Dietary and Smoking Acrylamide and Prostate Cancer Risk: CAPLIFE Study.

Acrylamide is a probable carcinogen. Its main sources are the diet and tobacco. The association between acrylamide intake from the diet and tobacco and prostate cancer (PCa) has not been previously evaluated. We aimed to evaluate the relationship between dietary acrylamide intake and exposure to acrylamide through cigarettes and PCa risk. A population-based case-control (CAPLIFE) study was conducted, including 428 incident PCa cases and 393 controls. Smoking and dietary information, with a validated food frequency questionnaire, was collected. We calculated the amount of acrylamide from both sources, and tertiles (Ts) were created. Multivariable logistic regression and restricted cubic spline models were applied to assess the association between exposure to acrylamide and PCa risk. The median was similar for acrylamide in both dietary and smoking acrylamide among PCa cases and controls. No association was observed between dietary acrylamide intake and overall PCa risk (adjusted ORT3vsT1 = 0.90 (95% CI 0.59, 1.37)). A risk trend was observed for acrylamide exposure from cigarette smoking (p-trend = 0.032), with the highest odds in those subjects with the high exposure to acrylamide through cigarettes (adjusted ORT3vsT1 = 1.67 (95% CI 0.92, 3.04)). The restricted cubic splines suggested a linear relationship. In conclusion, acrylamide from smoking could be positively associated with PCa risk, but no association was observed for dietary acrylamide.

The duration of intervals on the oral cancer care pathway and implications for survival: a systematic review and meta-analysis.

Introduction: Previous studies measuring intervals on the oral cancer care pathway have been heterogenous, showing mixed results with regard to patient outcomes. The aims of this research were (1) to calculate pooled meta-analytic estimates for the duration of the patient, diagnostic and treatment intervals in oral cancer, considering the income level of the country, and (2) to review the evidence on the relationship of these three intervals with tumor stage at diagnosis and survival. Materials and methods: We conducted a systematic review with meta-analysis following PRISMA 2020 guidelines (pre-registered protocol CRD42020200752). Following the Aarhus statement, studies were eligible if they reported data on the length of the patient (first symptom to first presentation to a healthcare professional), diagnostic (first presentation to diagnosis), or treatment (diagnosis to start of treatment) intervals in adult patients diagnosed with primary oral cancer. The risk of bias was assessed with the Aarhus checklist. Results: Twenty-eight studies reporting on 30,845 patients met the inclusion criteria. The pooled median duration of the patient interval was 47 days (95% CI = 31-73), k = 18, of the diagnosis interval 35 days (95% CI = 21-38), k = 11, and of the treatment interval 30 days (95% CI = 23-53), k = 19. In lower-income countries, the patient and treatment intervals were significantly longer, and longer patient intervals were related to later stage at diagnosis. In studies with a lower risk of bias from high-income countries, longer treatment intervals were associated with lower survival rates. Conclusion: Interval duration on the oral cancer care pathway is influenced by the socio-economic context and may have implications for patient outcomes.

Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis.

Background: Despite the fact that several studies have investigated the association between serum copper levels (S-Cu) and the risk of cardiovascular diseases, this relationship remains unclear. The aims of this study were to investigate the association between S-Cu and risk of major adverse cardiovascular events (MACE), including total stroke, ischemic stroke, hemorrhagic stroke, myocardial infarction and cardiovascular mortality, and identify potential sources of results heterogeneity. Methods: We carried out a systematic review and meta-analysis. The selection criteria were: (1) Observational studies (cohort studies, case-control studies and hybrid studies); (2) Studies containing quantitative data about the relationship between S-Cu and risk of MACE; (3) Estimating association measures; and (4) Studies written in English, French or Spanish. Overall pooled Odds ratio (pOR) and 95% confidence intervals (95% CI) of MACE for the highest vs. lowest S-Cu category were calculated using random-effects models. Results: Sixteen studies with a total of 41,322 participants were included in the meta-analysis: 10 prospective cohort studies, 5 nested case-control studies and 1 case-control study. Comparing highest vs. lowest category, high S-Cu levels were associated with total stroke (pOR: 1.49, 95% CI 1.22-1.82; I2 = 0%, p = 0.54), myocardial infarction (pOR: 1.31, 95% CI 1.17-1.46; I2 = 0.0%, p = 0.92) and cardiovascular mortality (pOR: 1.60, 95% CI 1.39-1.86; I2 = 0.0%, p = 0.54). Subgroup analysis showed that studies with a hybrid design had higher risks for cardiovascular mortality (pOR: 3.42, 95% CI 1.98-5.92) and ischemic stroke (pOR: 1.54, 95% CI 1.30-1.83). Conclusion: High S-Cu levels were associated with an increased risk of total stroke, myocardial infarction and cardiovascular mortality. Hybrid studies seems to modify the strength of the association between S-Cu and the risk of cardiovascular mortality and ischemic stroke. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370782], identifier [CRD42022370782].

Ejaculation Frequency and Prostate Cancer: CAPLIFE Study.

PURPOSE: To evaluate the association between ejaculation frequency (EF) during four stages of life and prostate cancer (PCa) according to tumor aggressiveness, PCa stage, and urinary symptomatology. MATERIALS AND METHODS: A total of 456 incident PCa cases histologically confirmed, and 427 controls aged 40-80 years from the CAPLIFE study were analyzed. This study is a population-based case-control study carried out in the south of Spain. Average EF was measured for: (1) 20s, (2) 30s, (3) 40s, and (4) one year before the interview. EF was categorized into: (1) 0-3, (2) 4, and (3) >4 ejaculations/month. Sociodemographic, lifestyle, and medical information were also collected. To estimate the association between EF and PCa, adjusted ORs (aORs) and 95% CIs were calculated by logistic regression models. RESULTS: A year before the interview, PCa cases ejaculated less frequently than the controls. An inverse association was observed between the EF a year before and PCa, aOR=1.64 (95% CI 1.03-2.61) for men with 4 ejaculations/month, and aOR=2.38 (95% CI 1.57-3.60) for men with 0-3 ejaculations/month, compared to men with >4. The association was higher for cases with ISUP 3-5 (aOR=2.76 [95% CI 1.34-5.67] for men with 0-3 ejaculations/month) or with a locally advanced-metastatic tumor (aOR=4.70 [95% CI 1.55-14.29]). Moreover, men with moderate urinary symptoms and 0-3 ejaculations/month had the highest risk, aOR=3.83 (95% CI 1.84-7.95). CONCLUSIONS: A low EF could be associated with a higher risk of PCa, especially for cases with ISUP 3-5 or with a locally advanced-metastatic tumor.

Influencia de la dieta en el riesgo de infección y de gravedad de la COVID-19: una revisión sistemática / Influence of diet in COVID-19 infection and severity risk: a systematic review

Introducción: el riesgo y/o el pronóstico de la COVID-19, causado por el virus SARS-CoV-2, se han relacionado con enfermedades crónicas como obesidad, diabetes mellitus y enfermedades cardiovasculares, siendo la dieta de mala calidad un factor predisponente para estas enfermedades. Objetivo: sintetizar la evidencia científica sobre el efecto de la dieta en el riesgo de infección por SARS-CoV-2 y de COVID-19 grave. Métodos: revisión sistemática realizada siguiendo las guías PRISMA. La búsqueda bibliográfica se hizo en las bases de datos Web of Science, Scopus y Medline (a través del buscador PubMed). El análisis del riesgo de sesgo se realizó mediante las escalas Newcastle-Ottawa y Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Resultados: se incluyeron 14 estudios. Una buena adherencia a la dieta mediterránea se asoció con una disminución del riesgo de infección por SARS-CoV-2 (razón de momios RM = 0,44; IC 95 %: 0,22-0,88, para adherencia alta versus baja, y RM significativas de 0,88 y 0,95 en los estudios que analizaron la adherencia de forma cuantitativa) pero no con la gravedad de la COVID-19. Una dieta basada en plantas presentó una asociación protectora frente a la infección y la enfermedad grave. Concretamente, un alto consumo de verdura, legumbres y cereales, y una baja ingesta de lácteos y carnes rojas mostraron un efecto protector frente a la infección y/o la COVID-19 grave, según el estudio. Los suplementos vitamínicos y probióticos también disminuyeron el riesgo de infección. Conclusión: la evidencia disponible sugiere que una dieta saludable, basada en un patrón de dieta mediterránea o en alimentos vegetales, con consumo de lácteos y carnes rojas moderado, ejerce un efecto protector frente a la COVID-19. (AU)

Introduction: the risk and/or prognosis of COVID-19, caused by the SARS-CoV-2 virus, have been related to chronic diseases such as obesity, diabetes mellitus, and cardiovascular diseases, with poor-quality diet being a predisposing factor for these diseases. Objective: to synthesize the scientific evidence on the effect of diet on the risk of SARS-CoV-2 infection and severe COVID-19. Methods: a systematic review was carried out following the PRISMA guidelines. The bibliographic search was made in the databases Web of Science, Scopus and Medline (through the PubMed search engine). Risk of bias analysis was performed using the Newcastle-Ottawa and Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies scales. Results: 14 studies were included. Good adherence to the Mediterranean diet was associated with a decreased risk of SARS-CoV-2 infection (OR = 0.44; 95 % CI, 0.22-0.88, for high versus low adherence, and significant ORs of 0.88 and 0.95 in studies that analyzed adherence quantitatively) but not with the severity of COVID-19. A plant-based diet also had a protective association against both COVID-19 infection and severity. Specifically, a high consumption of vegetables, legumes and cereals, and a low intake of dairy products and red meat showed a protective effect against infection and/or COVID-19 severity, depending on the study. Vitamin and probiotic supplements also lowered the risk of infection. Conclusion: the available evidence suggests that a healthy diet, based on a Mediterranean or plant-based diet, with moderate consumption of dairy and red meat, exerts a protective effect against COVID-19. (AU)

[Influence of diet in COVID-19 infection and severity risk: a systematic review]. / Influencia de la dieta en el riesgo de infección y de gravedad de la COVID-19: una revisión sistemática.

Introduction: Introduction: the risk and/or prognosis of COVID-19, caused by the SARS-CoV-2 virus, have been related to chronic diseases such as obesity, diabetes mellitus, and cardiovascular diseases, with poor-quality diet being a predisposing factor for these diseases. Objective: to synthesize the scientific evidence on the effect of diet on the risk of SARS-CoV-2 infection and severe COVID-19. Methods: a systematic review was carried out following the PRISMA guidelines. The bibliographic search was made in the databases Web of Science, Scopus and Medline (through the PubMed search engine). Risk of bias analysis was performed using the Newcastle-Ottawa and Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies scales. Results: 14 studies were included. Good adherence to the Mediterranean diet was associated with a decreased risk of SARS-CoV-2 infection (OR = 0.44; 95 % CI, 0.22-0.88, for high versus low adherence, and significant ORs of 0.88 and 0.95 in studies that analyzed adherence quantitatively) but not with the severity of COVID-19. A plant-based diet also had a protective association against both COVID-19 infection and severity. Specifically, a high consumption of vegetables, legumes and cereals, and a low intake of dairy products and red meat showed a protective effect against infection and/or COVID-19 severity, depending on the study. Vitamin and probiotic supplements also lowered the risk of infection. Conclusion: the available evidence suggests that a healthy diet, based on a Mediterranean or plant-based diet, with moderate consumption of dairy and red meat, exerts a protective effect against COVID-19.

Introducción: Introducción: el riesgo y/o el pronóstico de la COVID-19, causado por el virus SARS-CoV-2, se han relacionado con enfermedades crónicas como obesidad, diabetes mellitus y enfermedades cardiovasculares, siendo la dieta de mala calidad un factor predisponente para estas enfermedades. Objetivo: sintetizar la evidencia científica sobre el efecto de la dieta en el riesgo de infección por SARS-CoV-2 y de COVID-19 grave. Métodos: revisión sistemática realizada siguiendo las guías PRISMA. La búsqueda bibliográfica se hizo en las bases de datos Web of Science, Scopus y Medline (a través del buscador PubMed). El análisis del riesgo de sesgo se realizó mediante las escalas Newcastle-Ottawa y Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Resultados: se incluyeron 14 estudios. Una buena adherencia a la dieta mediterránea se asoció con una disminución del riesgo de infección por SARS-CoV-2 (razón de momios RM = 0,44; IC 95 %: 0,22-0,88, para adherencia alta versus baja, y RM significativas de 0,88 y 0,95 en los estudios que analizaron la adherencia de forma cuantitativa) pero no con la gravedad de la COVID-19. Una dieta basada en plantas presentó una asociación protectora frente a la infección y la enfermedad grave. Concretamente, un alto consumo de verdura, legumbres y cereales, y una baja ingesta de lácteos y carnes rojas mostraron un efecto protector frente a la infección y/o la COVID-19 grave, según el estudio. Los suplementos vitamínicos y probióticos también disminuyeron el riesgo de infección. Conclusión: la evidencia disponible sugiere que una dieta saludable, basada en un patrón de dieta mediterránea o en alimentos vegetales, con consumo de lácteos y carnes rojas moderado, ejerce un efecto protector frente a la COVID-19.

Prevalence of frailty and its association with oral hypofunction in older adults: a gender perspective.

BACKGROUND: Previous studies have indicated an association between oral hypofunction and frailty in community-dwelling older adults. However, this issue has not been evaluated in institutionalized older patients. We aimed to determine the prevalence of physical frailty in this particularly vulnerable group and evaluate its association with oral hypofunction, analyzing possible differences by gender. METHODS: This cross-sectional study was conducted in private and public care homes in Guayaquil (Ecuador) from January 2018 until December 2019. Participants were classified as robust, pre-frail, and frail according to the Fried's frailty phenotype. Oral hypofunction was defined as the presence of at least three positive items in the following list: poor oral hygiene, oral dryness, reduced occlusal force, decreased masticatory function, and deterioration of swallowing function. The relationships between frailty and oral hypofunction were analyzed using logistic regression models for the whole sample and stratified by gender. Statistical analyses were performed using STATA 15.0 software (Stata Corp. LP, College Station, TX, USA). RESULTS: Among the 589 participants analyzed (65% women), the median age was 72 years (interquartile range: 66-82). Pre-frailty and frailty were presented in 66.7% and 28.9% of them respectively. Weakness was the most frequent item (84.6%). There was a significant relationship between frailty and oral hypofunction in women. In the overall sample, the frequency of frailty was 2.06 times higher (95% CI 1.30-3.29) in patients with oral hypofunction, and this association was maintained in women (ORa: 2.18; 95% CI 1.21-3.94). Reduced occlusal force and decreased swallowing function were items significantly associated with the presence of frailty (ORa: 1.95; 95% CI 1.18-3.22 and ORa: 2.11; 95% CI 1.39-3.19, respectively). CONCLUSION: The prevalence of frailty and pre-frailty was high among institutionalized older people and was associated with the presence of hypofunction, especially in women. Decreased swallowing function was the most strongly item associated with frailty.

Mediterranean diet and risk of breast cancer: An umbrella review.

BACKGROUND: The Mediterranean Diet (MedDiet) is a healthy dietary pattern which has been related to a lower risk of certain chronic diseases, such as some cancers. However, its role in breast cancer development remains unclear. This umbrella review aims to summarize the highest available evidence on MedDiet and breast cancer risk. METHODS: Pubmed, Web of Science, and Scopus electronic platforms were searched for relevant systematic reviews and meta-analyses. The selection criteria included systematic reviews with or without meta-analysis including women aged 18 years or older which evaluated the adherence to a MedDiet as the exposure and incidence of breast cancer as the outcome variable. Overlapping and quality of the reviews using AMSTAR-2 tool were independently assessed by two authors. RESULTS: Five systematic reviews and six systematic reviews with meta-analysis were included. Overall, 4 systematic reviews - two with and two without meta-analysis - were rated as of high quality. An inverse association was found in 5 of the 9 reviews which evaluated the role of MedDiet on the risk of total breast cancer. The meta-analyses showed moderate-high heterogeneity. The risk reduction seemed to be more consistent among postmenopausal women. No association was found for MedDiet among premenopausal women. CONCLUSIONS: The results of this umbrella review suggest that adherence to a MedDiet pattern had a protective effect on the risk of breast cancer, especially for postmenopausal breast cancer. The stratification of breast cancer cases and conducting high-quality reviews are aspects needed to overcome the current results' heterogeneity and to improve knowledge in this field.

Associations of circulating levels of phthalate metabolites with cytokines and acute phase reactants in a Spanish human cohort.

The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45-1.88) and mono-iso-butyl phthalate (3.07, 2.39-3.95), mono-ethyl phthalate (2.05, 1.62-2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1ß, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1ß. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies.

Health-related quality of life in patients newly diagnosed with prostate cancer: CAPLIFE study.

PURPOSE: To analyse the Health-Related Quality of Life (HRQoL) at diagnosis of patients with prostate cancer (PCa) according to tumour extension and urinary symptomatology and to explore factors associated with HRQoL. METHODS: 408 Controls and 463 PCa cases were included. Eligibility criteria were a new diagnosis of PCa (cases), 40-80 years of age, and residence in the participating hospitals' coverage area for ≥ 6 months before recruitment. HRQoL was evaluated using the 12-Item Short-Form Health Survey, Mental (MCS) and Physical Component Summaries (PCS), and urinary symptoms with the International Prostate Symptom Score. HRQoL scores for all PCa cases, according to tumour extension and urinary symptoms, were compared with controls. In addition, information about lifestyles and comorbidities was collected and its association with low HRQoL (lower scores) were explored using logistic regression models. RESULTS: Overall cases had similar PCS score, but lower MCS score than controls. The lowest standardised scores for both PCS and MCS were reached by cases with severe urinary symptoms and a metastatic tumour [mean (SD); PCS: 41.9 (11.5), MCS: 42.3 (10.3)]. Having "below" PCS and MCS scores was associated with the presence of three or more comorbidities in the cases [aOR = 2.86 (1.19-6.84) for PCS and aOR = 3.58 (1.37-9.31) for MCS] and with severe urinary symptomatology [aOR = 4.71 (1.84-12.08) for PCS and aOR = 7.63 (2.70-21.58) for MCS]. CONCLUSION: The mental dimension of HRQoL at diagnosis of patients with PCa was lower than in controls, especially for cases with severe urinary symptoms and a metastatic tumour. Comorbidities and urinary symptoms were variables associated with the HRQoL of PCa cases.

Duration of the patient interval in breast cancer and factors associated with longer delays in low-and middle-income countries: A systematic review with meta-analysis.

OBJECTIVE: Breast cancer survival is lower in low- and middle-income countries (LMICs) partially due to many women being diagnosed with late-stage disease. The patient interval refers to the time elapsed between the detection of symptoms and the first consultation with a healthcare provider and is considered one of the core indicators for early diagnosis and treatment. The goal of the current research was to conduct a meta-analysis of the duration of the patient interval in LMICs and investigate the socio-demographic and socio-cultural factors related to longer delays in presentation. METHODS: We conducted a systematic review with meta-analysis (pre-registered protocol CRD42020200752). We searched seven information sources (2009-2022) and included 50 articles reporting the duration of patient intervals for 18,014 breast cancer patients residing in LMICs. RESULTS: The longest patient intervals were reported in studies from the Middle East (3-4 months), followed by South-East Asia (2 months), Africa (1-2 months), Latin America (1 month), and Eastern Europe (1 month). Older age, not being married, lower socio-economic status, illiteracy, low knowledge about cancer, disregarding symptoms or not attributing them to cancer, fear, negative beliefs about cancer, and low social support were related to longer delays across most regions. Longer delays were also related to use of alternative medicine in the Middle East, South-East Asia, and Africa and distrust in the healthcare system in Eastern Europe. CONCLUSIONS: There is large variation in the duration of patient intervals across LMICs in different geographical regions. Patient intervals should be reduced and, for this purpose, it is important to explore their determinants taking into account the social, cultural, and economic context.

Psychological Impact of COVID-19 in the Setting of Dentistry: A Review Article.

The worldwide pandemic has exposed healthcare professionals to a high risk of infection, exacerbating the situation of uncertainty caused by COVID-19. The objective of this review was to evaluate the psychological impact of the COVID-19 pandemic on dental professionals and their patients. A literature review was conducted using Medline-Pubmed, Web of Science, and Scopus databases, excluding systematic reviews, narratives, meta-analyses, case reports, book chapters, short communications, and congress papers. A modified version of the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the selected studies. The search retrieved 3879 articles, and 123 of these were selected for the review (7 longitudinal and 116 cross-sectional studies). Elevated anxiety levels were observed in dental professionals, especially in younger and female professionals. Except for orthodontic treatments, patients reported a high level of fear that reduced their demand for dentist treatment to emergency cases alone. The results suggest that the COVID-19 pandemic has had psychological and emotional consequences for dental professionals and their patients. Further research is necessary to evaluate the persistence of this problem over time.

Factors associated with the development of second primary tumours in head and neck cancer patients.

INTRODUCTION: The development of second primary tumours (SPTs) is one of the main causes of low survival in patients with head and neck cancer (HNC). The aim of this study was to review the evidence about factors associated with developing SPTs in patients with HNC. METHODS: An updated systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and the search was performed in Pubmed and Scopus. Only original articles with a cohort or case-control design were included. Article quality was assessed with the Newcastle-Ottawa scale. RESULTS: Thirty-six and two case-control studies were included, with quality medium (n = 5) to high (n = 33). Tobacco showed a significant association with SPT development, with risks ranging from 1.41 (95%CI: 1.04-1.91) to 5.52 (95%CI: 2.91-10.49). Regarding alcohol, risks ranged from 1.46 (95%CI: 1.12-1.91) to 21.3 (95%CI: 2.9-156). Location of the index tumour in the hypopharynx/oropharynx, absence of human papillomavirus and presence of a premalignant lesion also increased the risk of SPTs. More controversy was found for sex, age and other clinical factors of the tumour. CONCLUSION: Toxic lifestyle habits and clinical factors were associated with the risk of SPTs in HNC patients. These findings may improve individualised prevention strategies in its follow-up.

Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial.

BACKGROUND: Men with obesity tend to be insulin resistant and often have low-normal testosterone concentrations. We conducted a clinical trial aimed to evaluate potential therapeutic strategies for low testosterone in men with obesity. METHODS: We did a 1-year, parallel, randomized, double-blind, placebo-controlled trial, where we evaluated the independent and combined effects of metformin and testosterone in 106 men with obesity, aged 18-50 years, who had low levels of testosterone and no diabetes mellitus. The primary outcome was change in insulin resistance, measured as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index. Secondary outcomes included changes in total and free serum testosterone, body composition, metabolic variables, erectile function, and health-related quality of life (HRQoL). RESULTS: In the intention-to-treat analysis, the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin -2.4, 95 % CI -4.1 to -0.8, p = 0.004; testosterone -2.7, 95 % CI -4.3 to -1.1, p = 0.001; combination -3.4, 95 % CI -5.0 to -1.8, p < 0.001). Combination therapy was not superior to testosterone alone in decreasing insulin resistance (-0.7, 95 % CI -2.3 to 0.9, p = 0.383). Only the combination of metformin plus testosterone significantly increased total and free testosterone concentrations, compared to placebo. No significant changes in body composition (except for a higher decrease in fat mass in the metformin and combination group), metabolic variables, erectile function, or HRQoL were found with any treatment. CONCLUSIONS: Among men with obesity and low testosterone concentrations, the combination of metformin plus testosterone, metformin only, and testosterone only, compared to placebo, reduced insulin resistance with no evidence of additive benefit.

Public healthcare costs associated with long-term exposure to mixtures of persistent organic pollutants in two areas of Southern Spain: A longitudinal analysis.

BACKGROUND: Polychlorinated biphenyls and organochlorine pesticides are persistent organic pollutants (POPs) that had been banned or restricted in many countries, including Spain. However, their ubiquity still poses environmental and human health threats. OBJECTIVE: To longitudinally explore public healthcare costs associated with long-term exposure to a mixture of 8 POPs in a cohort of residents of two areas of Granada Province, Southern Spain. METHODS: Longitudinal study in a subsample (n = 385) of GraMo adult cohort. Exposure assessment was performed by analyzing adipose tissue POP concentrations at recruitment. Average primary care (APC) and average hospital care (AHC) expenditures of each participant over 14 years were estimated using the data from their medical records. Data analyses were performed by robust MM regression, weighted quantile sum regression (WQS) and G-computation analysis. RESULTS: In the adjusted robust MM models for APC, most POPs showed positive beta coefficients, being Hexachlorobenzene (HCB) significantly associated (ß: 1.87; 95% Confidence interval (95%CI): 0.17, 3.57). The magnitude of this association increased (ß: 3.72; 95%CI: 0.80, 6.64) when the analyses were restricted to semi-rural residents, where ß-HCH was also marginally-significantly associated to APC (ß: 3.40; 95%CI: -0.10, 6.90). WQS revealed a positive but non-significant mixture association with APC (ß: 0.14; 95%CI: -0.06, 0.34), mainly accounted for by ß-HCH (54%) and HCB (43%), that was borderline-significant in the semi-rural residents (ß: 0.23; 95%CI: -0.01, 0.48). No significant results were observed in G-Computation analyses. CONCLUSION: Long-term exposure to POP mixtures might represent a modifiable factor increasing healthcare costs, thus affecting the efficiency of the healthcare systems. However, and owing the complexity of the potential causal pathways and the limitations of the present study, further research is warranted to fully elucidate ascertain whether interventions to reduce human exposure should be considered in healthcare policies.

Dietary inflammatory index and prostate cancer risk: MCC-Spain study.

BACKGROUND: The etiology of prostate cancer (PCa) is not well-known, and the role of diet is not well established. We aimed to evaluate the role of the inflammatory power of the diet, measured by the Dietary Inflammatory Index (DII®), on the risk of PCa. METHODOLOGY: A population-based multicase-control (MCC-Spain) study was conducted. Information was collected on sociodemographic characteristics, personal and family antecedents, and lifestyles, including diet from a Food Frequency Questionnaire. The inflammatory potential of the diet was assessed using the energy-adjusted Dietary Inflammatory Index (E-DII) based on 30 parameters (a higher score indicates a higher inflammatory capacity of the diet). Tertiles of E-DII were created using the cut-off points from the control group. The International Society of Urology Pathology (ISUP) was grouped as ISUP 1, ISUP 2, or ISUP 3-5. Unconditional logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association between E-DII score and PCa risk. RESULTS: A total of 928 PCa cases and 1278 population controls were included. Among PCa cases, the mean value of the E-DII score was 0.18 (SD: 1.9) vs. 0.07 (SD: 1.9) in the control group (p = 0.162). Cases with a more pro-inflammatory diet (3rd tertile) had the highest risk of PCa, aORT3vsT1 = 1.30 (95% CI 1.03-1.65) (p-trend = 0.026). When stratifying by ISUP, this risk association was observed only for ISUP 2 and ISUP 3-5, aORT3vsT1 = 1.46 (95% CI 1.02-2.10) and 1.60 (95% CI 1.10-2.34), respectively. CONCLUSION: A positive association was observed between consuming a pro-inflammatory diet and PCa in the MCC-Spain population, specifically for an ISUP grade greater or equal than 2.

Differential Bioaccumulation Patterns of α, ß-Hexachlorobenzene and Dicofol in Adipose Tissue from the GraMo Cohort (Southern Spain).

To identify bioaccumulation patterns of α-, ß- hexachlorocyclohexane (HCH) and dicofol in relation to sociodemographic, dietary, and lifestyle factors, adipose tissue samples of 387 subjects from GraMo cohort in Southern Spain were analyzed. Potential predictors of these organochlorine pesticides (OCP) levels were collected by face-to-face interviews and assessed by multivariable linear and logistic regression. OCPs were detected in 84.2% (ß-HCH), 21.7% (α-HCH), and 19.6% (dicofol) of the population. ß-HCH levels were positively related to age, body mass index (BMI), mother's occupation in agriculture during pregnancy, living in Poniente and Alpujarras, white fish, milk and water consumption, and negatively related to being male, living near to an agricultural area, working ≥10 years in agriculture, and beer consumption. Detectable α-HCH levels were positively related to age, BMI, milk consumption, mother's occupation in agriculture during pregnancy, and negatively with residence in Poniente and Alpujarras, Granada city, and Granada Metropolitan Area. Residence near to an agricultural area, smoking habit, white fish and water consumption, and living in Poniente and Alpujarras, Granada city and Granada Metropolitan Area were negatively associated with detectable dicofol levels. Our study revealed different bioaccumulation patterns of α, ß-HCH and dicofol, probably due to their dissimilar period of use, and emphasize the need for assessing the exposure to frequently overlooked pollutants.

Identification of novel prostate cancer genes in patients stratified by Gleason classification: Role of antitumoral genes.

Prostate cancer (PCa) is a tumor with a great heterogeneity, both at a molecular and clinical level. Despite its global good prognosis, cases can vary from indolent to lethal metastatic and scientific efforts are aimed to discern those with worse outcomes. Current prognostic markers, as Gleason score, fall short when it comes to distinguishing these cases. Identification of new early biomarkers to enable a better PCa distinction and classification remains a challenge. In order to identify new genes implicated in PCa progression we conducted several differential gene expression analyses over paired samples comparing primary PCa tissue against healthy prostatic tissue of PCa patients. The results obtained show that this approach is a serious alternative to overcome patient heterogeneity. We were able to identify 250 genes whose expression varies along with tissue differentiation-healthy to tumor tissue, 161 of these genes are described here for the first time to be related to PCa. The further manual curation of these genes allowed to annotate 39 genes with antitumoral activity, 22 of them described for the first time to be related to PCa proliferation and metastasis. These findings could be replicated in different cohorts for most genes. Results obtained considering paired differential expression, functional annotation and replication results point to: CGREF1, UNC5A, C16orf74, LGR6, IGSF1, QPRT and CA14 as possible new early markers in PCa. These genes may prevent the progression of the disease and their expression should be studied in patients with different outcomes.

Determinants of masticatory performance assessed by mixing ability tests.

STATEMENT OF PROBLEM: Studies determining the main predictors of masticatory performance by using mixing ability tests are sparse. PURPOSE: The purpose of this clinical study was to identify potential determinants of masticatory performance assessed by analyzing a patient's masticatory ability using bicolored chewing gum and visual, quantitative, and interactive methods. MATERIAL AND METHODS: Nondental participants attending healthcare centers were consecutively recruited in Granada, Spain. The inclusion criteria were older than18 years and resident in the coverage area of the reference healthcare centers for at least the previous 6 months. The participants were excluded if they had received dental treatment in the previous 6 months or they were unable to communicate. The masticatory performance was determined by using 2-colored chewing gum (Kiss 3 white and blue; Smint) that was masticated for a total of 20 strokes. The masticated gum was crushed between 2 transparent glass slides, creating a 1-mm-thick specimen that was subsequently scanned. The mixed-color area was calculated as a percentage by using Photoshop as described by Schimmel et al and designated as the standard method. In addition, all images made were analyzed by using the Web application the Chewing Performance Calculator. In addition, the masticated bolus was inspected visually, and mastication performance was classified as being poor, moderate, or good. Sociodemographic data, as well as data on behaviors, medical and nutritional status, health-related quality of life, saliva, and general oral health, were collected for all participants to identify the main determinants of masticatory performance. RESULTS: One hundred thirty-seven participants were enrolled. The masticatory performance values obtained using both methods (standard method and Chewing Performance Calculator) were significantly greater for well masticated gum (P<.001), which had been visually classified as being poorly masticated (69.1% for standard method and 43.5% for Chewing Performance Calculator), moderately masticated (89.7% for standard method and 67.3% for Chewing Performance Calculator), and well masticated (97.3% for standard method and 80.3% for Chewing Performance Calculator). The bivariate analyses revealed that masticatory performance was significantly higher in younger people (<65 years) (P=.008), who also had a higher basal salivary flow rate (P<.001), were nondenture users (P=.002), and had more standing teeth and occlusal units (P<.001). However, the multiple regression analyses showed that the number of occlusal units was the only significant predictor of masticatory performance. In addition, the mean masticatory performance (95% confidence interval: 47.7% to 56.8%) was found to be greatly improved (by 1.2% to 2.2%), with each occlusal unit, in accordance with the Chewing Performance Calculator and between 0.8% and 1.8% according to the standard method; the basal masticatory performance was calculated as 72.1% to 81.2% (95% confidence interval). CONCLUSIONS: The number of occlusal units is one of the main predictors of masticatory performance when a 2-color bolus is used to test mixing ability.

Prostate cancer genetic propensity risk score may modify the association between this tumour and type 2 diabetes mellitus (MCC-Spain study).

BACKGROUND: Some studies have reported an inverse association between type 2 diabetes mellitus (T2DM) and prostate cancer (PCa), but results on this issue are still inconsistent. In this study, we evaluate whether this heterogeneity might be related to differences in this relationship by tumour or by individual genetic susceptibility to PCa. METHODS: We studied 1047 incident PCa cases and 1379 randomly selected controls, recruited in 7 Spanish provinces for the population-based MCC-Spain case-control. Tumour were classified by aggressiveness according to the International Society of Urological Pathology (ISUP), and we constructed a PCa polygenic risk score (PRS) as proxy for genetic susceptibility. The epidemiological questionnaire collected detailed self-reported data on T2DM diagnosis and treatment. The association between T2DM status and PCa was studied by fitting mixed logistic regression models, and, for its association by aggressiveness of PCa, with multinomial logistic regression models. To evaluate the possible modulator role of PRS in this relationship, we included the corresponding interaction term in the model, and repeated the analysis stratified by PRS tertiles. RESULTS: Globally, our results showed an inverse association between T2DM and overall PCa limited to grade 1 tumours (ORISUP = 1: 0.72; 95% CI: 0.53-0.98), which could be compatible with a detection bias. However, PCa risk also varied with duration of diabetes treatment -inversely to metformin and positively with insulin-, without differences by aggressiveness. When we considered genetic susceptibility, T2DM was more strongly associated with lower PCa risk in those with lower PRS (ORtertile 1: 0.31; 95% CI: 0.11-0.87), independently of ISUP grade. CONCLUSIONS: Our findings reinforce the need to include aggressiveness and susceptibility of PCa, and T2DM treatments in the study of the relationship between both diseases.