Multidrug-resistant bacterial infections after liver transplantation: Prevalence, impact, and risk factors.

BACKGROUND & AIMS: Infections by multidrug-resistant bacteria (MDRB) are an increasing healthcare problem worldwide. This study analyzes the incidence, burden, and risk factors associated with MDRB infections after liver transplant(ation) (LT). METHODS: This retrospective, multicenter cohort study included adult patients who underwent LT between January 2017 and January 2020. Risk factors related to pre-LT disease, surgical procedure, and postoperative stay were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of MDRB infections within the first 90 days after LT. RESULTS: We included 1,045 LT procedures (960 patients) performed at nine centers across Spain. The mean age of our cohort was 56.8 ± 9.3 years; 75.4% (n = 782) were male. Alcohol-related liver disease was the most prevalent underlying etiology (43.2.%, n = 451). Bacterial infections occurred in 432 patients (41.3%) who presented with a total of 679 episodes of infection (respiratory infections, 19.3%; urinary tract infections, 18.5%; bacteremia, 13.2% and cholangitis 11%, among others). MDRB were isolated in 227 LT cases (21.7%) (348 episodes). Enterococcus faecium (22.1%), Escherichia coli (18.4%), and Pseudomonas aeruginosa (15.2%) were the most frequently isolated microorganisms. In multivariate analysis, previous intensive care unit admission (0-3 months before LT), previous MDRB infections (0-3 months before LT), and an increasing number of packed red blood cell units transfused during surgery were identified as independent predictors of MDRB infections. Mortality at 30, 90, 180, and 365 days was significantly higher in patients with MDRB isolates. CONCLUSION: MDRB infections are highly prevalent after LT and have a significant impact on prognosis. Enterococcus faecium is the most frequently isolated multi-resistant microorganism. New pharmacological and surveillance strategies aimed at preventing MDRB infections after LT should be considered for patients with risk factors. IMPACT AND IMPLICATIONS: Multidrug-resistant bacterial infections have a deep impact on morbidity and mortality after liver transplantation. Strategies aimed at improving prophylaxis, early identification, and empirical treatment are paramount. Our study unveiled the prevalence and main risk factors associated with these infections, and demonstrated that gram-positive bacteria, particularly Enterococcus faecium, are frequent in this clinical scenario. These findings provide valuable insights for the development of prophylactic and empirical antibiotic treatment protocols after liver transplantation.

Overview of Cellular and Soluble Mediators in Systemic Inflammation Associated with Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease in Western countries, affecting approximately 25% of the adult population. This condition encompasses a spectrum of liver diseases characterized by abnormal accumulation of fat in liver tissue (non-alcoholic fatty liver, NAFL) that can progress to non-alcoholic steatohepatitis (NASH), characterized by the presence of liver inflammation and damage. The latter form often coexists with liver fibrosis which, in turn, may progress to a state of cirrhosis and, potentially, hepatocarcinoma, both irreversible processes that often lead to the patient's death and/or the need for liver transplantation. Along with the high associated economic burden, the high mortality rate among NAFLD patients raises interest, not only in the search for novel therapeutic approaches, but also in early diagnosis and prevention to reduce the incidence of NAFLD-related complications. In this line, an exhaustive characterization of the immune status of patients with NAFLD is mandatory. Herein, we attempted to gather and compare the current and relevant scientific evidence on this matter, mainly on human reports. We addressed the current knowledge related to circulating cellular and soluble mediators, particularly platelets, different leukocyte subsets and relevant inflammatory soluble mediators.

Cytomegalovirus specific polyfunctional T-cell responses expressing CD107a predict control of CMV infection after liver transplantation.

Cytomegalovirus (CMV) viral load after liver transplantation (LT) is controlled by cell mediated immune responses (CMI). Quantification of CMV-specific T-cells may identify patients who control CMV spontaneously and avoid expensive and potentially toxic antiviral therapies. Prospective post-LT clinical, virological and immunological monitoring was carried out up to 1-year post-LT in a cohort of adult recipients. The CMV-specific T-cell response was characterized using flow cytometry intracellular cytokine staining in 49 LT recipients-R (79.6% R+, 20.4% R-). CMV infection occurred in 24 patients (18 D+/R+ and 6 D+/R-). Only patients with undetectable polyfunctional CMV-specific CD4+ T-cells developed CMV infection. Predictive models showed that polyfunctional CMV-specific CD4+ T-cells pre-existing before LT are protective for CMV reactivation posttransplantation. Quantitation of CD4+ T-cell responses to CMV may be a useful marker for spontaneous control of viral replication to tailor antiviral prophylaxis after LT.

Effect of the dietary linoleic/α-linolenic ratio (n6/n3) on histopathological alterations caused by suboptimal temperature in tilapia (Oreochromis niloticus).

Tilapias are produced worldwide, including subtropical areas. In turn, dietary fatty acids can enhance resistance under cold stress. The present study reports the nutritional effect on suboptimal temperature tolerance based on histopathological alterations in tilapia (Oreochromis niloticus). Fish (initial weight: 34.02 ±â€¯0.79) were exposed to two different temperatures (20 °C and 30 °C) for 30 days. Under both conditions, fish were fed two different diets based on the linoleic/α-linolenic ratio (n6/n3 = 12.02 and n6/n3 = 3.85). The most important alterations in liver caused by temperature included high cellular hyperplasia in fish at 30 °C (P < 0.05). Suboptimal temperature also caused gills aneurysm, lamellar lifting and low hyperplasia (P < 0.05). Cytoplasmic vacuolization decreased and nuclear displacement increased in the fish fed n6/n3 = 3.85 (P < 0.05). Suboptimal temperature provided high gills aneurysm, epithelial lamellae lifting and low lamellar hyperplasia (P < 0.05). Conversely, the fatty acid content (n6/n3 = 3.85) in the diet provided low lamellar lifting and fusions (P < 0.05). Finally, tilapia showed an increased glycogen storage trend in gills and muscle at low temperature (P < 0.05). Our study suggests that when feeding tilapia a high dietary n3 content, this fish is able to respond to suboptimal temperature in subtropical aquaculture facilities.

Cytomegalovirus reactivation in liver transplant recipients due to hepatitis C cirrhosis is associated with higher cardiovascular risk - an observational, retrospective study.

The association between cytomegalovirus (CMV) reactivation and cardiovascular risk has been reported in solid organ transplant populations; however, it has yet to be assessed in liver transplantation (LT). We aim to evaluate whether CMV reactivation is associated with cardiovascular events (CVE) in HCV-LT patients. LT patients (2010 and 2014) due to HCV cirrhosis were included. Clinically significant CMV (CS-CMV) was defined as viral load (VL) >5000 copies/ml, need of therapy or CMV disease. Baseline variables and endpoint measures (CVE, survival, severe recurrent hepatitis C, de novo tumors, and diabetes) were collected. One hundred and forty patients were included. At LT, a history of AHT was present in 23%, diabetes 22%, tobacco use 45%, obesity 20%, and renal impairment (eGFR < 60 ml/min) in 26.5%. CS-CMV reactivation occurred in 25% of patients. Twenty-six patients (18.5%) developed a CVE. Cox regression analysis revealed two factors significantly associated with CVE: Pre-LT DM [HR = 4.6 95% CI (1.6, 13), P = 0.004] and CS-CMV [HR = 4.7 95% CI (1.8, 12.5), P = 0.002]. CS-CMV was not independently associated with the remaining endpoints except for survival (P = 0.03). In our series, CS-CMV reactivation was associated with a greater risk of developing CVE, thus confirming data from other solid organ transplant populations and emphasizing the need for adequate CMV control.

External validation of models to predict hepatocellular carcinoma in Hepatitis C Virus cured F3-F4 patients.

BACKGROUND & AIMS: Several hepatocellular carcinoma (HCC) risk-models have been developed to individualise patient surveillance following sustained viral response (SVR) in Hepatitis C Virus patients. Validation of these models in different cohorts is an important step to incorporate a more personalised risk assessment in clinical practice. We aimed at applying these models to stratify the risk in our patients and potentially determine cost-saving associated with individualised HCC risk-stratification screening strategy. METHODS: Patients with baseline F3-4 fibrosis treated with new oral direct-acting antivirals who had reached a SVR were regularly followed as part of the HCC surveillance strategy. Six models were applied: Pons, aMAP, Ioannou, HCC risk, Alonso and Semmler. Validation of the models was performed based on sensitivity and the proportion of patients labelled as "high risk". RESULTS: After excluding 557 with less than 3 fibrosis, 12 without SVR, 18 with a follow up (FU) <1 year, 17 transplant recipients, 16 lost to FU and 31 with HCC at time of antiviral therapy, our cohort consisted of 349 F3-4 SVR patients. Twenty-three patients (6.6%) developed HCC after a median FU of 5.12 years. The sensitivity of the different models varied between 0.17 (Semmler7noalcohol) and 1 (Alonso A and aMAP). The lowest proportion of high-risk patients corresponded to the Semmler-noalcohol model (5%). Sixty-three and 90% of the Alonso A and aMAP patients, respectively were labelled as high risk. The most reliable HCC risk-model applied to our cohort to predict HCC development is the Alonso model (based on fibrosis stage assessed by liver stiffness measurements or Fibrosis-4 index (FIB-4) at baseline and after 1 year, and albumin levels at 1 year) with a-100% sensitivity in detecting HCC among those at high risk and 63% labelled as high risk. The application of the model would have saved the cost of 1290 ultrasound no longer being performed in the 37% low-risk group. CONCLUSION: In our cohort, the Alonso A model allows the most reliable reduction in HCC screening resulting in safely stopping life-long monitoring in about a third of F3-F4 patients achieving SVR with DAAs.

Cirrhosis is associated with lower serological responses to COVID-19 vaccines in patients with chronic liver disease.

Background & Aims: The response of patients with chronic liver disease (CLD) to COVID-19 vaccines remains unclear. Our aim was to assess the humoral immune response and efficacy of two-dose COVID-19 vaccines among patients with CLD of different aetiologies and disease stages. Methods: A total of 357 patients were recruited in clinical centres from six European countries, and 132 healthy volunteers served as controls. Serum IgG (nM), IgM (nM), and neutralising antibodies (%) against the Wuhan-Hu-1, B.1.617, and B.1.1.529 SARS-CoV-2 spike proteins were determined before vaccination (T0) and 14 days (T2) and 6 months (T3) after the second-dose vaccination. Patients fulfilling inclusion criteria at T2 (n = 212) were stratified into 'low' or 'high' responders according to IgG levels. Infection rates and severity were collected throughout the study. Results: Wuhan-Hu-1 IgG, IgM, and neutralisation levels significantly increased from T0 to T2 in patients vaccinated with BNT162b2 (70.3%), mRNA-1273 (18.9%), or ChAdOx1 (10.8%). In multivariate analysis, age, cirrhosis, and type of vaccine (ChAdOx1 > BNT162b2 > mRNA-1273) predicted 'low' humoral response, whereas viral hepatitis and antiviral therapy predicted 'high' humoral response. Compared with Wuhan-Hu-1, B.1.617 and, further, B.1.1.529 IgG levels were significantly lower at both T2 and T3. Compared with healthy individuals, patients with CLD presented with lower B.1.1.529 IgGs at T2 with no additional key differences. No major clinical or immune IgG parameters associated with SARS-CoV-2 infection rates or vaccine efficacy. Conclusions: Patients with CLD and cirrhosis exhibit lower immune responses to COVID-19 vaccination, irrespective of disease aetiology. The type of vaccine leads to different antibody responses that appear not to associate with distinct efficacy, although this needs validation in larger cohorts with a more balanced representation of all vaccines. Impact and Implications: In patients with CLD vaccinated with two-dose vaccines, age, cirrhosis, and type of vaccine (Vaxzevria > Pfizer BioNTech > Moderna) predict a 'lower' humoral response, whereas viral hepatitis aetiology and prior antiviral therapy predict a 'higher' humoral response. This differential response appears not to associate with SARS-CoV-2 infection incidence or vaccine efficacy. However, compared with Wuhan-Hu-1, humoral immunity was lower for the Delta and Omicron variants, and all decreased after 6 months. As such, patients with CLD, particularly those older and with cirrhosis, should be prioritised for receiving booster doses and/or recently approved adapted vaccines.

Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant.

BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level.

[Renal sympathetic denervation for treatment of resistant hypertension]. / Ablação da atividade simpática renal para tratamento da hipertensão arterial resistente.

Hypertension is an important cardiovascular risk factor and although there have been many improvements in pharmacological treatment, a significant percentage of patients are still considered resistant. The authors describe two cases of radiofrequency renal sympathetic denervation that illustrate the feasibility of this new technique for the treatment of resistant hypertension. The procedure consists of the application of radiofrequency energy inside the renal arteries to ablate afferent and efferent sympathetic renal activity, which has been implicated in the pathophysiology of hypertension.

Virtual Screening and Molecular Docking: Discovering Novel c-KIT Inhibitors.

Gastrointestinal stromal tumors (GISTs) are unusual cancers, which are developed in specialized cells in the gastrointestinal tract wall. Various strategies involving single-agents, combinations, and rapid complementary inhibitor cycling are now being used to control such tumors. Based on promising early clinical trial experience, certain novel KIT and PDGFRA tyrosine kinase inhibitors have shown advanced clinical development. Resistance to tyrosine kinase inhibitors has brought immense difficulties, with patients now requiring additional therapeutic options. This review describes and discusses the last five years (2016-2020) in developing novel c-KIT kinase inhibitors using virtual screening and docking approaches. Computational techniques can be used to complement experimental studies to identify new candidate molecules for therapeutic use. Molecular modeling strategies allow the analysis of the required characteristics that compounds must have to effectively bind c-KIT. Through such analyses, it is possible to both discover and design novel inhibitors against cancer-related proteins that play a critical role in tumor development (including mutant strains). Docking showed potential in the detection of the key residues responsible for ligand recognition and is very helpful to understand the interactions in the active site that can be used to develop new compounds/classes of anticancer drugs and help millions of cancer patients.

Evidence of Nest Reactivation and Perennial Colonies in the Neotropical Bumble Bee Bombus brevivillus (Hymenoptera: Apidae: Bombini).

Bombus brevivillus Franklin is a Neotropical Bombus species whose colonies are disappearing from most of its native range, and little is known about its biology and reproductive habits to help conservation or breeding efforts. Unlike Bombus species from temperate climates whose colonies perish every winter, there are suggestions of perennial colonies that Neotropical Bombus species can present. In this work, we investigated the development of two B. brevivillus colonies (i.e., number of workers, gynes, males, new cocoons, and brood area) between August 2012 and March 2013. We realized that while one colony collapsed and died after the males' and gynes' production, and the reduction of numbers of adult workers, in the other, a new queen assumed the posture at this phase and reactivated the old nest. Despite the reduced number of colonies investigated, this study shows the possibility of nest reactivation in the studied species in queen supersedure events in resemblance to perennial colonies of eusocial bees like Apis species and stingless bees. Such behavior has never been directly described to B. brevivillus in previous studies and opens the possibility for further research in the existence and the extension of perennial colonies in Neotropical Bombus species due to its importance to the species conservation in the tropical environment.

One-quarter of chronic hepatitis D patients reach HDV-RNA decline or undetectability during the natural course of the disease.

BACKGROUND: Spontaneous HDV-RNA fluctuations, assessed by nonstandardised in-house assays, have been reported during the course of chronic hepatitis delta (CHD). AIMS: To evaluate changes in serum HDV-RNA concentrations in untreated CHD patients and correlate these changes with other HBV markers. METHODS: A total of 323 consecutive serum samples from 56 CHD patients (detectable HDV-RNA) followed for >3 years were retested for HDV-RNA levels by a sensitive technique using the first WHO international HDV-RNA standard. Quantitative HBsAg, HBV-DNA, and HBV-RNA were also determined. RESULTS: Most participants were male, middle-aged, white European, and HBeAg-negative (82%). Almost half had liver cirrhosis and 64% were receiving nucleos(t)ide analogues. At inclusion, median-HDV-RNA was 5.3 (4.2-6.5) log10 IU/mL, HBsAg 4.0 (3.5-4.3) log10 IU/mL, and HBV-DNA 1.6 (1.0-2.6) log10 IU/mL; ALT values were normal in 13 (23%). During a mean follow-up of 5.6 (3-16) years, 14 (25%) showed ≥2log10 HDV-RNA decline, including 11 (20%) who spontaneously achieved undetectable HDV-RNA. Four patients (7%) lost HBsAg, with undetectable HDV-RNA. The remaining 42 (75%) had persistently detectable HDV-RNA. During follow-up, patients with a ≥2log10 HDV-RNA decline showed a greater HBsAg drop (-0.7 ± 1.1 vs -0.09 ± 0.9 log IU/mL; P = 0.039) than those with a <2 log10 HDV-RNA decline. Overall, ALT and HBV-DNA levels decreased over time. There were no differences in clinical outcomes between groups. CONCLUSIONS: One-quarter of untreated CHD patients showed a ≥2log10 decline in HDV-RNA and 20% reached HDV-RNA undetectability during a mean follow-up of 5.6 years. The decline was associated with ALT decrease. These findings have implications for designing new therapies for CHD.

A population-based screening for hepatitis C antibodies and active infection using a point-of-care test in a low prevalence area.

BACKGROUND: Data on the true prevalence of hepatitis C virus (HCV) infection in the general population is essential. We evaluated a program implementing free universal HCV screening using a non-invasive point-of-care test (POCT) (OraQuick-HCV rapid test) in oral fluid in an urban area in Valencia, South-Eastern Spain. METHODS: A cross-sectional study was performed during 2015-2017. Free HCV screening was offered by regular mail to 11,500 individuals aged 18 and over, randomly selected from all census residents in the Health Department. All responding participants filled in a questionnaire about HCV infection risk factors and were tested in their tertiary Hospital. In those with a positive POCT, results were confirmed by enzyme-immunoassay and HCV-RNA. RESULTS: 1,206 persons agreed to participate (response rate: 11.16%). HCV antibodies were detected in 19 (1.60%) cases (age-sex standardized rate: 1.31%; 95%CI: 0.82-2.07), but only 8 showed positive HCV-RNA (age-sex standardized rate: 0.56%; 95%CI: 0.28-1.14). The majority (89%) of the cases were born before 1965 and 74% had at least one known risk factor for HCV infection. All anti-HCV positive individuals were already aware of their infection, and no undiagnosed cases were detected. The performance of the POCT was excellent for detecting active infection. CONCLUSIONS: These preliminary data suggest that HCV population screening with a POCT is feasible but, in our setting, mailing recruiting is not effective (11% response rate). The low prevalence of HCV antibodies and active infection in the participant population (with no new diagnoses made) suggests that, in our setting, underdiagnosis may be uncommon.

Reflections and collective production about being a municipal health counselor.

OBJECTIVE: to identify the participation dynamics of a municipal council and to develop a critical-reflexive process on "being a counselor", identifying weaknesses and possibilities of this council, in addition to collectively generating new knowledge and (re)elaborating the MHC Ordinary Law. METHOD: Convergent care research, including documentary analysis, non-participant observation and thematic workshops. The research was carried out in 2016, with municipal health counselors from a city in the Western Region of Santa Catarina. RESULTS: this study made it possible to identify forms of social participation that should be strengthened in the performance of social power, to reflect and share individual experiences, to anchor them in the current legislation, and to build knowledge that enabled the elaboration/organization of a product - a new text for the Ordinary Law of the Council, adjusted to current legislation. FINAL CONSIDERATIONS: There is a need to increase participation, considering the presence of the counselors in the meetings, the effective representation and a greater interaction in the discussions and deliberations of the council.

Análise do índice de vulnerabilidade, equilíbrio e depressão em idosos praticantes e não praticantes de atividade física após o período de isolamento social na pandemia da Covid-19 / Analysis of the index of vulnerability, balance and depression in elderly people who practice and non-practice of physical activity after the period of social isolation during the COVID-19 pandemic

Idosos são suscetíveis a formas graves da Covid-19, o que resultou em medidas de isolamento social que intensificaram o estilo de vida sedentário, com comprometimento emocional e funcional. A atenção primária deve preparar-se para lidar com as repercussões desse período. Risco de quedas, rastreio de sintomas depressivos e vulnerabilidade são preditores de redução da capacidade funcional em idosos. Objetivo: Comparar o índice de vulnerabilidade, equilíbrio, depressão em idosos praticantes e não praticantes de atividade física após o período de isolamento social na pandemia da Covid-19. Casuística e Métodos: Estudo analítico transversal comparativo, com amostragem não probabilística voluntária de 56 idosos vinculados a um programa comunitário de saúde de uma capital brasileira, sendo 28 participantes do Grupo Fisioterapia (GF) e 28 do Grupo Sedentários (GS), com período de coleta de dados entre agosto a novembro de 2022. Utilizou-se questionários sociodemográficos de autopercepção de saúde e do estado emocional pela Geriatric Depression Scale (GDS-30), de classificação do nível de vulnerabilidade pelo Índice de vulnerabilidade Clínico-Funcional-20 (IVCF-20) e de risco de quedas e avaliação do equilíbrio pelo Timed Up and Go Test (TUG). Resultados: Média de idade de 69,36 ± 6,97 anos com predominância feminina (76,8%). Significância estatística entre grupos para escores GDS-30 e TUG (p=0,03; p<0,01) que evidenciaram depressão moderada em ambos os grupos e risco para quedas no GS. A média do IVCF-20 dos grupos revelou baixo comprometimento quanto à vulnerabilidade. O GF apresentou menores índices em todos os casos. Conclusão: A atividade física mostrou-se um modelo de intervenção que impacta na autonomia e bem-estar dos idosos, com melhores escores de vulnerabilidade, mobilidade funcional e depressão

Elderly are susceptible to severe forms of Covid-19 and this led to social isolation measures that intensified a sedentary lifestyle, with emotional and functional impairment. Primary care must prepare to deal with the repercussions of this period. Risk of falls, screening for depressive symptoms and vulnerability are predictors of reduced functional capacity in the elderly. Objective: To compare the vulnerability index, balance, depression in elderly practitioners and non-practitioners of physical activity after the period of social isolation of the Covid-19 pandemic. Casuistic and Methods: Comparative cross-sectional analytical study, with voluntary nonprobabilistic sampling of 56 elderly people linked to a community health program in a Brazilian capital, with 28 participants in the Physical Therapy Group (GF) and 28 in the Sedentary Group (GS), with a collection period between August and November 2022. Socio-demographic questionnaires were used to assess self-perception of health and emotional state using the Geriatric Depression Scale (GDS-30), classification of vulnerability level using the Clinical-Functional Vulnerability Index-20 (IVCF-20) and risk of falls and assessment of balance by the Timed Up and Go Test (TUG). Results: Mean age of 69.36 ± 6.97 years, with female predominance (76.8%). Statistical significance between groups for GDS-30 and TUG scores (p=0.03; p<0.01), which showed moderate depression in both groups and risk for falls in the GS. The IVCF-20 average of the groups revealed low impairment in terms of vulnerability. The GF had lower rates in all cases. Conclusion: Physical activity proved to be an intervention model that impacts the autonomy and well-being of the elderly, with better vulnerability scores, functional mobility and depression

Performance of the OraQuick Hepatitis C virus antibody test in oral fluid and fingerstick blood before and after treatment-induced viral clearance.

BACKGROUND: A reliable population screening strategy for hepatitis C virus (HCV) infection may be based in easy-to-use point-of-care (POC) tests for HCV antibodies, but validation data is needed before their potential widespread use in primary care or outreach practice. Besides, the sensitivity of these POC tests in patients with spontaneous or treatment-induced viral clearance is unknown. OBJECTIVES: To test the performance of a non-invasive POC anti-HCV test (OraQuick HCV rapid test) in oral mucosal transudate (OMT) and fingerstick blood from patients with known anti-HCV serostatus and with or without active viremia (after treatment-induced clearance). STUDY DESIGN: A risk factor questionnaire was collected from 317 consecutive patients (anti-HCV positive/HCV-RNA positive n = 107; anti-HCV positive/HCV-RNA negative after antiviral treatment n = 107; anti-HCV negative with other liver diseases n = 109) before performing the OraQuick HCV rapid test in OMT (n = 317) and fingerstick blood (n = 251). We calculated the sensitivity and specificity of the test by using anti-HCV serostatus as the reference gold-standard. RESULTS: Among all anti-HCV seropositive patients, the clinical sensitivity and specificity of the OraQuick HCV rapid test in OMT was 89.9% and 100%, respectively. In fingerstick blood, the sensitivity improved to 98.8%. The sensitivity was higher in OMT (97.2%) in anti-HCV seropositive patients who were viremic as compared to that in non-viremic individuals (82.2%). In contrast, there were no significant differences in sensitivity between viremic and non-viremic individuals when testing fingerstick blood. Finally, extension of the read time to 40 min enhanced the sensitivity, especially in OMT (up to 94.7%) and in the subgroup of non-viremic, anti-HCV-positive patients (up to 90.1%). CONCLUSIONS: The OraQuick HCV rapid test in OMT has a high sensitivity and specificity for detecting active HCV infection that decreases substantially in anti-HCV positive/HCV-RNA negative patients with treatment-induced viral clearance. For these individuals, extension of read times and testing fingerstick blood showed improved sensitivity.

Proposal for a universal measurement system for school chairs and desks for children from 6 to 10 years old.

In a primary education classroom of any country, children of the same age have very different statures, reaching variations of 200 mm (Gonçalves, 2012). However, the school furniture provided is not suitable or adaptable to these differences. Designing school furniture able to respond to these variations is, therefore, a challenge for ergonomics and design in a global market. It is clearly not viable for industries to adapt productions for each country. When competitiveness and limitation of resources are essential for the viability of any product it becomes essential to find a universal system adapted to the requisites of any country. Taking as prescription measure the popliteal height obtained from the data of different countries, a universal measurement system for the school chair and desk set is proposed, combining the ellipse methodology used by Molenbroek et al. (2003) and the (mis)match equations mentioned by Castellucci et al. (2014b). From the results obtained, it can be concluded that only 5 sizes are needed to implement this new measurement system of evolutionary school furniture for the primary education classroom.

Real-time cytometric assay of nitric oxide and superoxide interaction in peripheral blood monocytes: A no-wash, no-lyse kinetic method.

BACKGROUND: Nitric oxide (NO) and its related reactive nitrogen species (RNS) and reactive oxygen species (ROS) are crucial in monocyte responses against pathogens and also in inflammatory conditions. Central to both processes is the generation of the strong oxidant peroxynitrite (ONOO) by a fast reaction between NO and superoxide anion. ONOO is a biochemical junction for ROS- and RNS cytotoxicity and causes protein nitrosylation. Circulating by-products of protein nitrosylation are early biomarkers of inflammation-based conditions, including minimal hepatic encephalopathy in cirrhotic patients (Montoliu et al., Am J Gastroenterol 2011; 106:1629-1637). In this context, we have designed a novel no-wash, no-lyse real-time flow cytometry assay to detect and follow-up the NO- and superoxide-driven generation of ONOO in peripheral blood monocytes. METHODS: Whole blood samples were stained with CD45 and CD14 antibodies plus one of a series of fluorescent probes sensitive to RNS, ROS, or glutathione, namely 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate, dihydrorhodamine 123, MitoSOX Red, dihydroethidium, and 5-chloromethylfluorescein diacetate. Samples were exposed sequentially to a NO donor and three different superoxide donors, and analyzed in real time by kinetic flow cytometry. Relevant kinetic descriptors, such as the rate of fluorescence change, were calculated from the kinetic plot. RESULTS: The generation of ONOO, which consumes both NO and superoxide, led to a decrease in the intensity of the cellular fluorescence of the probes sensitive to these molecules. CONCLUSION: This is a fast and simple assay that may be used to monitor the intracellular generation of ONOO in physiological, pathological, and pharmacological contexts. © 2015 International Clinical Cytometry Society.

Oxidative imbalance in low/intermediate-1-risk myelodysplastic syndrome patients: The influence of iron overload.

OBJECTIVE: To assess the generation of reactive oxygen species (ROS) and the involvement of the main antioxidant pathways in low/intermediate-1-risk myelodysplastic syndromes (MDS) with iron overload (IOL). METHODS: We examined the levels of superoxide anion (O2-), hydrogen peroxide (H2O2), antioxidants (glutathione, GSH; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx), mitochondrial membrane potential (ΔΨm), and by-products of oxidative damage (8-isoprostanes and 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxo-dG) in 42 MDS patients (28 without IOL at diagnosis, and 14 who developed IOL) and 20 healthy subjects. RESULTS: Patients with IOL showed higher O2- levels (39.4 MFI) than normal controls (22.7 MFI, p=0.0356) and patients at diagnosis (19.4 MFI, p=0.0049). Antioxidant systems, except SOD activity, exhibited significant changes in IOL patients with respect to controls (CAT: 7.1 vs 2.7nmol/ml/min, p=0.0023; GPx: 50.9 vs 76.4nmol/ml/min, p=0.0291; GSH: 50.2 vs 24.1 MFI, p=0.0060). Furthermore, mitochondrial dysfunction was only detected in IOL cases compared to controls (ΔΨm: 3.6 vs 6.4 MFI, p=0.0225). Finally, increased levels of 8-oxo-dG were detected in both groups of patients. CONCLUSION: Oxidative stress is an important but non-static phenomenon in MDS disease, whose status is influenced by, among other factors, the presence of injurious iron.

WITHDRAWN: Systems Biology and Immune Aging.

The Publisher regrets that this article is an accidental duplication of anarticle that has already been published, http://dx.doi.org/10.1016/j.imlet.2014.09.009. The duplicate article has therefore been withdrawn.