Immunotherapy and cardiovascular diseases: novel avenues for immunotherapeutic approaches.

As current therapies for cardiovascular disease (CVD), predominantly based on lipid lowering, still face an unacceptable residual risk, novel treatment strategies are being explored. Besides lipids, inflammatory processes play a major role in the pathogenesis of atherosclerosis, the underlying cause of the majority of CVD. The first clinical trials targeting the interleukin-1ß-inflammasome axis have shown that targeting this pathway is successful in reducing cardiovascular events but did not decrease overall CVD mortality. Hence, novel and improved immunotherapeutics to treat CVD are being awaited.

Determinants of weight, psychological status, food contemplation and lifestyle changes in patients with obesity during the COVID-19 lockdown: a nationwide survey using multiple correspondence analysis.

INTRODUCTION: The corona virus disease 2019 (COVID-19) pandemic forced most of the Italian population into lockdown from 11 March to 18 May 2020. A nationwide survey of Italian Clinical Nutrition and Dietetic Services (Obesity Centers or OCs) was carried out to assess the impact of lockdown restrictions on the physical and mental wellbeing of patients with obesity (PWO) who had follow-up appointments postponed due to lockdown restrictions and to compare determinants of weight gain before and after the pandemic. METHODS: We designed a structured 77-item questionnaire covering employment status, diet, physical activity and psychological aspects, that was disseminated through follow-up calls and online between 2 May and 25 June 2020. Data were analyzed by multiple correspondence analysis (MCA) and multiple linear regression. RESULTS: A total of 1,232 PWO from 26 OCs completed the questionnaires (72% female, mean age 50.2 ± 14.2 years; mean BMI 34.7 ± 7.6 kg/m2; 41% obesity class II to III). During the lockdown, 48.8% gained, 27.1% lost, while the remainder (24.1%) maintained their weight. The mean weight change was +2.3 ± 4.8 kg (in weight gainers: +4.0 ± 2.4 kg; +4.2% ± 5.4%). Approximately 37% of participants experienced increased emotional difficulties, mostly fear and dissatisfaction. Sixty-one percent reduced their physical activity (PA) and 55% experienced a change in sleep quality/quantity. The lack of online contact (37.5%) with the OC during lockdown strongly correlated with weight gain (p < 0.001). Using MCA, two main clusters were identified: those with unchanged or even improved lifestyles during lockdown (Cluster 1) and those with worse lifestyles during the same time (Cluster 2). The latter includes unemployed people experiencing depression, boredom, dissatisfaction and increased food contemplation and weight gain. Within Cluster 2, homemakers reported gaining weight and experiencing anger due to home confinement. CONCLUSIONS: Among Italian PWO, work status, emotional dysregulation, and lack of online communication with OCs were determinants of weight gain during the lockdown period.

Effect of a Low Glycemic Index Mediterranean Diet on Non-Alcoholic Fatty Liver Disease. A Randomized Controlled Clinici Trial.

INTRODUCTION: Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common form of liver disease worldwide affecting all ages and ethnic groups and it has become a consistent threat even in young people. Our aim was to estimate the effect of a Low Glycemic Index Mediterranean Diet (LGIMD) on the NAFLD score as measured by a Liver Ultrasonography (LUS). DESIGN: NUTRIzione in EPAtologia (NUTRIEPA) is a population-based Double-Blind RCT. Data were collected in 2011 and analyzed in 2013-14. SETTING/PARTICIPANTS: 98 men and women coming from Putignano (Puglia, Southern Italy) were drawn from a previous randomly sampled population-based study and identified as having moderate or severe NAFLD. INTERVENTION: The intervention strategy was the assignment of a LGIMD or a control diet. OUTCOME MEASURES: The main outcome measure was NAFLD score, defined by LUS. RESULTS: After randomization, 50 subjects were assigned to a LGIMD and 48 to a control diet. The study lasted six months and all participants were subject to monthly controls/checks. Adherence to the LGIMD as measured by Mediterranean Adequacy Index (MAI) showed a median of 10.1. A negative interaction between time and LGIMD on the NAFLD score (-4.14, 95% CI -6.78,-1.49) was observed, and became more evident at the sixth month (-4.43, 95%CI -7.15, -1.71). A positive effect of the interaction among LGIMD, time and age (Third month: 0.07, 95% CI 0.02, 0.12; Sixth month: 0.08, 95% CI 0.03,0.13) was also observed. CONCLUSIONS: LGIMD was found to decrease the NAFLD score in a relatively short time. Encouraging those subjects who do not seek medical attention but still have NAFLD to follow a LGIMD and other life-style interventions, may reduce the degree of severity of the disease. Dietary intervention of this kind, could also form the cornerstone of primary prevention of Type 2 Diabetes Mellitus (T2DM) and cardiovascular disease.

Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review.

A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer's disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD.

High serum resistin in chronic viral hepatitis is not a marker of metabolic disorder.

BACKGROUND/AIMS: The role of resistin, an adipocyte-secreted hormone, in insulin resistance and in inflammation is controversial. In chronic hepatitis C, insulin resistance, type 2 diabetes and liver steatosis are frequent and inconsistently correlated to circulating resistin levels. In this study we assessed if viral aetiology and host metabolic parameters influence serum resistin in patients with HCV- and HBV- related chronic hepatitis. METHODOLOGY: Serum resistin was measured by ELISA and correlated to viral aetiology, age, gender, BMI, HOMA-IR, liver steatosis, hepatitis staging and grading, blood glucose, triglycerides and cholesterol in 43 patients with chronic hepatitis C, in 16 with chronic hepatitis B and in 29 healthy controls. RESULTS: In both groups of patients resistin was significantly higher than in controls, with higher values in HBV- than in HCV-patients (p = 0.0007). Resistin levels were correlated to aetiology and, inversely, to age (p = 0.026), diabetes (p = 0.036) and steatosis (p = 0.029). Multiple regression analysis showed that resistin concentration was dependent only on the aetiology of liver disease (p = 0.001). CONCLUSIONS: In chronic viral hepatitis serum resistin levels are high and not associated with altered metabolic parameters or with the histological activity of the disease. The meaning of higher resistin in HBV- than in HCV- chronic hepatitis is unclear.

Metabolic syndrome, psychological status and quality of life in obesity: the QUOVADIS Study.

OBJECTIVE: We aimed to investigate the association of the clinical variables of the metabolic syndrome (MS) and psychological parameters on health-related quality of life (HRQL) in obesity. In particular, our aim was to investigate the relative impact of physical symptoms, somatic diseases and psychological distress on both the physical and the mental domains of HRQL. DESIGN: Cross-sectional study. SUBJECTS: A cohort of 1822 obese outpatients seeking treatment in medical centers. MEASUREMENTS: HRQL was measured by the standardized summary scores for physical (PCS) and mental (MCS) components of the Short Form 36 Health Survey (SF-36). Patients were grouped according to tertiles of PCS and MCS. Metabolic and psychological profiles of PCS and MCS tertiles were compared by discriminant analysis. RESULTS: The profile of metabolic and psychological variables was tertile-specific in 62.4 and 68.3% of patients in the lowest and highest tertiles of PCS, respectively, while concordance was low in the mid-tertile (32.8%). Concordance was very high in the lowest (74.4%) and in the highest (75.5%) tertiles of MCS, and was fair in the mid-tertile (53.2%). The main correlates of PCS were obesity-specific and general psychological well-being, BMI, body uneasiness, binge eating, gender and psychiatric distress. Only hypertension and hyperglycemia qualified as correlates among the components of MS. The components of MS did not define MCS. CONCLUSIONS: Psychological well-being is the most important correlate of HRQL in obesity, both in the physical and in the mental domains, whereas the features of MS correlate only to some extent with the physical domain of HRQL.

Prognostic factors of survival in complicated viral and alcoholic cirrhosis without hepatocellular carcinoma. A retrospective study.

AIM: In several studies, attention is needed to one specific complication, in particularly to hepatocellular carcinoma, which modifies the natural history of liver cirrhosis. Thus, we performed a retrospective cohort analysis to clarify which complications, alone or in combination, are predictive factors of mortality in patients with viral or alcoholic cirrhosis without hepatocellular carcinoma. METHODS: Case records of 255 patients with decompensated viral or alcoholic cirrhosis between January 1990 and December 2000 were retrospectively analyzed. Relevant clinical and laboratory parameters, and their relationship to mortality, were studied. RESULTS: The mean duration of follow-up period was 29 months in which 178 patients (69.8%) died and 77 (31.8%) survived. None of the patients underwent liver transplantation. The cumulative mortality rate of patients with complicated cirrhosis was 38.8% after 1 year, 51.7% after 2 years, 61.1% after 3 years and 65.1% after 8 years. A multivariate Cox's model identified the following variables as significant: age (P=0.001), gastrointestinal bleeding (GB)-ascites combination (P=0.000), encephalopathy-GB-ascites (P=0.028), hepatorenal syndrome (HRS) (P=0.000), GB-spontaneous bacterial peritonitis (SBP) (P=0.001), alkaline phosphatase (ALP) (P=0.004) and the Child-Pugh score (P=0.000). CONCLUSION: The mortality in a group of patients with alcoholic cirrhosis is longer than in those with viral cirrhosis . Moreover, ascites in combination with other complications, HRS and hemorrage-SBP association are independent predictors of mortality in patients with complicated liver cirrhosis.

Efficient syntheses, human and yeast farnesyl-protein transferase inhibitory activities of chaetomellic acids and analogues.

Chaetomellic acids are a class of alkyl dicarboxylic acids that were isolated from Chaetomella acutiseta. They are potent and highly specific farnesyl-pyrophosphate (FPP) mimic inhibitors of Ras farnesyl-protein transferase. We have previously described the first biogenetic type aldol condensation-based total synthesis of chaetomellic acid A. Modification of the later steps of that synthesis resulted in the efficient syntheses of chaetomellic acids A and B in three steps with 75-80% overall yield. In this report, details of the original total syntheses of chaetomellic acids A, B and C, the new syntheses of acids A and B and structure-activity relationship of these compounds against various prenyl transferases including human and yeast FPTase and bovine and yeast GGPTase I are described. Chaetomellic acids are differentially active against human and yeast FPTase. Chaetomellic acid A inhibited human and yeast FPTase activity with IC50 values of 55 nM and 225 microM, respectively. In contrast, chaetomellic acid C showed only a 10-fold differential in inhibitory activities against human versus yeast enzymes. In keeping with molecular modeling-based predictions, the compounds with shorter alkyl side chains (C-8) were completely inactive against FPTase.

Prognostic value of low density lipoprotein receptor expression in colorectal carcinoma.

Cancer cells require more cholesterol than normal cells. This requirement seems to be satisfied by a higher HMG-CoA reductase activity or a higher activity of low density lipoprotein receptor (LDLR). We investigated the prognostic value of LDLR in colorectal carcinoma (CRC) patients. The LDLR was evaluated in 90 patients with CRC by ELISA. The survival time and the relative risk of prognostic factors were analyzed by Kaplan-Meier estimates and Cox proportional hazard model. Thirty three cases were LDLR positive (+), while 57 LDLR negative (-). The survival of LDLR(-) patients was shorter than that of LDLR(+). By Cox model, the absence of LDLR and time until metastasis resulted significantly associated with the CRC-related survival. The absence of LDLR in CRC predicts a shorter survival.

A sensitive and specific PCR method to detect Helicobacter felis in a conventional mouse model.

Although many detection methods have been used to determine Helicobacter colonization in small animal models, the sensitivity and specificity of these detection methods are limited. To improve the Helicobacter felis conventional mouse model for accurate evaluation of therapeutic regimens, we developed a PCR for detection of, and a competitive PCR for quantitation of, H. felis in viral antibody-free (VAF) mice. The PCR was based on the H. felis 16S rRNA gene. An internal control DNA was used for competitive quantitation of the PCR. VAF conventional Swiss-Webster mice were infected with an H. felis culture by oral gavage. At various times after H. felis challenge and therapy, stomach mucosa was collected and evaluated by PCR. PCR detected approximately 50 to 100 H. felis cells per mouse stomach and showed no cross-reaction with other bacteria commonly found in mouse stomachs. Colonization of H. felis in the mouse stomach was confirmed by culture isolation from germfree mice and histological examination of VAF mice. Response to therapy in this H. felis model correlated well with results seen in human clinical trials with H. pylori. A model utilizing PCR detection which may be useful for discovering new antibiotics and/or vaccines against Helicobacter ulcer disease has been developed.

[The clinical aspects of 49 cases of early gastric cancer]. / Considerazioni cliniche su 49 casi di Early Gastric Cancer.

Forty-nine consecutive patients with early gastric cancer (EGC), observed from January 1978 to December 1992 in the Surgery Department of our Institute, were included in a retrospective study. The EGC prevalence in the overall cases of gastric cancer was 11%. This frequency was 8% in the period 1978-1985 and 15% in the period 1986-1992. All patients underwent gastroscopy with gastric biopsy, but only in 35 cases (72%) was a preoperative diagnosis of gastric cancer possible. In the remaining 14 cases only the histological examination of surgical specimens made possible a definitive diagnosis. A subtotal gastrectomy was carried out in 36 cases (73%), a total gastrectomy in 12 cases (25%) while only in one case (2%) was a superior polar resection carried out. The postoperative morbidity was 5% and mortality was 2%. The median survival was 61 months and, at the moment, 41 patients are alive and free from disease. Our data confirm the favourable prognosis of EGC compared to the advanced gastric cancer. We think it useful to carry out a routine gastroscopy when there are symptoms related to the upper abdomen in order to make an early diagnosis of gastric cancer.

Familial risk of colo-rectal cancer in a low incidence area in southern Italy.

The risk of colo-rectal cancer (CRC) in subjects with a positive family history (FH+) for malignancy has been assessed by means of a case-control study carried out between 1987-89 in an area of about 215,000 inhabitants in Southern Italy. One hundred and nineteen CRC cases were compared with 119 sex- and age-frequency matched population controls. Detailed pedigrees were collected at the family homes of both cases and controls. The odds ratio (OR) of CRC, adjusted by means of logistic regression for age, sex and number of first-degree relatives, increased with the number of any kinds of cancers in first-degree relatives with a significant linear trend (p = 0.042), while there was no risk with a FH+ for digestive cancer excluding CRC or for other cancers excluding large bowel and digestive organs. The OR (and 95% confidence interval) for CRC was 5.9 (1.64-21.23) for at least one first-degree relative with CRC. After a mutual adjustment between CRC and the other cancers in the families of cases and controls, the risk of CRC with a FH+ for other cancers did not change, revealing a strong association (p = 0.002) for CRC alone. From the analysis of the family history of cancer in the case group, the relative frequency of families that satisfied the criteria for so-called hereditary non-polyposic colo-rectal cancer (HNPCC) was 2.6%. The increased relative risk of CRC observed only in families with FH+ for CRC is a supportive finding for organizing and planning prevention and genetic counselling for these families, whose members should be referred for further assessment.