ABSTRACT
Curcumin and omega-3 polyunsaturated fatty acids (ω-3 PUFA) are multifunctional compounds which play an important role in Alzheimer's disease (AD) and little has been addressed about the role of these two compounds together in the progression of the disease. There is evidence of the beneficial effect of combined administration of ω-3 PUFA and other dietary supplements such as vitamins and polyphenols in the prevention of AD, although much remains to be understood about their possible complementary or synergistic activity. Therefore, the objective of this work is to review the research focused on studying the effect and mechanisms of action of curcumin, ω-3 PUFA, and the combination of these nutraceutical compounds, particularly on AD, and to integrate the possible ways in which these compounds can potentiate their effect. The most important pathophysiologies that manifest in AD will be addressed, in order to have a better understanding of the mechanisms of action through which these bioactive compounds exert a neuroprotective effect.
Subject(s)
Alzheimer Disease , Curcumin , Dietary Supplements , Fatty Acids, Omega-3 , Neuroprotective Agents , Curcumin/therapeutic use , Curcumin/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Humans , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Drug SynergismABSTRACT
IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate. OBJECTIVE: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP. DESIGN, SETTING AND PARTICIPANTS: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres. EXPOSURES: Participants self-administered 350 mg of erlotinib by mouth, one time per week for 6 months. MAIN OUTCOMES AND MEASURES: Duodenal polyp burden (sum of polyp diameters) was assessed in the proximal duodenum by esophagogastroduodenoscopy performed at baseline and 6 months, with mean per cent change defined as the primary efficacy outcome of interest. Rate of grade 2-3 AEs was evaluated as a co-primary outcome. Secondary outcomes included changes in total duodenal polyp count, along with changes in lower gastrointestinal (GI) polyp burden and count (for participants examined by optional lower endoscopy). RESULTS: Forty-six participants (mean age, 44.1 years (range, 18-68); women, 22 (48%)) were enrolled; 42 participants completed 6 months of intervention and were included in the per-protocol analysis. Duodenal polyp burden was significantly reduced after 6 months of weekly erlotinib intervention, with a mean per cent change of -29.6% (95% CI, -39.6% to -19.7%; p<0.0001). Similar results were observed in subgroup analyses defined by participants with advanced duodenal polyposis (Spigelman 3) at baseline (mean, -27%; 95% CI, -38.7% to -15.2%; p<0.0001). Post-intervention Spigelman stage was downstaged in 12% of the participants. Lower GI polyp number was also decreased after 6 months of intervention (median, -30.8%; IQR, -47.4% to 0.0%; p=0.0256). Grade 2 or 3 AEs were reported in 71.7% of subjects, with only two experiencing grade 3 toxicity at least possibly related to intervention. CONCLUSION: In this single-arm, multi-centre trial of participants with FAP, erlotinib one time per week resulted in markedly lower duodenal polyp burden, and modestly reduced lower GI polyp burden, after 6 months of intervention. While AEs were still reported by nearly three-quarters of all participants, these events were generally lower grade and well-tolerated. These findings support further investigation of erlotinib as an effective, acceptable cancer preventive agent for FAP-associated GI polyposis. TRIAL REGISTRATION NUMBER: NCT02961374.
Subject(s)
Adenomatous Polyposis Coli , Duodenal Neoplasms , Humans , Female , Adult , Erlotinib Hydrochloride/adverse effects , Adenomatous Polyposis Coli/drug therapy , Duodenal Neoplasms/drug therapy , Duodenum , Endoscopy, GastrointestinalABSTRACT
Cytomegalovirus infection occurs commonly during infancy. Postnatal infection in term infants is usually asymptomatic; however, infection in preterm infants can be associated with clinical manifestations during the neonatal period. Nevertheless, few studies to assess the frequency of cytomegalovirus infection in preterm infants have been performed outside of high-income countries. We analyzed the incidence of congenital and postnatal cytomegalovirus infection in a cohort of preterm infants. Cytomegalovirus infection was detected during the neonatal period in four of 178 infants; in three of them, the virus was detected during the first 3 weeks of life and, therefore, congenital infection was confirmed (1.7% incidence). Postnatal infection was detected in 44 (36.4%) of 121 infants who were assessed after discharge from the neonatal intensive care unit. Cytomegalovirus infection was significantly associated with the duration of breastfeeding. In addition, we characterized cytomegalovirus strains detected in infants together with sequences available at GenBank, based on sequences of the UL18 gene. Cytomegalovirus UL18-sequences clustered in five distinct clades (A-E), and sequences obtained from infants in our study were distributed in four of the five clades; 44.4% of these sequences were included in clade E. Breastfeeding duration was shorter on average (5.6 months) in infants with sequences in clade E compared to infants with sequences in the other three clades (8.2 months; p = .07). In conclusion, we provide information regarding the high incidence of cytomegalovirus infection in preterm infants. Further studies are warranted to assess if cytomegalovirus strain characteristics are associated with the risk of infection acquisition during infancy.
Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Breast Feeding , Cytomegalovirus/genetics , Female , Humans , Incidence , Infant , Infant, Newborn , Infant, Premature , Milk, HumanABSTRACT
Photosynthesis is a vital process for the planet. Its estimation involves the measurement of different variables and its processing through a mathematical model. This article presents a black-box mathematical model to estimate the net photosynthesis and its digital implementation. The model uses variables such as: leaf temperature, relative leaf humidity, and incident radiation. The model was elaborated with obtained data from Capsicum annuum L. plants and calibrated using genetic algorithms. The model was validated with Capsicum annuum L. and Capsicum chinense Jacq. plants, achieving average errors of 3% in Capsicum annuum L. and 18.4% in Capsicum chinense Jacq. The error in Capsicum chinense Jacq. was due to the different experimental conditions. According to evaluation, all correlation coefficients (Rho) are greater than 0.98, resulting from the comparison with the LI-COR Li-6800 equipment. The digital implementation consists of an FPGA for data acquisition and processing, as well as a Raspberry Pi for IoT and in situ interfaces; thus, generating a useful net photosynthesis device with non-invasive sensors. This proposal presents an innovative, portable, and low-scale way to estimate the photosynthetic process in vivo, in situ, and in vitro, using non-invasive techniques.
Subject(s)
Capsicum , Models, Theoretical , Photosynthesis , Plant LeavesABSTRACT
Platelet concentrates (PCs) obtained from whole blood are produced by fractionation of the buffy coat (BC) or the platelet-rich plasma. Despite the improvements in the technologies used for the hemocomponent fractionation, the proportion of PCs that do not accomplish the quality requirements is high. This study aimed to determine whether the basal platelet and leukocyte counts are predictive factors of the quality of the PCs obtained from BC by semiautomated fractionation. Quality control registers of 196 PCs were analyzed. Gender- and age-dependence of the blood cell count and the characteristics of PCs were evaluated. Platelet yield and residual leukocytes in the PCs were correlated with the platelet and leukocyte counts and the age of the donors. Predictive efficacy was assessed, and an optimal cut-off was established. The proportions of PCs accepted and rejected by using or not the optimal cut-off were compared. 50.0% of the PCs accomplished all the quality control requirements. Female donors had a higher basal platelet count than males. A correlation was observed between basal platelets and platelet yield, but not between basal leukocytes and residual leukocytes. The basal platelet count predicted the quality of the PCs. A cut-off of 231,000 platelets/mm3 was established, but it did not improve the proportion of accepted PCs. In conclusion, we found that the basal platelet count is correlated with the platelet yield. The basal leukocyte count is not correlated with the residual leukocytes. The established cut-off for the basal platelet count did not improve the proportion of accepted PCs.
Subject(s)
Blood Platelets/metabolism , Blood Preservation/methods , Leukocyte Count/methods , Platelet Count/methods , Female , Humans , MaleABSTRACT
INTRODUCTION: Algorithms have been developed to predict the platelet yield after apheresis from the donor's data, as well as the effect on the blood cell count, to extract an acceptable platelet number without affecting the donor. However, the evaluation of these algorithms has not been widely reported. This study aimed to assess the accuracy of the predictive algorithms of the Trima Accel v. 6 blood collection system. METHODS: Platelet concentrates (PCs) obtained by apheresis were analyzed. Platelet count and hematocrit were compared pre- and post-apheresis. Calculated post-apheresis platelet count (CPAPC), hematocrit (CPAH), and platelet yield (CPY), and their actual values were correlated. The bias of the algorithms was assessed with Bland-Altman plots, and the prediction of the extraction of single or double platelet products was evaluated. RESULTS: Two hundred and seventy-nine PCs were analyzed. Post-apheresis platelet count (PAPC) and hematocrit were decreased. A moderate correlation was observed between CPY and the actual yield, with a negative bias, and a trend to increase alongside the magnitude of the measurements. CPAPC and CPAH were strongly correlated with their actual values without bias. Prediction of single or double platelet product extraction showed a significant agreement with the actual outcomes. CONCLUSIONS: The predictive algorithm for the platelet yield showed bias, and a trend to underestimate the actual platelet yields when they are higher. The algorithms for the prediction of the PAPC and hematocrit did not show bias, proving their accuracy. Prediction of a single or double platelet product extraction has a strong agreement with the APY.
Subject(s)
Plateletpheresis/methods , Adult , Algorithms , Female , Humans , Male , Platelet Count , SoftwareABSTRACT
OBJECTIVE: To determine the representation of Black/AA women surgeons in academic medicine among U.S. medical school faculty and to assess the number of NIH grants awarded to Black/AA women surgeon-scientists over the past 2 decades. SUMMARY OF BACKGROUND DATA: Despite increasing ethnic/racial and sex diversity in U.S. medical schools and residencies, Black/AA women have historically been underrepresented in academic surgery. METHODS: A retrospective review of the Association of American Medical Colleges 2017 Faculty Roster was performed and the number of grants awarded to surgeons from the NIH (1998-2017) was obtained. Data from the Association of American Medical Colleges included the total number of medical school surgery faculty, academic rank, tenure status, and department Chair roles. Descriptive statistics were performed. RESULTS: Of the 15,671 U.S. medical school surgical faculty, 123 (0.79%) were Black/AA women surgeons with only 11 (0.54%) being tenured faculty. When stratified by academic rank, 15 (12%) Black/AA women surgeons were instructors, 73 (59%) were assistant professors, 19 (15%) were associate professors, and 10 (8%) were full professors of surgery. Of the 372 U.S. department Chairs of surgery, none were Black/AA women. Of the 9139 NIH grants awarded to academic surgeons from 1998 and 2017, 31 (0.34%) grants were awarded to fewer than 12 Black/AA women surgeons. CONCLUSION: A significant disparity in the number of Black/AA women in academic surgery exists with few attaining promotion to the rank of professor with tenure and none ascending to the role of department Chair of surgery. Identifying and removing structural barriers to promotion, NIH grant funding, and academic advancement of Black/AA women as leaders and surgeon-scientists is needed.
Subject(s)
Black or African American , Faculty, Medical/supply & distribution , Physicians, Women/supply & distribution , Research Support as Topic , Surgeons/supply & distribution , Adult , Female , Humans , Retrospective Studies , Schools, Medical , United StatesABSTRACT
Transforming growth factor ß (TGF-ß) has been shown to play a role in immunity against different pathogens in vitro and against parasites in vivo However, its role in viral infections in vivo is incompletely understood. Using a neonatal mouse model of heterologous rhesus rotavirus (RV) vaccination, we show that the vaccine induced rotavirus-specific CD4 T cells, the majority of which lacked expression of KLRG1 or CD127, and a few regulatory rotavirus-specific CD4 T cells that expressed surface latency-associated peptide (LAP)-TGF-ß. In these mice, inhibiting TGF-ß, with both a neutralizing antibody and an inhibitor of TGF-ß receptor signaling (activin receptor-like kinase 5 inhibitor [ALK5i]), did not change the development or intensity of the mild diarrhea induced by the vaccine, the rotavirus-specific T cell response, or protection against a subsequent challenge with a murine EC-rotavirus. However, mice treated with anti-LAP antibodies had improved protection after a homologous EC-rotavirus challenge, compared with control rhesus rotavirus-immunized mice. Thus, oral vaccination with a heterologous rotavirus stimulates regulatory RV-specific CD4 LAP-positive (LAP+) T cells, and depletion of LAP+ cells increases vaccine-induced protection.IMPORTANCE Despite the introduction of several live attenuated animal and human rotaviruses as efficient oral vaccines, rotaviruses continue to be the leading etiological agent for diarrhea mortality among children under 5 years of age worldwide. Improvement of these vaccines has been partially delayed because immunity to rotaviruses is incompletely understood. In the intestine (where rotavirus replicates), regulatory T cells that express latency-associated peptide (LAP) play a prominent role, which has been explored for many diseases but not specifically for infectious agents. In this paper, we show that neonatal mice given a live oral rotavirus vaccine develop rotavirus-specific LAP+ T cells and that depletion of these cells improves the efficiency of the vaccine. These findings may prove useful for the design of strategies to improve rotavirus vaccines.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Rotavirus Infections/prevention & control , Rotavirus Vaccines/immunology , T-Lymphocyte Subsets/immunology , Transforming Growth Factor beta/analysis , Administration, Oral , Animals , Animals, Newborn , CD4-Positive T-Lymphocytes/chemistry , Diarrhea/prevention & control , Disease Models, Animal , Immunity, Heterologous , Mice , Rotavirus Vaccines/administration & dosage , T-Lymphocyte Subsets/chemistry , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: Familial adenomatous polyposis is an autosomal dominant disorder characterized by the development of hundreds of colorectal adenomas and eventually colorectal cancer. Oral administration of the spice curcumin has been followed by regression of polyps in patients with this disorder. We performed a double-blinded randomized trial to determine the safety and efficacy of curcumin in patients with familial adenomatous polyposis. METHODS: This study included 44 patients with familial adenomatous polyposis (18-85 years old) who had not undergone colectomy or had undergone colectomy with ileorectal anastomosis or ileal anal pouches, had at least 5 intestinal adenomatous polyps, and had enrolled in Puerto Rico or the United States from September 2011 through November 2016. Patients were randomly assigned (1:1) to groups given 100% pure curcumin (1,500 mg orally, twice per day) or identical-appearing placebo capsules for 12 months. The number and size of lower gastrointestinal tract polyps were evaluated every 4 months for 1 year. The primary outcome was the number of polyps in the curcumin and placebo groups at 12 months or at the time of withdrawal from the study according to the intention-to-treat principle. RESULTS: After 1 year of treatment, the average rate of compliance was 83% in the curcumin group and 91% in the placebo group. After 12 weeks, there was no significant difference in the mean number of polyps between the placebo group (18.6; 95% CI, 9.3-27.8) and the curcumin group (22.6; 95% CI, 12.1-33.1; P = .58). We found no significant difference in mean polyp size between the curcumin group (2.3 mm; 95% CI, 1.8-2.8) and the placebo group (2.1 mm; 95% CI, 1.5-2.7; P = .76). Adverse events were few, with no significant differences between groups. CONCLUSIONS: In a double-blinded randomized trial of patients with familial adenomatous polyposis, we found no difference in the mean number or size of lower intestinal tract adenomas between patients given curcumin 3,000 mg/day and those given placebo for 12 weeks. Clinicaltrials.gov ID NCT00641147.
Subject(s)
Adenoma/drug therapy , Adenomatous Polyposis Coli/drug therapy , Antineoplastic Agents/administration & dosage , Colorectal Neoplasms/drug therapy , Curcumin/administration & dosage , Adenoma/etiology , Adenomatous Polyposis Coli/complications , Adolescent , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/etiology , Double-Blind Method , Female , Humans , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
The superoxide dismutase type 1 (SOD1) gene is the first responsible gene mapped in amyotrophic lateral sclerosis type 1 (ALS1), and it codes for the enzyme SOD1, the function of which is to protect against damage mediated by free radicals deriving from oxygen. Its pathophysiological mechanism in ALS1 is related to ischemia. Several molecular studies of the SOD1 gene show that point mutations are the most frequent. The most common mutations in familial cases are p.A4V, p.I113Y, p.G37R, p.D90A and p.E100G, which account for more than 80% of cases, although intronic mutations have also been described as responsible for ALS1. Sporadic cases are explained by mutations in other genes such as SETX and C9orf72. ALS1 is a complex disease with genetic heterogeneity. On the other hand, familial and sporadic cases have a different etiology, which is explained by molecular heterogeneity and multiple pathogenic mechanisms that lead to ALS1; oxidative stress and ischemia are not the only cause. In Mexico, ALS molecular genetics studies are scarce. Clinical studies show an increase in cytokines such as adipsin in cerebrospinal fluid.
El gen SOD1 es el primer gen responsable mapeado en la esclerosis lateral amiotrófica tipo 1 (ELA1) y codifica para la enzima superóxido dismutasa tipo 1 (SOD1), cuya función es proteger del daño mediado de los radicales libres derivados del oxígeno; su mecanismo fisiopatológico en ELA1 se relaciona con isquemia. Diversos estudios moleculares del gen SOD1 muestran que las mutaciones puntuales son las más frecuentes. Las mutaciones más comunes en los casos familiares son p.A4V, p.I113Y, p.G37R, p.D90A y p.E100G, que explican más de 80 % de los casos, aunque también se han descrito mutaciones intrónicas como responsables de esclerosis lateral amiotrófica tipo 1. Los casos esporádicos se explican por mutaciones en otros genes como SETX y C9orf72. ELA1 es una enfermedad compleja con heterogeneidad genética. Por otra parte, los casos familiares y esporádicos tienen etiología distinta, lo cual se explica por la heterogeneidad molecular y múltiples mecanismos patogénicos que conducen a ELA1; el estrés oxidativo y la isquemia no son la única causa. En México son escasos los estudios de genética molecular de esclerosis lateral amiotrófica. Los estudios clínicos muestran incremento de citocinas como la adipsina en el líquido cefalorraquídeo.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Superoxide Dismutase-1/genetics , C9orf72 Protein/genetics , DNA Helicases/genetics , Genotype , Humans , Introns/genetics , Ischemia/complications , Multifunctional Enzymes/genetics , Phenotype , Point Mutation , RNA Helicases/genetics , Reactive Oxygen Species , Superoxide Dismutase-1/physiologyABSTRACT
The superoxide dismutase type 1 (SOD1) gene is the first responsible gene mapped in amyotrophic lateral sclerosis type 1 (ALS1), and it codes for the enzyme SOD1, the function of which is to protect against damage mediated by free radicals deriving from oxygen. Its pathophysiological mechanism in ALS1 is related to ischemia. Several molecular studies of the SOD1 gene show that point mutations are the most frequent. The most common mutations in familial cases are p.A4V, p.I113Y, p.G37R, p.D90A and p.E100G, which account for more than 80% of cases, although intronic mutations have also been described as responsible for ALS1. Sporadic cases are explained by mutations in other genes such as SETX and C9orf72. ALS1 is a complex disease with genetic heterogeneity. On the other hand, familial and sporadic cases have a different etiology, which is explained by molecular heterogeneity and multiple pathogenic mechanisms that lead to ALS1; oxidative stress and ischemia are not the only cause. In Mexico, ALS molecular genetics studies are scarce. Clinical studies show an increase in cytokines such as adipsin in cerebrospinal fluid.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Superoxide Dismutase-1/genetics , Age of Onset , Amyotrophic Lateral Sclerosis/enzymology , Humans , Ischemia/complications , Mexico , Oxidative Stress , Point MutationABSTRACT
BACKGROUND: Although there is adequate knowledge as to the role of traditional cardiovascular risk factors on stroke incidence, knowledge of other risk factors, particularly genetic ones, is still incomplete. METHODS: To assess the participation of some polymorphisms, along with other modifiable risk factors, a case-control study was conducted. A total of 253 cases were identified in the emergency room of a general regional hospital, with a clinical trait of stroke confirmed by a skull computerized axial tomography scan. In the surgery ward, 253 controls were identified, gender and age (±5 years) matched. Biochemical parameters were measured, and 4 polymorphisms were genotyped by polymerase chain reaction, rs1801133 (methylenetetrahydrofolate reductase [MTHFR]), rs1498373 (dimethylarginine dimethylaminohydrolase type 1 [DDAH1]), rs662799 (apolipoprotein A5 [APOA5]), and rs1799983 (endothelial nitric oxide). Odds ratios were estimated to assess the strength of association, with 95% confidence intervals, both in a matched case-control analysis and in a conditional regression analysis. RESULTS: Cases had higher mean blood pressure and triglycerides and lower hemoglobin levels. Heterozygous and homozygous subjects to the rs1801133 variant of the MTHFR gene had a 3-fold higher risk of stroke. In the dominant model, those with the polymorphism rs662799 of the promoter region for APOA5 had twice the risk of stroke. Anemia increased the risk of stroke 4-fold. CONCLUSIONS: Polymorphisms of the genes MTHFR (rs1801133) and APOA5 (rs662799), as well as anemia, are independent risk factors for stroke in Mexicans, together with traditional cardiovascular risk factors such as high triglycerides and high blood pressure.
Subject(s)
Anemia/blood , Apolipoprotein A-V/genetics , Brain Ischemia/blood , Brain Ischemia/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Single Nucleotide , Stroke/genetics , Anemia/diagnosis , Anemia/epidemiology , Biomarkers/blood , Blood Pressure , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Case-Control Studies , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Hemoglobins/metabolism , Heterozygote , Homozygote , Humans , Hypertension/epidemiology , Hypertension/physiopathology , Hypertriglyceridemia/blood , Hypertriglyceridemia/epidemiology , Logistic Models , Mexico/epidemiology , Multivariate Analysis , Odds Ratio , Phenotype , Prevalence , Promoter Regions, Genetic , Risk Factors , Stroke/blood , Stroke/diagnosis , Triglycerides/bloodABSTRACT
OBJECTIVE: The objective of this study was to explore the knowledge, thoughts, and beliefs regarding the Zika virus and its prevention in a community of residents in the municipality of Caguas, Puerto Rico, and elicit their concerns and perceptions of risk. METHODS: A quantitative, non experimental, descriptive, cross-sectional correlational study was conducted in a community in Caguas, Puerto Rico. A structured questionnaire was administered to a sample of 158 residents, aged 21 and older, who participated voluntarily. The data were analyzed using SPSS version 17 via univariate and bivariate analysis. RESULTS: Of 158 surveyed, 64.6% were women; with a population average of 53.85 years. Of the respondents who believed that they would be affected in some way if they were infected by the Zika virus, over half (52.3%) felt that the virus represented a significant threat to their emotional stability. Of those who perceived emotional threat, 39.5% (n=32) continued to study after completing high school (X2=9.217, p=0.027), 57.9% (n=55) had private health insurance (X2=6.325; p=0.042), and 67.9% (n=55) reported it was little or unlikely to become infected (X2= 6.783; p=0.034). Out of those concerned, 57.4% (n=54) considered Zika very or extremely severe (X2=22.827, p<0.001) and 98.9% (n=93) clean the house surroundings as a preventive measure (X2 = 4.951, p=0.026). Lack of interest was the most common reason identified for not complying with preventive actions by the residents (89.2%). CONCLUSION: The underestimation both of the risk concerning the Zika virus and of its consequences was evident. This study reaffirms the need to develop a network that effectively and constantly communicates risk estimates, doing so while addressing the specific needs within the communities served by that network. Community interventions aimed at improving the benefits of and reducing the risks associated with and the perceived barriers to preventive behaviors are needed.
Subject(s)
Emotions , Health Knowledge, Attitudes, Practice , Zika Virus Infection/epidemiology , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pilot Projects , Puerto Rico/epidemiology , Risk , Surveys and Questionnaires , Young Adult , Zika Virus Infection/prevention & control , Zika Virus Infection/psychologyABSTRACT
OBJECTIVE: A major impediment to translating chemoprevention to clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations of field carcinogenesis. We now wanted to ascertain if reversion of two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy. DESIGN: We conducted a multicentre, prospective, randomised, double-blind placebo-controlled, clinical trial in subjects with a history of colonic neoplasia who manifested altered SPEC/FRAC in histologically normal colonic mucosa. Subjects (n=79) were randomised to 325â mg aspirin or placebo. The primary endpoint changed in FRAC and SPEC spectral markers after 3â months. Mucosal levels of prostaglandin E2 (PGE2) and UDP-glucuronosyltransferase (UGT)1A6 genotypes were planned secondary endpoints. RESULTS: At 3â months, the aspirin group manifested alterations in SPEC (48.9%, p=0.055) and FRAC (55.4%, p=0.200) with the direction towards non-neoplastic status. As a measure of aspirin's pharmacological efficacy, we assessed changes in rectal PGE2 levels and noted that it correlated with SPEC and FRAC alterations (R=-0.55, p=0.01 and R=0.57, p=0.009, respectively) whereas there was no significant correlation in placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, the changes in SPEC and FRAC to a less neoplastic direction occurred only in the variant consonant with epidemiological evidence of chemoprevention. CONCLUSIONS: We provide the first proof of concept, albeit somewhat underpowered, that spectral markers reversion mirrors antineoplastic efficacy providing a potential modality for titration of agent type/dose to optimise chemopreventive strategies in clinical practice. TRIAL NUMBER: NCT00468910.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Colonic Neoplasms/prevention & control , Spectrum Analysis/methods , Aged , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/adverse effects , Biomarkers, Tumor , Chemoprevention , Dinoprostone/metabolism , Double-Blind Method , Female , Genotype , Glucuronosyltransferase/genetics , Humans , Intestinal Mucosa/metabolism , Male , Middle Aged , Prospective Studies , Rectum/metabolismABSTRACT
This cross-sectional study examined whether people who are exposed to mercury (Hg) vapours in ongoing artisanal gold mining activities have alteration in kidney function monitoring parameters. The study enrolled 164 miners and 127 participant controls. The Hg concentrations for miners and control participants were measured in blood (B-Hg; median 7.0 vs. 2.5 µg/L), urine (U-Hg; median 3.9 vs. 1.5 µg/g creatinine) and hair (H-Hg; median 0.8 vs. 0.4 µg/g hair). The biomarkers of renal function were creatinine, albumin and excretion of ß-2 microglobulin. Glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration equation. Significant statistical differences were found in Hg concentrations and eGFR levels between the two study groups ( p < 0.01) but not with the other biomarkers of renal function. A multiple regression model was applied to explore the relationship of eGFR levels and Hg concentrations. However, no association was found between the prevalence of reduced eGFR (<71.96 mL/min/1.73 m2) and the B-Hg or U-Hg levels after adjustment for covariates. Nevertheless, it was observed that having B-Hg levels above 10 µg Hg/L decreased the eGFR by 1.7 mL/min/1.73 m2 (confidence interval 95% -5.1 to 1.7) compared to having levels below 2.0 µg Hg/L. Our results found no support for kidney damage associated with Hg vapour exposure in ongoing artisanal gold mining, whose population has a level of Hg exposure from low to moderate (B-Hg from 3.4 to 11.0 µg/L and U-Hg from 1.3 to 9.6 µg/g creatinine).
Subject(s)
Kidney/drug effects , Mercury/toxicity , Mining , Occupational Exposure/adverse effects , Adult , Biomarkers/blood , Biomarkers/urine , Colombia , Cross-Sectional Studies , Environmental Monitoring , Female , Gold , Hair/chemistry , Humans , Kidney/metabolism , Kidney Diseases/chemically induced , Kidney Diseases/diagnosis , Male , Mercury/blood , Mercury/urine , Middle AgedABSTRACT
The study of metal-tolerant bacteria is important for bioremediation of contaminated environments and development of green technologies for material synthesis due to their potential to transform toxic metal ions into less toxic compounds by mechanisms such as reduction, oxidation and/or sequestration. In this study, we report the isolation of seven lead-tolerant bacteria from a metal-contaminated site at Zacatecas, México. The bacteria were identified as members of the Staphylococcus and Bacillus genera by microscopic, biochemical and 16S rDNA analyses. Minimal inhibitory concentration of these isolates was established between 4.5 and 7.0 mM of Pb(NO3)2 in solid and 1.0-4.0 mM of Pb(NO3)2 in liquid media. A quantitative analysis of the lead associated to bacterial biomass in growing cultures, revealed that the percentage of lead associated to biomass was between 1 and 37% in the PbT isolates. A mechanism of complexation/biosorption of lead ions as inorganic phosphates (lead hydroxyapatite and pyromorphite) in bacterial biomass, was determined by Fourier transform infrared spectroscopy and X-ray diffraction analyses. Thus, the ability of the lead-tolerant isolates to transform lead ions into stable and highly insoluble lead minerals make them potentially useful for immobilization of lead in mining waste.
Subject(s)
Bacteria/metabolism , Immobilization , Lead/metabolism , Siderophores/metabolism , Bacillus/isolation & purification , Bacillus/metabolism , Bacteria/classification , Bacteria/growth & development , Bacteria/isolation & purification , Biodegradation, Environmental , Biomass , Culture Media/chemistry , Lead/pharmacology , Mexico , Minerals/metabolism , Mining , Nitrates/pharmacology , Phosphates/metabolism , Soil Pollutants/metabolism , Spectroscopy, Fourier Transform Infrared , Staphylococcus/isolation & purification , Staphylococcus/metabolism , Wastewater , X-Ray DiffractionABSTRACT
BACKGROUND: Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism and its polymorphisms are possibly implicated in the etiology of ischemic cerebrovascular disease (CVD). The aim of this work was to determine the association of the of D9N, N291S, and T495G polymorphisms of the LPL gene as a risk factor for the development of CVD. METHODS: A case-control study was conducted that included 100 patients with CVD and 120 healthy controls. All the subjects were genotyped for the D9N, N291S, and T495G polymorphisms of the LPL gene through polymerase chain reaction-restriction fragment length polymorphism, and the results were analyzed for their association with CVD. RESULTS: The D9N genotype was not significantly correlated with CVD; the odds ratio (OR) between the control subjects and CVD patients was .29 (95% confidence interval [CI], .03-2.66; P = .27). The N291S polymorphism was not significantly correlated with CVD either; the OR between the control subjects and CVD patients was 1.2 (95% CI, .07-19.46; P = .89). And the T495G mutation was not significantly correlated with CVD; the OR between the control subjects and the CVD patients was 1.21 (95% CI, .7-2.08; P = .48). CONCLUSIONS: In the present study, the D9N, N291S, and T495G polymorphisms of the LPL gene were not risk factors for the development of CVD.
Subject(s)
Cerebral Infarction/genetics , Genetic Predisposition to Disease/genetics , Lipoprotein Lipase/genetics , Polymorphism, Genetic/genetics , Aged , Aged, 80 and over , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Risk FactorsABSTRACT
BACKGROUND & AIMS: Obesity is associated with neoplasia, possibly via insulin-mediated cell pathways that affect cell proliferation. Metformin has been proposed to protect against obesity-associated cancers by decreasing serum insulin. We conducted a randomized, double-blind, placebo-controlled, phase 2 study of patients with Barrett's esophagus (BE) to assess the effect of metformin on phosphorylated S6 kinase (pS6K1), a biomarker of insulin pathway activation. METHODS: Seventy-four subjects with BE (mean age, 58.7 years; 58 men [78%; 52 with BE >2 cm [70%]) were recruited through 8 participating organizations of the Cancer Prevention Network. Participants were randomly assigned to groups given metformin daily (increasing to 2000 mg/day by week 4, n = 38) or placebo (n = 36) for 12 weeks. Biopsy specimens were collected at baseline and at week 12 via esophagogastroduodenoscopy. We calculated and compared percent changes in median levels of pS6K1 between subjects given metformin vs placebo as the primary end point. RESULTS: The percent change in median level of pS6K1 did not differ significantly between groups (1.4% among subjects given metformin vs -14.7% among subjects given placebo; 1-sided P = .80). Metformin was associated with an almost significant reduction in serum levels of insulin (median -4.7% among subjects given metformin vs 23.6% increase among those given placebo, P = .08) as well as in homeostatic model assessments of insulin resistance (median -7.2% among subjects given metformin vs 38% increase among those given placebo, P = .06). Metformin had no effects on cell proliferation (on the basis of assays for KI67) or apoptosis (on the basis of levels of caspase 3). CONCLUSIONS: In a chemoprevention trial of patients with BE, daily administration of metformin for 12 weeks, compared with placebo, did not cause major reductions in esophageal levels of pS6K1. Although metformin reduced serum levels of insulin and insulin resistance, it did not discernibly alter epithelial proliferation or apoptosis in esophageal tissues. These findings do not support metformin as a chemopreventive agent for BE-associated carcinogenesis. ClinicalTrials.gov number, NCT01447927.
Subject(s)
Barrett Esophagus/complications , Barrett Esophagus/drug therapy , Cell Proliferation/drug effects , Esophageal Neoplasms/prevention & control , Metformin/administration & dosage , Adult , Aged , Aged, 80 and over , Barrett Esophagus/pathology , Double-Blind Method , Endoscopy, Digestive System , Female , Humans , Insulin/blood , Male , Middle Aged , Placebos/administration & dosage , Prospective Studies , Ribosomal Protein S6 Kinases/analysis , Young AdultABSTRACT
BACKGROUND/AIMS: Breast cancer is the most common gynecologic malignancy known worldwide. The consumption of certain foods may modify the risk for its development. Peanuts and other seeds have shown anticarcinogenic effects in vitro, but there are a few studies that evaluate the effect of their consumption on the development of breast cancer. The aim of the present study was to determine whether there is an association between the consumption of peanuts, walnuts, and almonds and the development of breast cancer. METHODS: We analyzed 97 patients presenting with breast cancer and 104 control subjects that did not have the pathology (BIRADS 1-2). An analysis of the main clinical characteristics and lifelong seed consumption was carried out. The association between the consumption of these foods and the risk for breast cancer was estimated by odds ratios and 95% confidence intervals, controlling other risk factors, using the Mantel-Haenszel analysis. RESULTS: The high consumption of peanuts, walnuts, or almonds significantly reduced the risk for breast cancer by 2-3 times. This protective effect was not found with low or moderate seed consumption when compared with null consumption. CONCLUSIONS: High consumption of peanuts, walnuts, and almonds appears to be a protective factor for the development of breast cancer.
Subject(s)
Arachis , Breast Neoplasms/prevention & control , Diet , Juglans , Prunus dulcis , Breast Neoplasms/epidemiology , Female , Humans , Middle Aged , Protective FactorsABSTRACT
The proliferation of medical marijuana (MM) dispensaries has led to concerns that they will lead to more widespread use of marijuana. The aim of the current study was to collect descriptive data on individuals using MM dispensaries in Los Angeles County. A mixed-method approach was employed that consisted of focus groups with 30 individuals and a survey of dispensary users (N = 182) in Los Angeles County. Differences between younger (less than 30 years old) and older individuals were examined in the survey sample. Most individuals in both samples had initiated marijuana use in adolescence. Nearly one-half of survey respondents had indications of risky alcohol use and one-fifth reported recent use of illicit drugs or misuse of prescription medications. Younger individuals had higher rates of tobacco use, visited dispensaries more frequently, and had more socially embedded patterns of use, but they were similar to older individuals in terms of their reasons for use. Nearly all participants believed that MM was beneficial in treating their health problems, although 65% reported symptoms of psychological distress in the past year. Interventions aimed at MM users should stress the related effects of tobacco and risky alcohol use as well as mental health needs.