a corn starch-rich (C) or high-carbohydrate, high-fat (H) diet for 16 wk; the remaining 2 groups were given either a C or H diet for 8 wk followed by supplementation with 0.8 g/kg quercetin in the food for the following 8 wk (CQ and HQ, respectively). The H diet contained ~68% carbohydrates, mainly as fructose and sucrose, and ~24% fat from beef tallow; the C diet contained ~68% carbohydrates as polysaccharides and ~0.7% fat. Compared with the C rats, the H rats had greater body weight and abdominal obesity, dyslipidemia, higher systolic blood pressure, impaired glucose tolerance, cardiovascular remodeling, and NAFLD. The H rats had lower protein expressions of nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), and carnitine palmitoyltransferase 1 (CPT1) with greater expression of NF-κB in both the heart and the liver and less expression of caspase-3 in the liver than in C rats. HQ rats had higher expression of Nrf2, HO-1, and CPT1 and lower expression of NF-κB than H rats in both the heart and the liver. HQ rats had less abdominal fat and lower systolic blood pressure along with attenuation of changes in structure and function of the heart and the liver compared with H rats, although body weight and dyslipidemia did not differ between the H and HQ rats. Thus, quercetin treatment attenuated most of the symptoms of metabolic syndrome, including abdominal obesity, cardiovascular remodeling, and NAFLD, with the most likely mechanisms being decreases in oxidative stress and inflammation.

Coffee, a rich source of natural products, including caffeine, chlorogenic acid, and diterpenoid alcohols, has been part of the human diet since the 15th century. In this study, we characterized the effects of Colombian coffee extract (CE), which contains high concentrations of caffeine and diterpenoids, on a rat model of human metabolic syndrome. The 8-9 wk old male Wistar rats were divided into four groups. Two groups of rats were fed a corn starch-rich diet whereas the other two groups were given a high-carbohydrate, high-fat diet with 25% fructose in drinking water for 16 wk. One group fed each diet was supplemented with 5% aqueous CE for the final 8 wk of this protocol. The corn starch diet contained ~68% carbohydrates mainly as polysaccharides, whereas the high-carbohydrate, high-fat diet contained ~68% carbohydrates mainly as fructose and sucrose together with 24% fat, mainly as saturated and monounsaturated fat from beef tallow. The high-carbohydrate, high-fat diet-fed rats showed the symptoms of metabolic syndrome leading to cardiovascular remodeling and nonalcoholic fatty liver disease. CE supplementation attenuated impairment in glucose tolerance, hypertension, cardiovascular remodeling, and nonalcoholic fatty liver disease without changing abdominal obesity and dyslipidemia. This study suggests that CE can attenuate diet-induced changes in the structure and function of the heart and the liver without changing the abdominal fat deposition.

Chia seeds contain the essential fatty acid, α-linolenic acid (ALA). This study has assessed whether chia seeds attenuated the metabolic, cardiovascular and hepatic signs of a high-carbohydrate, high-fat (H) diet [carbohydrates, 52% (wt/wt); fat, 24% (wt/wt) with 25% (wt/vol) fructose in drinking water] in rats. Diets of the treatment groups were supplemented with 5% chia seeds after 8 weeks on H diet for a further 8 weeks. Compared with the H rats, chia seed-supplemented rats had improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis and reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure. Chia seeds induced lipid redistribution with lipid trafficking away from the visceral fat and liver with an increased accumulation in the heart. The stearoyl-CoA desaturase-1 products were depleted in the heart, liver and the adipose tissue of chia seed-supplemented rats together with an increase in the substrate concentrations. The C18:1trans-7 was preferentially stored in the adipose tissue; the relatively inert C18:1n-9 was stored in sensitive organs such as liver and heart and C18:2n-6, the parent fatty acid of the n-6 pathway, was preferentially metabolized. Thus, chia seeds as a source of ALA induce lipid redistribution associated with cardioprotection and hepatoprotection., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Epidemiological, human, animal, and cell culture studies show that n-3 fatty acids, especially α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), reduce the risk factors of cardiovascular diseases. EPA and DHA, rather than ALA, have been the focus of research on the n-3 fatty acids, probably due to the relatively inefficient conversion of ALA to EPA and DHA in rodents and humans. This review will assess our current understanding of the effects and potential mechanisms of actions of individual n-3 fatty acids on multiple risk factors of metabolic syndrome. Evidence for pharmacological responses and the mechanism of action of each of the n-3 fatty acid trio will be discussed for the major risk factors of metabolic syndrome, especially adiposity, dyslipidemia, insulin resistance and diabetes, hypertension, oxidative stress, and inflammation. Metabolism of n-3 and n-6 fatty acids as well as the interactions of n-3 fatty acids with nutrients, gene expression, and disease states will be addressed to provide a rationale for the use of n-3 fatty acids to reduce the risk factors of metabolic syndrome., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Stearoyl-CoA desaturase 1 (SCD-1) is the rate-limiting enzyme that catalyses the conversion of saturated to monounsaturated fatty acids. Increased SCD-1 expression and activity has been implicated in cancer, cardiovascular diseases, insulin resistance and obesity. Studies with humans, wild-type rodents, knock-out mice and cells in culture show that SCD-1 inhibition decreases lipogenesis and increases GLUT4-mediated glucose uptake in skeletal muscle. In this review, we will evaluate the role of SCD-1 as a homeostatic check-point between glucose and fatty acid metabolism in the development and progression of obesity. In addition to the role of SCD-1 in glucose and fatty acid metabolism, we will also discuss the expression and regulation of SCD-1, its specific interactions with inflammatory responses and PPARs, the role of SCD-1 derived MUFAs in obesity and the relevance of SCD desaturation index as a predictor of obesity and metabolic syndrome. Additionally, we will explore the prospects of SCD-1 as a potential drug target for the management of obesity and related disorders.

Metabolic syndrome (obesity, diabetes, and hypertension) increases hepatic and cardiovascular damage. This study investigated preventive or reversal responses to rutin in high-carbohydrate, high-fat diet-fed rats as a model of metabolic syndrome. Rats were divided into 6 groups: 2 groups were fed a corn starch-rich diet for 8 or 16 wk, 2 groups were fed a high-carbohydrate, high-fat diet for 8 or 16 wk, and 2 groups received rutin (1.6 g/kg diet) in either diet for the last 8 wk only of the 16-wk protocol. Metabolic changes and hepatic and cardiovascular structure and function were then evaluated in these rats. The corn starch-rich diet contained 68% carbohydrate (mainly cornstarch) and 0.7% fat, whereas the high-carbohydrate, high-fat diet contained 50% carbohydrate (mainly fructose) and 24% fat (mainly beef tallow) along with 25% fructose in drinking water (total 68% carbohydrate using mean food and water intakes). The high-carbohydrate, high-fat diet produced obesity, dyslipidemia, hypertension, impaired glucose tolerance, hepatic steatosis, infiltration of inflammatory cells in the liver and the heart, higher cardiac stiffness, endothelial dysfunction, and higher plasma markers of oxidative stress with lower expression of markers for oxidative stress and apoptosis in the liver. Rutin reversed or prevented metabolic changes such as abdominal fat pads and glucose tolerance, reversed or prevented changes in hepatic and cardiovascular structure and function, reversed oxidative stress and inflammation in the liver and heart, and normalized expression of liver markers. These results suggest a non-nutritive role for rutin to attenuate chronic changes in metabolic syndrome.

The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.

The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.

Anthocyanins, phenolic acids and carotenoids are the predominant phytochemicals present in purple carrots. These phytochemicals could be useful in treatment of the metabolic syndrome since anthocyanins improve dyslipidaemia, glucose tolerance, hypertension and insulin resistance; the phenolic acids may also protect against CVD and β-carotene may protect against oxidative processes. In the present study, we have compared the ability of purple carrot juice and β-carotene to reverse the structural and functional changes in rats fed a high-carbohydrate, high-fat diet as a model of the metabolic syndrome induced by diet. Cardiac structure and function were defined by histology, echocardiography and in isolated hearts and blood vessels; liver structure and function, oxidative stress and inflammation were defined by histology and plasma markers. High-carbohydrate, high-fat diet-fed rats developed hypertension, cardiac fibrosis, increased cardiac stiffness, endothelial dysfunction, impaired glucose tolerance, increased abdominal fat deposition, altered plasma lipid profile, liver fibrosis and increased plasma liver enzymes together with increased plasma markers of oxidative stress and inflammation as well as increased inflammatory cell infiltration. Purple carrot juice attenuated or reversed all changes while β-carotene did not reduce oxidative stress, cardiac stiffness or hepatic fat deposition. As the juice itself contained low concentrations of carotenoids, it is likely that the anthocyanins are responsible for the antioxidant and anti-inflammatory properties of purple carrot juice to improve glucose tolerance as well as cardiovascular and hepatic structure and function.

Olive oil, an important component of the Mediterranean diet, produces cardioprotective effects, probably due to both oleic acid and the polyphenols such as oleuropein and hydroxytyrosol. Our aim in this study was to assess whether a polyphenol-enriched extract from the leaves of Olea europaea L. with oleuropein as the major component attenuated the cardiovascular, hepatic, and metabolic signs of a high-carbohydrate, high-fat (HCHF) diet (carbohydrate, 52%; fat, 24%, 25% fructose in drinking water) in rats. Male Wistar rats were fed either a cornstarch diet (CS) or a HCHF diet for a total of 16 wk. Diets of the treatment groups [CS+olive leaf extract (OLE) and HCHF+OLE] were supplemented with 3% OLE after 8 wk of being fed their respective CS or HCHF diets for a further 8 wk. After 16 wk, HCHF rats developed signs of metabolic syndrome, including elevated abdominal and hepatic fat deposition, collagen deposition in heart and liver, cardiac stiffness, and oxidative stress markers (plasma malondialdehyde and uric acid concentrations), with diminished aortic ring reactivity, abnormal plasma lipid profile, impaired glucose tolerance, and hypertension. Compared with HCHF rats, those in the HCHF+OLE group had improved or normalized cardiovascular, hepatic, and metabolic signs with the exception of elevated blood pressure. These results strongly suggest that an OLE containing polyphenols such as oleuropein and hydroxytyrosol reverses the chronic inflammation and oxidative stress that induces the cardiovascular, hepatic, and metabolic symptoms in this rat model of diet-induced obesity and diabetes without changing blood pressure.

Unlabelled: Spices used in Indian cooking have a long history of use as medicines to prevent and treat diseases. Many studies have confirmed that spices can be useful medicines, but the major challenge is now to provide scientific evidence and plausible mechanisms for their therapeutic responses. This review focuses on the therapeutic potential of Indian spices to treat multiple symptoms of the metabolic syndrome such as insulin resistance, diabetes, obesity, altered lipid profile and hypertension. The metabolic syndrome is prevalent and has become an important financial burden to the healthcare system in both developed and developing countries. Inflammation and oxidative stress have been proposed as initiators of the metabolic syndrome, especially of insulin resistance. Natural products with anti-inflammatory and anti-oxidant properties are found in spices. Adequate doses of these compounds may be effective in treating the metabolic syndrome. Testing these potential treatments requires adequate animal models, usually rodents, so the limitations of these models are important. Furthermore, this review highlights the need for adequate legislation and regulation to ensure the safety and success of evidence-based functional foods and nutraceuticals., Keywords: Spices, Diabetes, Cardiovascular disease, Metabolic syndrome, Inflammation, Oxidative stress,