Impacto de los residuos de ivermectina en los procesos tecnológicos de la leche y sus derivados

Se evaluó la estabilidad química de los residuos de ivermectina (IVM, fármaco antiparasitario) en leches bovina y ovina. La estabilidad del fármaco se midió mediante cromatografía liquida de alta performance analizando muestras de leche con residuos de IVM antes y después del tratamiento térmico. Además se evaluó, mediante la prueba del yogur y estudios microbiológicos de recuento de bacterias lácticas, el efecto de los residuos sobre la viabilidad de las bacterias ácido lácticas. Los residuos de IVM en leche demostraron ser estables a los tratamientos térmicos utilizados en la industria láctea de pasteurización: baja temperatura/largo tiempo (LTLT 65ºC, 30 min) y alta temperatura/corto tiempo (HTST 75ºC, 15 s). Los procesos de industrialización de la leche basados en la actividad de las bacterias lácticas tampoco fueron afectados por la presencia de residuos de IVM. Las concentraciones evaluadas no modificaron el incremento de la acidez en la prueba del yogur y no disminuyeron los recuentos de bacterias lácticas presentes en muestras de yogures elaborados con residuos del antiparasitario. El impacto de los residuos de fármacos antiparasitarios en los procesos tecnológicos de elaboración de alimentos y en la salud del consumidor a largo plazo debe ser cuidadosamente analizado.Chemical stability of ivermectin residues (IVM, antiparasitic drug) in cattle and sheep milk was evaluated. IVM residues were measured in milk samples before and after heat treatment by high performance liquid chromatography. Additionally, the effect of drug residues on the lactic acid fermentation was assessed by testing the viability and counts of lactic acid bacteria. IVM concentrations in milk were stable after standard procedures used in dairy industry LTLT pasteurization (65°C, 30 min) and HTST (75°C, 15 s). Industrial milk processing based on the activity of lactic acid bacteria was not affected by the presence of IVM residues. IVM concentrations did not affect the increment of acidity nor the number of lactic acid bacteria in yogurt samples. The impact of the residues of antiparasitic drugs in technological processes of food processing and consumer health must be carefully analyzed to avoid long-term consequences

Prevalence of Advanced, Precancerous Colorectal Neoplasms in Black and White Populations: A Systematic Review and Meta-analysis

Background & Aims Colorectal cancer (CRC) incidence and mortality are higher in black vs white populations. The reasons for these disparities are not clear, yet some guidelines recommend screening black persons for CRC starting at ages 40–45 years. We performed a systematic review and meta-analysis to compare the prevalence of advanced adenomas (AAs) and advanced, precancerous colorectal neoplasms (ACNs) between asymptomatic black and white screen-eligible adults. Methods We searched Ovid MEDLINE, PubMed, Embase, and the Cochrane Library to identify articles (published from 1946 through June 2017) that reported prevalence values of AA or ACN in average-risk black and white individuals undergoing screening colonoscopy. Two authors independently assessed study quality and risk for bias using a modified validated quality assessment instrument. Following the PRISMA guidelines, 2 authors independently abstracted descriptive and quantitative data from each study. We performed a random effects meta-analysis to determine risk differences and odds ratios (ORs). Results From 1653 articles, we identified 9 studies for analysis, comprising 302,128 individuals. Six of the 9 studies were of high methodological quality, had a low risk for bias, and were included in the meta-analysis. In these 9 studies, the overall prevalence values for AA and ACN did not differ significantly between back (6.57%) and white screened individuals (6.20%; OR, 1.03; 95% CI, 0.81–1.30). Among a subgroup of 5 studies, the prevalence of proximal AA and ACN was significantly higher in black (3.30%) than in white screened individuals (2.42%; OR, 1.20; 95% CI, 1.12–1.30). Excluding the largest study did not affect overall prevalence (OR, 0.99; CI, 0.73–1.34) but eliminated the difference in prevalence of proximal AA or ACN (OR, 1.48; 95% CI, 0.87–2.52). Conclusions In a meta-analysis, we found the overall prevalence of AA and ACN did not differ significantly between average-risk black and white persons, indicating that the age at which to begin CRC screening need not differ based on race

Detection of first- and second-line drug resistance in Mycobacterium tuberculosis clinical isolates by pyrosequencing

Conventional phenotypic drug susceptibility testing (DST) methods for Mycobacterium tuberculosis are laborious and very time-consuming. Early detection of drug-resistant tuberculosis (TB) is essential for prevention and control of TB transmission. We have developed a pyrosequencing method for simultaneous detection of mutations associated with resistance to rifampin, isoniazid, ethambutol, amikacin, kanamycin, capreomycin, and ofloxacin. Seven pyrosequencing assays were optimized for following loci: rpoB, katG, embB, rrs, gyrA, and the promoter regions of inhA and eis. The molecular method was evaluated on a panel of 290 clinical isolates of M. tuberculosis. In comparison to phenotypic DST, the pyrosequencing method demonstrated high specificity (100%) and sensitivity (94.6%) for detection of multidrug-resistant M. tuberculosis as well as high specificity (99.3%) and sensitivity (86.9%) for detection of extensively drug-resistant M. tuberculosis. The short turnaround time combined with multilocus sequencing of several isolates in parallel makes pyrosequencing an attractive method for drug resistance screening in M. tuberculosis.Fil: Engström, Anna. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Swedish Institute for Communicable Disease Control; SueciaFil: Morcillo, Nora Susana. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; ArgentinaFil: Imperiale, Belén Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; ArgentinaFil: Hoffner, Sven E.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Swedish Institute for Communicable Disease Control; SueciaFil: Juréen, Pontus. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Swedish Institute for Communicable Disease Control; Sueci

Performance Characteristics of Fecal Immunochemical Tests for Colorectal Cancer and Advanced Adenomatous Polyps: A Systematic Review and Meta-analysis

Background: Studies report inconsistent performance of fecal immunochemical tests (FITs) for colorectal cancer (CRC) and advanced adenomas. Purpose: To summarize performance characteristics of FITs for CRC and advanced adenomas in average-risk persons undergoing screening colonoscopy (reference standard) and to identify factors affecting these characteristics. Data Sources: Ovid MEDLINE, PubMed, Embase, and the Cochrane Library from inception through October 2018; reference lists of studies and reviews. Study Selection: Two reviewers independently screened records to identify published English-language prospective or retrospective observational studies that evaluated FIT sensitivity and specificity for colonoscopic findings in asymptomatic, average-risk adults. Data Extraction: Two authors independently extracted data and evaluated study quality. Data Synthesis: Thirty-one studies (120 255 participants; 18 FITs) were included; all were judged to have low to moderate risk of bias. Performance characteristics depended on the threshold for a positive result. A threshold of 10 µg/g resulted in sensitivity of 0.91 (95% CI, 0.84 to 0.95) and a negative likelihood ratio of 0.10 (CI, 0.06 to 0.19) for CRC, whereas a threshold of greater than 20 µg/g resulted in specificity of 0.95 (CI, 0.94 to 0.96) and a positive likelihood ratio of 15.49 (CI, 9.82 to 22.39). For advanced adenomas, sensitivity was 0.40 (CI, 0.33 to 0.47) and the negative likelihood ratio was 0.67 (CI, 0.57 to 0.78) at 10 µg/g, and specificity was 0.95 (CI, 0.94 to 0.96) and the positive likelihood ratio was 5.86 (CI, 3.77 to 8.97) at greater than 20 µg/g. Studies had low to high heterogeneity, depending on the threshold. Although several FITs had adequate performance, sensitivity and specificity for CRC for 1 qualitative FIT were 0.90 and 0.91, respectively, at its single threshold of 10 µg/g; positive and negative likelihood ratios were 10.13 and 0.11, respectively. Comparison of 3 FITs at 3 thresholds was inconclusive: CIs overlapped, and the comparisons were across rather than within studies. Limitations: Only English-language studies were included. Incomplete reporting limited quality assessment of some evidence. Performance characteristics are for 1-time rather than serial testing. Conclusion: Single-application FITs have moderate to high sensitivity and specificity for CRC, depending on the positivity threshold. Sensitivity of 1-time testing for advanced adenomas is low, regardless of the threshold

Stereotypies in the autism spectrum disorder: Can we rely on an ethological model?

Background: Stereotypic behaviour can be defined as a clear behavioural pattern where a specific function or target cannot be identified, although it delays on time. Nonetheless, repetitive and stereotypical behaviours play a key role in both animal and human behaviour. Similar behaviours are observed across species, in typical human developmental phases, and in some neuropsychiatric conditions, such as Autism Spectrum Disorder (ASD) and Intellectual Disability. This evidence led to the spread of animal models of repetitive behaviours to better understand the neurobiological mechanisms underlying these dysfunctional behaviours and to gain better insight into their role and origin within ASD and other disorders. This, in turn, could lead to new treatments of those disorders in humans. Method: This paper maps the literature on repetitive behaviours in animal models of ASD, in order to improve understanding of stereotypies in persons with ASD in terms of characterization, pathophysiology, genomic and anatomical factors. Results: Literature mapping confirmed that phylogenic approach and animal models may help to improve understanding and differentiation of stereotypies in ASD. Some repetitive behaviours appear to be interconnected and mediated by common genomic and anatomical factors across species, mainly by alterations of basal ganglia circuitry. A new distinction between stereotypies and autotypies should be considered. Conclusions: Phylogenic approach and studies on animal models may support clinical issues related to stereotypies in persons with ASD and provide new insights in classification, pathogenesis, and management

Phenotypic features effectively stratify risk for advanced colorectal neoplasia in asymptomatic adults

poster abstractBackground: While colorectal cancer (CRC) screening is effective and cost-effective for reducing CRC incidence and mortality, it is underutilized (nearly 40% of U.S. adults are either not current with or have never been screened), inefficient (low-risk persons undergo colonoscopy), and costly to the U.S. health care system. A simple and effective way of stratifying risk for advanced neoplasia (AN – CRC and advanced, precancerous polyps) could improve the efficiency and uptake of screening by tailoring colonoscopy toward persons at highrisk and giving low-risk persons less-invasive options. Although several risk factors for AN have been identified, they are not used in clinical practice in part because of inability to integrate the factors to produce a risk estimate. Objective: To derive and validate a risk index for AN (CRC, advanced adenomas, serrated polyps >= 1 cm) anywhere in the colorectum. Methods: We measured socio-demographic features, medical and family history, lifestyle factors, and physical features in 50-80 year old persons who underwent first-time screening colonoscopy between December 2004 and September 2011, and linked these factors to endoscopic and histologic findings. Using logistic regression, we derived a risk equation on a randomly selected 2/3s of the sample. A 12-variable model was selected based on optimal statistical metrics. Based on model coefficients, we assigned points to each variable to create a risk score, which ranged from -13 to 8. Scores with comparable magnitudes of risk were collapsed into 3 risk categories. The model was tested on the remaining third of the sample. Results: Among 3025 subjects in the derivation set (mean age 57.3 ± 6.5 years; 52% women), the prevalence of AN was 9.4% (including 26 CRCs). Model variables include age, sex, smoking, ethanol use, marital status, NSAID and aspirin use, physical activity, education level, and metabolic syndrome (P-value for fit = 0.09; cstatistic=0.78). Respective risks of AN in the low- (scores of -13 to -5), intermediate- (scores of -4 to 2) and high- (scores of 3 to 12) were 1.52% (95%, 0.07-2.8%), 6.86%, and 26.8% (P-value for trend < 0.001), with respective cohort proportions of 23%, 59% and 18%. Ten low-risk subjects had AN (0 CRCs, 6 distal). Based on finding a distal sentinel polyp, sigmoidoscopy to the descending colon would have detected 7(70%) ANs. Among the 1475 subjects in the test set (mean age 57.2 ± 6.5 years; 52% women), AN prevalence was 8.4%. Risk of AN in the low-risk subgroup was 2.73% (CI, 1.25-5.11%) and was 5.57% and 25.4% in the intermediate- and high-risk subgroups, respectively (P<0.001), with cohort proportions of 23%, 59%, and 18%. Nine low-risk subjects had AN (0 CRCs, 5 distal, 6 detectable by sigmoidoscopy. Conclusion: This new risk index effectively stratifies the risk for AN among asymptomatic adults, identifying a low-risk subgroup of 23% that may be screened effectively and efficiently with tests other than colonoscopy and a high-risk subgroup of 18% in which colonoscopy may be preferable. If validated in other settings, this index could increase both the efficiency and uptake of CRC screening

Epidermal growth factor receptor (EGFR) activation induces the expression of multidrug resistance associated protein 4 (MRP4/ABCC4) in a pancreatic cancer human cell line

Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of pancreatic cancer and has one of the worse prognosis. The poor overall survival is associated with the overexpression of epidermal growth factor receptor (EGFR), a known member of the ErbB family of receptor tyrosine kinases and multidrug resistance associated protein 4 (MRP4/ABCC4). Our previous results show that high levels MRP4 are associated with increase in tumor cell proliferation, metastatic invasion and up-regulation of EGFR protein levels in PDACs cell lines. The aim of our study was to evaluate the regulation of MRP4 by EGFR activation in a pancreatic cancer cell model. To accomplish our objective, we treated the pancreatic cancer cell line BxPC-3 with EGF (0.1ng/ul). EGFR activation was confirmed by ERK phosphorylation at 5, 10, 20, 30, and 40 min after EGF treatment. MRP4 protein expression was evaluated by western blot using whole cell extracts following incubation with EGF for 0, 24 and 48 h, using histone as loading control. MRP4 expression levels were also assessed 48 h after treatment with EGF alone or in combination with the EGFR inhibitor CL 387-785 (1µM). Our results confirm that EGFR is quickly activated upon incubation with EGF, as evidenced by a 4-fold increase in the pERK/total ERK ratio detected (P<0.001) at 5 min and normalized at 40 min. Maximal induction of MRP4 expression (86%, P<0.001) was observed in cells treated with EGF for 48 h. Furthermore, EGF-mediated MRP4 induction was abolished by co-treatment with CL387-785 (P<0.05), while its expression does not change by treatment with this EGFR inhibitor alone. These data demonstrate that EGFR activation produces increments in MRP4 protein levels in a PDAC cell line. In summary, it is possible that MRP4 and EGFR, both PDAC poor prognosis markers, are co-regulated by a positive feed-back which ultimately enhances their effect upon each other.Fil: Lago, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Barosso, Ismael Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Sahores, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Imperiale, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Manautou, José E.. University of Connecticut; Estados UnidosFil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Ghanem, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaReunión Anual de la Sociedad Argentina de FisiologíaRosarioArgentinaSociedad Argentina de Fisiologí

Evaluating a Modular Decision Support Application For Colorectal Cancer Screening

BACKGROUND: There is a need for health information technology evaluation that goes beyond randomized controlled trials to include consideration of usability, cognition, feedback from representative users, and impact on efficiency, data quality, and clinical workflow. This article presents an evaluation illustrating one approach to this need using the Decision-Centered Design framework. OBJECTIVE: To evaluate, through a Decision-Centered Design framework, the ability of the Screening and Surveillance App to support primary care clinicians in tracking and managing colorectal cancer testing. METHODS: We leveraged two evaluation formats, online and in-person, to obtain feedback from a range primary care clinicians and obtain comparative data. Both the online and in-person evaluations used mock patient data to simulate challenging patient scenarios. Primary care clinicians responded to a series of colorectal cancer-related questions about each patient and made recommendations for screening. We collected data on performance, perceived workload, and usability. Key elements of Decision-Centered Design include evaluation in the context of realistic, challenging scenarios and measures designed to explore impact on cognitive performance. RESULTS: Comparison of means revealed increases in accuracy, efficiency, and usability and decreases in perceived mental effort and workload when using the Screening and Surveillance App. CONCLUSION: The results speak to the benefits of using the Decision-Centered Design approach in the analysis, design, and evaluation of Health Information Technology. Furthermore, the Screening and Surveillance App shows promise for filling decision support gaps in current electronic health records

Changes in Adult BMI and Waist Circumference Are Associated with Increased Risk of Advanced Colorectal Neoplasia

BACKGROUND: Waist circumference (WC) is a stronger predictor of colon cancer (CRC) risk than body mass index (BMI). However, how well change in either WC or BMI predicts risk of advanced colorectal neoplasia (AN) is unclear. AIMS: To determine the relationship between change in BMI and WC from early adulthood to later age and the risk of AN and which change measure is a stronger predictor. METHODS: In 4500 adults, ages 50-80, with no previous neoplasia and undergoing screening colonoscopy, BMI and WC at age 21 and at time of screening were reported. Changes in BMI and WC were defined using universal risk cutoffs. Known CRC risk factors were controlled in the logistic models. RESULTS: Overall, model statistics showed WC change (omnibus test χ 2 = 10.15, 2 DF, p value = 0.006) was a statistically stronger predictor of AN than BMI change (omnibus test χ 2 = 5.66, 5 DF, p value = 0.34). Independent of BMI change, participants who increased WC (OR 1.44; 95% CI 1.05-1.96) or maintained a high-risk WC (OR 2.50; 95% CI 1.38-4.53) at age 21 and at screening had an increased risk of AN compared to those with a low-risk WC. Study participants who were obese at age 21 and at screening had an increased risk of AN (OR 1.87; 95% CI 1.08-3.23) compared to those who maintained a healthy BMI. Maintaining an overweight BMI or increasing BMI was not associated with AN. CONCLUSIONS: Maintaining an unhealthy BMI and WC throughout adult life may increase risk of AN. WC change may be a better predictor of AN than BMI change