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Point of injection scatter (SPI) confounds breast cancer sentinel lymph node detection. Round flat lead shields (FLSs) incompletely reduce SPI, requiring repositioning. We designed lead shields that reduce SPI and acquisition time. Two concave lead shields, a semioval lead shield (OLS) and a semispherical lead alloy shield (SLS), were created with a SICNOVA JCR 1000 3D printer to cover the point of injection (patent no. ES1219895U). Twenty breast cancer patients had anterior and anterior oblique imaging, 5 minutes and 2 hours after a single 111 MBq nanocolloid in 0.2 mL intratumoral or periareolar injection. Each acquisition was 2 minutes. Absolute and normalized background corrected scatter counts (CSCs) and scatter reduction percentage (%SR) related to the FLS were calculated. Repositionings were recorded. Differences between means of %SR (t test) and between means of CSC (analysis of variance) with Holm multiple comparison tests were determined. Mean %SR was 91.8% with OLS and 92% using SLS in early images (P = 0.91) and 87.2%SR in OLS and 88.5% in late images (P = 0.66). There were significant differences between CSC using FLS and OLS (P We designed 2 concave lead shields that significantly reduce the SPI and repositioning with sentinel lymph node lymphoscintigraphy.

Point of injection scatter (SPI) confounds breast cancer sentinel lymph node detection. Round flat lead shields (FLSs) incompletely reduce SPI, requiring repositioning. We designed lead shields that reduce SPI and acquisition time.Two concave lead shields, a semioval lead shield (OLS) and a semispherical lead alloy shield (SLS), were created with a SICNOVA JCR 1000 3D printer to cover the point of injection (patent no. ES1219895U). Twenty breast cancer patients had anterior and anterior oblique imaging, 5 minutes and 2 hours after a single 111 MBq nanocolloid in 0.2 mL intratumoral or periareolar injection. Each acquisition was 2 minutes. Absolute and normalized background corrected scatter counts (CSCs) and scatter reduction percentage (%SR) related to the FLS were calculated. Repositionings were recorded. Differences between means of %SR (t test) and between means of CSC (analysis of variance) with Holm multiple comparison tests were determined.Mean %SR was 91.8% with OLS and 92% using SLS in early images (P = 0.91) and 87.2%SR in OLS and 88.5% in late images (P = 0.66). There were significant differences between CSC using FLS and OLS (P0.001) and between FLS and SLS (P0.001), but not between OLS and SLS (P = 0.17) in early images, with the same results observed in delayed studies (P0.001 in relation to FLS and P = 0.1 between both curved lead shields). Repositioning was required 14/20 times with FLS, 4/20 times with OLS, and 2/20 times with SLS.We designed 2 concave lead shields that significantly reduce the SPI and repositioning with sentinel lymph node lymphoscintigraphy.

Melanocyte-derived tumours are common in humans and animals and their spontaneous occurrence in dogs and the clinicopathological progression in malignant presentations is comparable with humans. Melanomas are a heterogeneous group of malignant neoplasms and several subtypes have been classified, including angiomatoid melanoma, of which only five cases have been reported in humans but none in animals. We now document cases of primary angiomatoid melanoma in the skin and oral cavity of two dogs. Neoplastic cells resembling endothelial cells that lined large blood vessels in the tumours were immunonegative for CD34 but intensely positive for SOX10.

Aim Assessing the effect of statin therapy (ST) at hospital admission for COVID-19 on in-hospital mortality. Methods and results Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk. Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients [1234 men, 923 women; age: 67 y/o (IQR 54–78)] admitted to the hospital were retrieved from the clinical records in anonymized manner. Three hundred and fifty-three deaths occurred. Five hundred and eighty-one patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on ST than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: P = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared with the GM non-statin group (17.4%; P = 0.045). The Cox model applied to the CSH function [HR = 0.58(CI: 0.39–0.89); P = 0.01] and the competing-risks FG model [HR = 0.60 (CI: 0.39–0.92); P = 0.02] suggest that statins are associated with reduced COVID-19-related mortality. Conclusions A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.

Graphical abstract, Background Age, sex, race and comorbidities are insufficient to explain why some individuals remain asymptomatic after SARS-CoV-2 infection, while others die. In this sense, the increased risk caused by the long-term exposure to air pollution is being investigated to understand the high heterogeneity of the COVID-19 infection course. Objectives We aimed to assess the underlying effect of long-term exposure to NO2 and PM10 on the severity and mortality of COVID-19. Methods A retrospective observational study was conducted with 2112 patients suffering COVID-19 infection. We built two sets of multivariate predictive models to assess the relationship between the long-term exposure to NO2 and PM10 and COVID-19 outcome. First, the probability of either death or severe COVID-19 outcome was predicted as a function of all the clinical variables together with the pollutants exposure by means of two regularized logistic regressions. Subsequently, two regularized linear regressions were constructed to predict the percentage of dead or severe patients. Finally, odds ratios and effects estimates were calculated. Results We found that the long-term exposure to PM10 is a more important variable than some already stated comorbidities (i.e.: COPD/Asthma, diabetes, obesity) in the prediction of COVID-19 severity and mortality. PM10 showed the highest effects estimates (1.65, 95% CI 1.32–2.06) on COVID-19 severity. For mortality, the highest effect estimates corresponded to age (3.59, 95% CI 2.94–4.40), followed by PM10 (2.37, 95% CI 1.71–3.32). Finally, an increase of 1 µg/m3 in PM10 concentration causes an increase of 3.06% (95% CI 1.11%-4.25%) of patients suffering COVID-19 as a severe disease and an increase of 2.68% (95% CI 0.53%-5.58%) of deaths. Discussion These results demonstrate that long-term PM10 burdens above WHO guidelines exacerbate COVID-19 health outcomes. Hence, WHO guidelines, the air quality standard established by the Directive 2008/50/EU, and that of the US-EPA should be updated accordingly to protect human health.

Over the last hundred years, life expectancy in developed countries has increased because of healthier living habits and the treatment of chronic pathologies causing premature aging. Aging is an inexorable, time-dependent, multifactorial process characterized by a series of progressive and irreversible physiological changes associated with loss of functional, psychological, and social capabilities. Numerous factors, such as oxidative stress, inflammation, and cellular senescence, and an irreversible geriatric syndrome known as frailty, contribute to human body deterioration in aging. The speed of aging may differ between individuals depending on the presence or absence of multiple factors (genetic and/or environment) and the subsequent misbalance of homeostasis, together with the increase of frailty, which also plays a key role in developing chronic diseases. In addition, pathological circumstances have been reported to precipitate or accelerate the aging process. This review investigated the mechanisms involved in the developing pathologies, particularly chronic kidney disease, associated with aging., Instituto de Salud Carlos III, Sociedad Española de Nefrología, Comunidad de Madrid, Fondo Social Europeo

Exposure of nanomaterials (NMs) to biological medium results in their direct interaction with biomolecules and the formation of a dynamic biomolecular layer known as the biomolecular corona. Despite numerous published data on nano-biointeractions, the role of protein glycosylation in the formation, characteristics, and fate of such nano-biocomplexes has been almost completely neglected, although most serum proteins are glycosylated. This study aimed to systematically investigate the differences in interaction of metallic NPs with glycosylated vs nonglycosylated transferrin. To reach this aim, we compared interaction mechanisms between differently sized, shaped, and surface-functionalized silver NMs and gold NMs to commercially available human transferrin (TRF), a glycosylated protein, and to its nonglycosylated recombinant form (ngTRF). Bovine serum albumin (BSA) was also included in the study for comparative purposes. Characterization of NMs was performed using transmission electron microscopy and dynamic and electrophoretic light scattering techniques. Fluorescence quenching and circular dichroism methods were used to evaluate protein binding constants on the nanosurface and conformational changes after the protein–NM interactions, respectively. Competitive binding of TRF, ngTRF, and BSA to the surface of different NMs was evaluated by separating them after extraction from protein corona by gel electrophoresis following quantification with a commercial protein assay. The results showed that the binding strength between NMs and transferrin and the changes in the secondary protein structure largely depend not only on NM physicochemical properties but also on the protein glycosylation status. Data gained by this study highlight the relevance of protein glycosylation for all future design, development, and efficacy and safety assessment of NMs., This study is based upon collaborative work from COST Action CA 17140 “Cancer Nanomedicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology). It was financially supported by the “Research Cooperability” Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014–2020 (grant HRZZ-PZS-2019-02-4323), Ministerio de Ciencia e Innovacion (Spain, grant BIO2017–84246-C2–1-R), Fondo Social de la DGA (grupos DGA), and Croatian Science Foundation (grant number HRZZ-IP-2016-06-2436). The authors would like to acknowledge the use of the Advanced Microscopy Laboratory (INMA-Universidad de Zaragoza) for access to their instrumentation and expertise.

A 60-year-old woman with primary hyperparathyroidism with previous nonconclusive imaging studies was referred for 18F-fluorocholine (18F-FCH) PET/CT as part of the preoperative diagnostic imaging workup to localize the adenoma before minimally invasive surgery. 18F-FCH PET/CT with dual time point was performed, acquiring immediately and 60 minutes after 18F-FCH administration. The early images demonstrated possible hyperfunctioning parathyroid tissue in the mediastinum, located in the right upper paratracheal space (region 2R), with an incidental iatrogenic subclavian venous air bubble embolism presenting as high uptake in the early images that disappeared in the late images. No symptomatology was reported during the examination.

Objective To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. Method Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. Results We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient = 0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32–2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001–1.063, P = .043). Conclusions Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the audiometric relapse-free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses.

The aim of this work is the development of highly protective agents to be administered locally within the middle ear to avoid cisplatin-induced ototoxicity, which affects to 100% of the clinical patients at ultra-high concentrations (16 mg/kg). The protective agents are based on polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate as anti-inflammarory and anti-apoptotic molecules. Dexamethasone and α-tocopheryl succinate are poorly soluble in water and present severe side effects when systemic administered during long periods of time. Their incorporation in the hydrophobic core of nanoparticles with the appropriate hydrodynamic properties provides the desired effects in vitro (lower cisplatin-induced toxicity, decreasing of caspase 3/7 activity, and lower IL-1β release) and in vivo (reducing the hearing loss at the local level). The local administration of the nanoparticles by bullostomy provides an adequate dose of drug without systemic interference with the chemotherapeutic effect of cisplatin. Statement of Significance 100% of the cancer patients receiving ultra-high doses of CDDP (16 mg/kg) suffer severe hearing loss, being a limiting factor in antineoplastic treatments. In this paper we describe the application of polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate to palliate the cisplatin ototoxicity derived from chemotherapy treatment. These new nanoparticles, that encapsulate, transport, and deliver dexamethasone or α-tocopheryl succinate in the middle ear, are able to partially prevent ototoxicity derived from high doses of CDDP. This is an interdisciplinary study in which in vitro and in vivo experiments are described and extensively discussed. The importance of the results opens an excellent opportunity to the translation to the clinic.

Background The word “re-laparotomy” defines the surgical procedure in which the abdominal cavity is re-explored to resolve the complications of the disease or initial surgery. Objective To determine the prevalence of abdominal re-operations in patients undergoing elective and emergency surgery in the General Hospital of Matamoros. Material and methods A retrospective, observational, longitudinal study was conducted by reviewing the medical records of patients with a re-operation from January 2014 to January 2015, statistically analysing the variables: age, sex, type of surgery, complications, and postoperative course. Results A total of 21 re-operated patients were found, the majority of whom were women (52.38%). The cases were more common in ages between 70 and 79 years old, in both sexes. Almost two-thirds (61.91%) of re-operations were after an emergency surgery. The residual abscess (23.8%) and evisceration (23.8%) were the most frequent indications for re-intervention. There were postoperative complications in 23.8%, with wound dehiscence (60%) being the most frequent. There was an 85.6% survival rate after the re-intervention. Conclusions The study showed a low incidence of re-interventions and a low mortality. There is evidence of major occurrence of abdominal re-interventions in advanced ages, in female patients, and emergency surgery.

We present an asymptomatic 70-year-old man referred for an 18F-FDG PET/CT for initial staging of a Hodgkin lymphoma. 18F-FDG PET/CT showed bilateral cervical lymphadenopathy (stage II). Incidentally, the CT demonstrated bilateral ground-glass opacities with low-grade 18F-FDG activity. CT findings were suspicious for COVID-19 pneumonitis. The COVID-19 reverse transcriptase polymerase chain reaction (RT-PCR) examination result was negative. Given the high clinical suspicion for COVID-19, the patient was isolated and repeat RT-PCR was positive at 72 hours. RT-PCR may be falsely negative in early COVID-19 disease, even with positive CT findings.

Aging is one of the hottest topics in biomedical research. Advances in research and medicine have helped to preserve human health, leading to an extension of life expectancy. However, the extension of life is an irreversible process that is accompanied by the development of aging-related conditions such as weakness, slower metabolism, and sti ness of vessels. It also debated that aging can be considered an actual disease with aging-derived comorbidities, including cancer or cardiovascular disease. Currently, cardiovascular disorders, including atherosclerosis, are considered as premature aging and represent the first causes of death in developed countries, accounting for 31% of annual deaths globally. Emerging evidence has identified hypoxia-inducible factor-1 as a critical transcription factor with an essential role in aging-related pathology, in particular, regulating cellular senescence associated with cardiovascular aging. In this review, we will focus on the regulation of senescence mediated by hypoxia-inducible factor-1 in age-related pathologies, with particular emphasis on the crosstalk between endothelial and vascular cells in age-associated atherosclerotic lesions. More specifically, we will focus on the characteristics and mechanisms by which cells within the vascular wall, including endothelial and vascular cells, achieve a senescent phenotype., Instituto de Salud Carlos III, Sociedad Española de Nefrología, Universidad de Alcalá, Grupo Santander, University of California San Diego

Metallodendrimers&mdash, dendrimers with included metals&mdash, are widely investigated as biocompatible equivalents to metal nanoparticles. Applications can be expected in the fields of catalysis, as chemical sensors in molecular recognition and as anticancer drugs. Metallodendrimers can also mimic certain biomolecules, for example, haemoprotein in the case of using a dendrimer with a porphyrin core. In previous papers, we showed the promising anticancer effects of carbosilane ruthenium dendrimers. The present paper is devoted to studying biocompatibility and the cytotoxic effect on normal and cancer cells of carbosilane ruthenium dendrimers labelled with fluorescent probe fluorescein isothiocyanate (FITC). The addition of fluorescent probe allowed tracking the metallodendrimer in both normal and cancer cells. It was found that carbosilane ruthenium dendrimer labelled with FITC in concentration up to 10 &micro, mol/L was more cytotoxic for cancer cells than for normal cells. Thus, FITC labelled carbosilane ruthenium dendrimer is a good candidate for diagnostic imaging and studying anticancer effects of metallodendrimers in cancer therapy.

Introduction Malignant external otitis is a necrotising infection, which extends from the squamous epithelium of the ear canal to the adjacent tissue. The objective of the study was to investigate its incidence and other epidemiological data in Spain, reporting the largest case series to date. Methods A descriptive, retrospective study of the Spanish population was carried out using the minimum basic data set (MBDS) based on data of patients admitted to hospitals in the 2008–2013 period. Patients whose diagnosis (principal or secondary) at discharge was encoded as 380.14 (malignant external otitis), according to ICD-9-CM, were included as cases. The Spanish incidence rate was calculated for all its communities and provinces, as well as by season and mortality. Results A total of 355 patients (302 as principal diagnosis and 53 as secondary) were diagnosed. The incidence rate was 1.30 (95% CI, 1.17–1.44) per 106 inhabitants and year, although there were variations among geographical areas. The median age of cases with main diagnosis was 74 years (range 10–95 years). The predominant age group was in patients over 84 years old (19.3 cases per 106 inhabitants and year). The incidence was higher in men and the male–female relative risk was 2.4. Diabetes was present in 74.6% of patients. The diagnosis was predominant in the last quarter of the year. The gross in-hospital mortality rate was 3.7%. Conclusions Malignant external otitis is seen mostly among male elderly and diabetic patients. The incidence and mortality rate are low in Spain.

Carlos Luna,1,* Matilde Alique,2,* Estefanía Navalmoral,2 Maria-Victoria Noci,3 Lourdes Bohorquez-Magro,2 Julia Carracedo,1 Rafael Ramírez2 1Nephrology Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; 2Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Madrid, Spain; 3Anesthesia Unit, Reina sofía University Hospital, Córdoba, Spain*These authors contributed equally tothis work Abstract: Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.Keywords: elderly, oxidative stress, microparticles, vascular damage

Backgrounds and purposes: Patients with chronic kidney disease (CKD) have higher risk of developing cardiovascular disease. In CKD patients the mechanisms involved in, endothelial damage and the role of different drugs used on these patients are not completely understood. The aim of this work is to analyze the effect of statins and platelet antiaggregant (PA) on endothelial microvesicles (EMVs) and other markers of endothelial dysfunction. Experimental approach: Cross-sectional study of 41 patients with CKD 3b-4 and 8 healthy volunteers. Circulating levels of EMVs, vascular endothelial growth factor (VEGF), and advance oxidized protein products (AOPPS) were quantified and the correlation with different comorbidity variables and therapeutic strategies were evaluated. Results: EMVs are increased in CKD patients as compared with controls (171.1 vs. 68.3/μl, p

Poor self-management by families is an important factor in explaining high rates of asthma morbidity in Puerto Rico, and for this reason we previously tested a family intervention called CALMA that was found effective in improving most asthma outcomes, but not effective in increasing the use of controller medications. CALMA-plus was developed to address this issue by adding to CALMA, components of provider training and screening for asthma in clinics.Study participants were selected from claims Medicaid data in San Juan, Puerto Rico. After screening, 404 children in eight clinics were selected after forming pairs of clinics and randomizing the clinics) to CALMA-only or CALMA-plus.For all three primary outcomes at 12 months, the mean differences between treatment arms were small but in the predicted direction. However, after adjusting for clinic variation, the study failed to demonstrate that the CALMA-plus intervention was more efficacious than the CALMA-only intervention for increasing controller medication use, or decreasing asthma symptoms. Both groups had lower rates of asthma symptoms and service utilization, consistent with previous results of the CALMA-only intervention.Compliance of providers with the intervention and training, small number of clinics available and the multiple barriers experienced by providers for medicating may have been related to the lack of difference observed between the groups. Future interventions should respond to the limitations of the present study design and provide more resources to providers that will increase provider participation in training and implementation of the intervention.

Carbamylation is a post-translational modification of proteins that may partake in the oxidative stress-associated cell damage, and its increment has been recently proposed as a “hallmark of aging”. The molecular mechanisms associated with aging are related to an increased release of free radicals. We have studied whether carbamylated proteins from the peripheral blood of healthy subjects are related to oxidative damage and aging, taking into account the gender and the immune profile of the subjects. The study was performed in healthy human volunteers. The detection of protein carbamylation and malondialdehyde (MDA) levels was evaluated using commercial kits. The immune profile was calculated using parameters of immune cell function. The results show that the individuals from the elderly group (60–79 years old) have increased carbamylated protein and MDA levels. When considered by gender, only men between 60 and 79 years old showed significantly increased carbamylated proteins and MDA levels. When those subjects were classified by their immune profile, the carbamylated protein levels were higher in those with an older immune profile. In conclusion, the carbamylation of proteins in peripheral blood is related to age-associated oxidative damage and to an aging functional immunological signature. Our results suggest that carbamylated proteins may play an important role at the cellular level in the aging process. post-print 1319 KB

Introduction Current schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient. Methods To determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5–2.5 mg/kg/day into two doses) for 1 year. The loss of 10 dB on two consecutive frequencies or 15 dB on an isolated frequency was considered as relapse. Results The mean age of the patients was 52.50 years (95% CI: 46.91–58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49 dB; DS 18.90) and PTA at 12 months (45.47 dB; DS 18.88) did not reach statistical significance (P=.799). There was a moderate positive correlation between female sex and the presence of systemic disease (R=.577). By applying Student's t for paired data, a significant difference (P=.042) was obtained between the PTA in frequencies up to 1000 Hz (PTA 125–1000 Hz). The relative incidence rate of relapse per year was .52 relapses/year (95% CI: .19–1.14]). The median time to audiometric relapse-free was 9.70 months (DS 1.03). Conclusions Azathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease.

Adolescents from Puerto Rican backgrounds are found to have higher rates of obesity than adolescents from other ethnic groups in the US. The objective of this study is to examine whether sleeping the recommended number of hours and depression or anxiety disorder are independently related to risk for obesity in a sample of Island Puerto Rican adolescents, and whether the association between sleep and obesity is moderated by depression or anxiety disorder. Data from the study were derived from the third wave of an island wide probability sample of Puerto Rican youth residing on the Island, 10–25 years of age (N = 825), with a response rate of 79.59%. The current study focuses on youth 10 to 19 years of age (n = 436). In this sample, youth who slept less than the recommended number of hours (defined as 7–9 h per night) had a significantly increased risk for obesity and were three times as likely to be obese. Youth who met criteria for a depressive/anxiety disorder were almost 2.5 times as likely to be obese. However, the presence of an anxiety/depressive disorders did not moderate the association between sleeping the recommended number of hours and risk for obesity. Sleeping less than the recommended number of hours may be an important risk factor for obesity status in Island Puerto Rican youth. These findings suggest that attention to healthy sleep behaviors and a sleep environment that promotes high quality sleep may be important for Puerto Rican adolescents at risk for obesity.

Persistent disparities in access and quality of mental health care for Latinos indicate a need for evidence-based, culturally adapted, and outside-the-clinic-walls treatments.Evaluate treatment effectiveness of telephone (ECLA-T) or face-to-face (ECLA-F) delivery of a 6-8 session cognitive behavioral therapy and care management intervention for low-income Latinos, as compared to usual care for depression.Multisite randomized controlled trial.Eight community health clinics in Boston, Massachusetts and San Juan, Puerto Rico.257 Latino patients recruited from primary care between May 2011 and September 2012.The primary outcome was severity of depression, assessed with the Patient Health Questionnaire-9 and the Hopkins Symptom Checklist-20. The secondary outcome was functioning over the previous 30 days, measured using the World Health Organization Disability Assessment Schedule (WHO-DAS 2.0).Both telephone and face-to-face versions of the Engagement and Counseling for Latinos (ECLA) were more effective than usual care. The effect sizes of both intervention conditions on Patient Health Questionnaire-9 were moderate when combined data from both sites are analyzed (0.56 and 0.64 for face-to-face and telephone, respectively). Similarly, effect sizes of ECLA-F and ECLA-T on the Hopkins Symptom Checklist were quite large in the Boston site (0.64 and 0.73. respectively) but not in Puerto Rico (0.10 and 0.03).The intervention appears to help Latino patients reduce depressive symptoms and improve functioning. Of particular importance is the higher treatment initiation for the telephone versus face-to-face intervention (89.7% vs. 78.8%), which suggests that telephone-based care may improve access and quality of care.

Renal dysfunction is closely associated with endothelial damage leading to cardiovascular disease. However, the extent to which endothelial damage induced by uremia is modulated by aging is poorly known. Aging can render endothelial cells more susceptible to apoptosis through an oxidative stress-dependent pathway. We examined whether senescence-associated to oxidative stress determines the injury induced by the uremia in endothelial cells. Human umbilical vein endothelial cells (HUVEC) was incubated with human uremic serum and, in the animal model, endothelial cells were obtained from aortas of uremic and no uremic rats. Vitamin C was used to prevent oxidative stress. Senescence, assessed by telomere length and enzyme-betagalactosidase (β-gal), reactive oxygen species (ROS), mitochondrial depolarization (JC-1 probe), caspase 3, and apoptosis were determined by flow cytometry. NF-κB activity was determined by Western blot. Uremic serum increased ROS and NF-κB in young and aging HUVEC. However only in aging cells, uremic serum induced apoptosis (vs young HUVEC, p

Objective To test the hypothesis that persons with the R230C allele of ABCA1 show a decreased glycemic response to glyburide. This polymorphism is exclusively found in Ameri-indian populations and is associated with type 2 diabetes. Research design and methods This is a single blind controlled study including participants with type 2 diabetes (fasting glucose levels 126-250 mg/dl and HbA1c 7%–10%) managed with metformin and a lifestyle program. Each person with the risk allele (R230C) was matched by age, gender and BMI to three others with the wild type variant (R230R). Following a four week stabilization period, only participants with a greater than 70% adherence to metformin and a stable body weight were prescribed glyburide therapy for a further 16 weeks. The main outcome variable was the glyburide dose required to achieve treatment goals. Results No significant difference was observed in the glucose lowering effect of glyburide between subjects with the R230C and R230R alleles. However, the dose of sulfonylurea was significantly higher in the R230C participants compared with the R230R subjects (3.3 ± 2.1 vs 6.3 ± 5 mg/day, p

Vascular calcification is commonly seen in elderly people, though it can also appear in middle-aged subjects affected by premature vascular aging. The aim of this work is to test the involvement of microvesicles (MVs) produced by senescent endothelial cells (EC) and from plasma of elderly people in vascular calcification. The present work shows that MVs produced by senescent cultured ECs, plus those found in the plasma of elderly subjects, promote calcification in vascular smooth muscle cells. Only MVs from senescent ECs, and from elderly subjects' plasma, induced calcification. This ability correlated with these types of MVs' carriage of: a) increased quantities of annexins (which might act as nucleation sites for calcification), b) increased quantities of bonemorphogenic protein, and c) larger Ca contents. The MVs of senescent, cultured ECs, and those present in the plasma of elderly subjects, promote vascular calcification. The present results provide mechanistic insights into the observed increase in vascular calcification-related diseases in the elderly, and in younger patients with premature vascular aging, paving the way towards novel therapeutic strategies., Instituto de Salud Carlos III, Red de Investigación Renal, Universidad de Alcalá, Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Fondos Feder European

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM. Support for this work was provided by Plan Nacional de IDi Proyectos de Investigación en Salud of Instituto de Salud Carlos III (ISCIII)–Subdirección General de Evaluación, Fondos de desarrollo regional (FEDER; PI11/01536, PI12/01489, PI14/00806, PI15/01785); Junta de Andalucía grants (P010-CTS-6337, P11-CTS-7352); and Fundación Nefrológica. P. Buendía, A. Carmona, and C. Luna-Ruiz are fellows from Consejería de Innovacion, Ciencia y Empresa, Junta de Andalucía.

Supplementary data to this article can be found online at http://dx.doi.org/10.1016/j.nano.2015.12.367., 6α-Methylprednisolone-loaded surfactant-free nanoparticles have been developed to palliate cisplatin ototoxicity. Nanoparticles were based on two different amphiphilic pseudo-block copolymers obtained by free radical polymerization and based on N-vinyl pyrrolidone and a methacrylic derivative of α-tocopheryl succinate or α-tocopherol. Copolymers formed spherical nanoparticles by nanoprecipitation in aqueous media that were able to encapsulate 6α-methylprednisolone in their inner core. The obtained nanovehicles were tested in vitro using HEI-OC1 cells and in vivo in a murine model. Unloaded nanoparticles were not able to significantly reduce the cisplatin ototoxicity. Loaded nanoparticles reduced cisplatin-ototoxicity in vitro being more active those based on the methacrylic derivative of vitamin E, due to their higher encapsulation efficiency. This formulation was able to protect hair cells in the base of the cochlea, having a positive effect in the highest frequencies tested in a murine model. A good correlation between the in vitro and the in vivo experiments was found., Authors acknowledge David Gómez, Rosa Ana Ramírez and Carlos Vargas for their help in SEM/TEM, cell culture and histology experiments, respectively. Authors also thank Dr. Kalinec for providing HEI-OC1 cells for the experiments

Objective:To evaluate patients with systemic lupus erythematosus and normal hearing over 10 years, compared with healthy controls.Methods:Thirty patients diagnosed with systemic lupus erythematosus were evaluated in a prospective, descriptive study. Eight patients fulfilled the inclusion criteria, i.e. normal otoscopy, normal hearing, normal imaging and disease duration of less than one year. Eleven healthy companions of ENT patients were recruited as controls.Results:At study commencement, the mean patient age was 32.75 years (range, 15–49 years) and there were no statistically significant audiometric differences between patients and controls. No statistically significant audiometric changes were found either within or between the patient and control groups at 10-year follow up.Conclusion:These results supply no evidence for progressive hearing loss in systemic lupus erythematosus patients with no hearing involvement at study commencement. Therefore, we recommend audiometric tests only for systemic lupus erythematosus patients complaining of hearing loss, or for other clinical purposes. It is conceivable that asymptomatic hearing loss could be observed over a more extended follow-up period (i.e. more than 10 years).

Lack of Klotho expression in mice leads to premature aging and age-related diseases, including vascular diseases. The aim of this study was to determine how endothelial cell line senescence affects Klotho expression and whether intra- or extracellular Klotho has any effect on the response of senescent cells to oxidative stress. The study was performed using human endothelial cells (HUVEC); cell aging was obtained by prolongation of cell division to 42 population doublings (PD). Senescence was also obtained by exposure to TNFα, which causes cell changes resembling cellular senescence. The decline in Klotho preceded the manifestations of cell ageing: telomere shortening and β-galactosidase expression. Klotho was also reduced in cells exposed to the proinflammatory cytokine TNFα. The addition of exogenous Klotho to aging cells did not modify the proportion of cells with short telomeres or any other feature of cell aging; however, exogenous Klotho prevented the changes resembling premature cellular senescence associated with TNFα, such as the decrease in telomere length and the increase in β-galactosidase-positive cells. Likewise exogenous Klotho prevented the increases in reactive oxygen species (ROS) activity, mitochondrial potential and cell apoptosis induced by TNFα.

Island Puerto Rican (PR) youth experience disproportionately high asthma and obesity rates compared with other racial/ethnic groups on the U.S. mainland. Previous research has demonstrated associations of chronic disease with psychiatric disorders.We examined the relationship among anxiety/depressive disorders, asthma, and obesity in an epidemiologic community sample of youth.The sample (n = 656) was derived from the second wave of an island-wide probabilistic representative household sample of PR youth stratified and based on whether or not they had a diagnosis of asthma and/or depressive/anxiety disorder. For this study, we used the subpopulation ages 10-19 years.Asthma and obesity were significantly related to higher odds of depressive/anxiety disorders in youth. Obesity moderated the relationship between asthma attacks and depressive/anxiety disorders. The relationship between asthma attack and higher odds for depressive/anxiety disorders was only present in the non-obese group. Among the obese, females show a significant increase from 11% to 36% in the prevalence of anxiety/depressive disorders. Asthma and obesity were highly prevalent and a significant association was found between asthma attack and depressive/anxiety disorders. The effects of asthma and obesity were not additive; the prevalence for psychiatric disorder for those having both conditions did not increase above the prevalence associated having only one of the conditions.Future studies should consider including longitudinal designs and examine the extent to which important variables not included in this study, such as body image dissatisfaction (particularly among females), teasing, and discrimination may moderate the relationship among obesity and depressive and anxiety disorders in youth.

Most of the natural cases of pneumonia in feedlot cattle are characterized by a longer clinical course due to chronic lung lesions. Microscopically, these lesions include interstitial fibroplasia, bronchitis, bronchiectasis, bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the aim was to review, under a medical perspective, the pathologic mechanisms operating in these chronic pneumonic lesions in calves. Based on the similarities of these changes to those reported in bronchiolitis obliterans/organising pneumonia (BO/OP) and chronic obstructive pulmonary disease (COPD) in human beings, calves are proposed as an alternative animal model.

This paper aims to study the effects of the oxidative stress induced by quality and quantity of dietary fat on cellular senescence. Twenty elderly subjects consumed three diets, each for 4 weeks: a saturated fatty acid diet (SFA), a low-fat and high-carbohydrate diet (CHO-ALA), and a Mediterranean diet (MedDiet) enriched in monounsaturated fatty acid following a randomized crossover design. For each diet, we investigated intracellular reactive oxidative species (ROS), cellular apoptosis and telomere length in human umbilical endothelial cells incubated with serum from each patient. MedDiet induced lower intracellular ROS production, cellular apoptosis, and percentage of cell with telomere shortening, compared with the baseline and with SFA and CHO-ALA diets. Dietary fat modulates the oxidative stress in human endothelial cells. MedDiet protects these cells from oxidative stress, prevents cellular senescence and reduces cellular apoptosis.

Carbamylated low-density lipoprotein (cLDL) plays a role in atherosclerosis. In this study we evaluate the effect of uremia on LDL carbamylation and the effect of cLDL and oxidized LDL (oxLDL; 200 μg/ml) on number, function, and genomic stability of endothelial progenitor cells (EPCs) obtained from healthy volunteers. cLDL was generated after incubation of native LDL (nLDL) with uremic serum from patients with chronic kidney disease (CKD) stages 2-4. Oxidative stress was measured by flow cytometry and fluorescent microscopy, mitochondrial depolarization by flow cytometry, senescence by β-galactosidase activity and telomere length, and DNA damage by phosphorylated histone H2AX (γH2AX). The percentage of cLDL by uremic serum was related to the severity of CKD. Compared with nLDL, cLDL induced an increase in oxidative stress (62±5 vs. 8±3%, P

Introduction Chronic inflammation of nasolacrimal duct determines obstruction of the lacrimal flow and is called chronic dacryocystitis. Endoscopic dacryocystorhinostomy (DCR) can solve this obstruction by opening the lacrimal sac directly to the nasal cavity, avoiding external scars in a simple, safe way. Material and method We reviewed all cases operated using this technique between January 1996 and June 2008. We focused on demographic characteristics as well as the results obtained (subjective and objective improvements). Results We reviewed 76 Endoscopic DCR that were performed during aforementioned period of time. Of these cases, 75% were females; mean age was 52.4 years old. Improvement in symptoms was reported by 80.3% of the patients. These data are similar to the results seen in other studies. Conclusions Endoscopic dacryocystorhinostomy is a simple, safe technique for treating chronic dacryocystitis, which provides similar or even better rates of improvement than other techniques used for this condition. In our patients, the results are not different from those observed in other studies. Our outcomes are comparable to those observed in other studies.

This study examined whether perceived discrimination was related to antisocial behaviors (ASB) in a probability sample of Puerto Rican children living in the South Bronx, New York and the San Juan Metropolitan area of Puerto Rico (N = 1,271). After adjusting for a host of well-known factors associated with ASB, such as sociodemographic variables (i.e., age, gender, household composition), psychosocial stressors (i.e., stressful life events, exposure to violence), and various forms of violence and abuse (i.e., coercive parental discipline, verbal, psychological, physical and sexual abuse), perceived discrimination remained a robust correlate of ASB among both samples. Findings are discussed with reference to the detrimental associations of perceived discrimination.

Disparities exist in asthma medication dispensing between children with public insurance and those with private insurance under a Managed Care Medicaid system in Puerto Rico.Island-wide medical claims data were used to examine the extent to which differences between the private and public health care sectors affect medication dispensing and health care utilization among asthmatic children.Children 3-18 years old with at least one service claim [outpatient, hospitalization, or emergency department (ED) visit] for asthma or reactive airway disease from 2005 to 2006 were selected. Chi-square analyses compared medication dispensing and health care utilization between the public and private sectors. Negative binomial regression identified factors associated with the mean dispensing rate of prescriptions for anti-inflammatory controller medication (CM).Private insurance families (n = 28,088) were dispensed significantly more CM (48.3% vs. 12.0%) and quick relief medication (47.4% vs. 44.6%) than public insurance families (n = 13,220). The dispensing of inhaled corticosteroids (24.4% vs. 6.7%) and leukotriene modifiers and cromolyn (31.4% vs. 5.7%) was dramatically higher in the private sector. In contrast, emergency room use was significantly higher among public insurance children (51.7% vs. 13.8%). Multivariate analysis showed that age, number of β-agonists, and type of insurance was associated with CM dispensing; private insurance showed the greatest effect.Asthmatic Puerto Rican children enrolled in public insurance were significantly less likely to be dispensed CM than children with private insurance; suggesting that under-treatment of public insured children may substantially contribute to increased asthma morbidity in this population as evidenced by significantly higher rates of ED visits.A disparity exists in asthma medication dispensing between children with public insurance compared with those with private insurance under a Managed Care Medicaid system in Puerto Rico. If asthma disparities in medication dispensing are to be reduced, then a better understanding of the complex ways in which multiple variables related to the health care system policies, socioeconomic factors, family and provider interactions, as well as the relative weight that each one contributes to the observed inequalities is needed.

Algal infections are rare in humans and domestic animals. Prototheca spp. and Chlorella spp. are among the most commonly reported. Herein, we present a brief review on Chlorella spp. infections and related pathologies and discuss this information including a natural case in a sheep in Mexico with a disseminated form of the disease.

Many patients with otological symptoms are remitted to the otolaryngology outpatient clinics every day. These patients commonly undergo imaging studies, generally magnetic resonance imaging (MRI). In some cases, a positive unilateral result is found in the form of a potentially pathological signal that can be observed in the petrous apex region. We present the cases of 6 patients (aged between 26 and 62 years) with asymmetric bone marrow distribution or trapped mucous fluid secretions in the petrous apex, collected over a 6-year period. Diagnosis was made with the use of CT scans and MRI. All of the patients were referred for skull base surgery. In all cases a non-pathologic asymmetry was diagnosed in the petrous apex. Certain non-pathologic conditions of the petrous apex must be treated expectantly without any surgery.

Context and objectiveAdipokines are involved in the etiopathology of obesity-related disorders. Since the role of adipokine retinol-binding protein-4 (RBP4) in obesity remains uncertain and its relationship with other adipokines and inflammatory markers has not been examined in detail, we investigated the relationships of RBP4 mRNA expression and circulating protein levels with obesity, anthropometric and metabolic variables, as well as with obesity-related inflammatory markers adiponectin and C-reactive protein.Subjects and methodsOne-hundred and twenty-five subjects participated, 36 lean (body mass index (BMI): 2) and 89 obese (overweight/obese; BMI: ≥25ResultsThere was a tendency for circulating RBP4 levels to positively correlate with waist circumference (β=0.29, P=0.08; R2=0.08), but there was no significant association with the obesity-related parameters analysed. RBP4 and adiponectin mRNA expression levels were similarly downregulated in the s.c.-AT of obese subjects (0.5-fold); however, RBP4 downregulation did not affect its circulating protein levels. The expression of RBP4 and adiponectin was positively correlated even after controlling for confounding factors (β=0.59, PR2=0.40).ConclusionsIn our population, RBP4 circulating levels were not significantly correlated with obesity-related parameters, although a tendency to correlate with waist circumference suggests a relationship with insulin resistance and other metabolic disorders. In addition, our results suggest that the production of RBP4 by other tissues such as liver, rather than s.c.-AT, may be involved in regulating RBP4 circulating levels.

Viral infections of the labyrinth have been considered a major source of auditory and vestibular system pathology. However, the involvement of virus in the development of immune reactions responsible for immunomediated inner ear disease has not been studied enough. Following viral infection, an effector immune response, humoral (B cell) and/or cytotoxic (T cell) is directed against a virus and it might cross-react with self-protein or autoantigen, evoking an autoimmune response. Since clinically it can be very difficult to establish a viral etiology for such disorders, serologic studies can be used to confirm the suspected diagnosis. Patients affected by immunomediated inner ear disease that had presented an upper respiratory tract infection underwent an immunologic workup study including microbiological study. After the application of this diagnostic protocol, only one patient, that was subsequently diagnosed with Cogan’s syndrome, showed a positive serological test for viral infection. On the basis of the low efficacy of serological testing and due to the lack of evidence, we do not recommend to carry out serologic studies for viral infection.

Background: Because of their anti-inflammatory effects and suppression of the immune system, glucocorticoids have been widely used in otolaryngologic disorders and perioperative conditions. Objective: The objective of the present study was to determine the incidence of adverse effects after the administration of glucocorticosteroids in patients affected by diverse inner ear disorders. Methods: One hundred and sixty-three patients affected by sudden sensorineural hearing loss, 39 with progressive sensorineural hearing loss and 16 with fluctuating sensorineural hearing loss were subjected to glucocorticosteroid therapy with 6-methylprednisolone at a starting dose of 1 mg/kg body weight per day; this therapy was tapered during the next 21–28 days. In 20 patients with profound hearing loss (>70 dB), 3 boluses of prednisolone-21-hydrogen-succinate (500 mg per day) were administered. After receiving the boluses, these patients continued with the oral 6-methylprednisolone scheme. Results: Mild adverse effects were observed in 16 patients (7.01%). Only 2 patients (0.9%) with sudden sensorineural hearing loss showed severe complications: peptic ulcer and avascular necrosis of the femoral heads. Conclusions: The low percentage of severe adverse effects observed in the present study validates the use of corticosteroids for the treatment of inner ear disorders although we should not underestimate these rare complications.

Schwannomas (or neurilemmomas) are slow-growing mesenchymal neoplasms of the peripheral nerve sheath that may arise at almost any anatomical site. Mesentery schwannoma is extremely rare, with less than ten previously described cases. We present the case of a 38-year-old woman with arterial hypertension and chronic kidney disease with an abdominal painless mass of two years duration and an inconclusive pre-operative clinical diagnosis; she was successfully treated by complete surgical resection of the mass. The aim of this report is to recognize the possibility of schwannomas in the differential diagnosis of abdominal slowly growing tumors.

Background: Research comparing treatment-referred boys and girls with attention-deficit/hyperactivity disorder (ADHD) has yielded equivocal results. Contradictory findings may be associated with differential referral practices or unexplored interactions of gender with ADHD subtypes. Method: We examined possible gender differences in ADHD and its subtypes among children aged 4 to 17 in a representative community sample (N ¼ 1896) in Puerto Rico. Caretakers provided information through the Diagnostic Interview Schedule for Children (version IV) and a battery of impairment, family relations, child problems, comorbidity and treatment measures. Results: ADHD was 2.3 times more common in boys than girls, but with one exception there was little evidence that the patterns of associations of ADHD with correlates were different for boys and girls. The exception was school suspension, which was more common among ADHD boys than girls. Additional gender interactions were found when ADHD subtypes were considered. Among those with combined type (n ¼ 50), boys were more likely to be comorbid with mood disorders than girls. For those with the inattentive type (n ¼ 47), girls were more likely to be comorbid with anxiety disorders than boys. Conclusions: Our findings lend cross-cultural generalizability to recent reports that gender does not interact with correlates for ADHD overall, but that it may play a role in subtypes. Keywords: Attention deficit/hyperactivity impulsivity disorder, gender differences, Latino/Hispanics, ADHD subtypes. Abbreviations: CT: combined type; HIT: hyperactiveimpulsive type; IT: predominantly inattentive type; ICC: intraclass correlation coefficient. The research literature on attention-deficit/hyperactivity disorder (ADHD) reports that individuals with this disorder present diverse family backgrounds, patterns of comorbidity, and impairment profiles. The heterogeneous nature of ADHD has led to its subdivision into more homogeneous subtypes based on the predominance of symptoms of inattention (predominantly inattentive subtype or IT), of hyperactivity-impulsivity symptoms (hyperactiveimpulsive subtype or HIT) or on both sets of symptoms (combined subtype or CT) (American Psychiatric Association, 1994). Research has generally supported the validity of the DSM-IV subtypes (e.g., Carlson, Shin, & Booth, 1999; Bauermeister et al., 2005; Graetz, Sawyer, Hazell, Arney, & Baghurst, 2001). The CT and IT may be stable enough over time to segregate groups for research (Lahey, Pelham, Loney, Lee, & Willcutt, 2005).

Cardiovascular complications are a major cause of mortality in hemodialysis patients. On-line hemofiltration combines convective clearance for removing large solutes with diffusion to remove small solutes and is associated with a significant reduction of inflammation and improved patient survival. We compared on-line hemofiltration to high-flux hemodialysis (HF-HD) in patients in a sequential manner. At baseline, 15 stable patients on HF-HD as compared with five control subjects showed significant increases in CD14+CD16+ cells, endothelial microparticles, and endothelial progenitor cells (EPCs). After 4 months of on-line hemofiltration, the number of CD14+CD16+ cells, microparticles, and EPCs decreased. After returning to HF-HD for 4 months, all measured parameters returned to their respective baseline values. The number of CD14+CD16+ cells correlated with both endothelial microparticles and EPCs. We conclude that on-line hemofiltration attenuates endothelial dysfunction possibly by decreasing microinflammation. This effect may be directly caused by a modulatory effect of on-line hemofiltration on proinflammatory cells or by a complex interaction that encompasses a wider removal of uremic toxins.

Objective: We examined the prevalence of smoking behaviors and their association with specific psychiatric disorders in a representative sample of youth from behavioral health clinics in Puerto Rico. Method: A complex sampling design was used to select the sample, and analyses were conducted to account for the unequal selection probability, stratification, and clustering. All analyses were weighted back to the clinical population from which they were drawn. Psychiatric and substance use disorders were assessed using the parent and youth versions of the Diagnostic Interview Schedule for Children, Version 4.0. Results: More than one third of the sample reported experience with cigarette smoking, and approximately one quarter reported smoking at least once per week (23.4%). As expected, the alcohol and drug use disorders demonstrated some of the strongest associations with individual smoking stages. These were the only disorders that remained significantly associated with nicotine dependence after controlling for comorbidity. Conclusions: Our findings confirm the need for screening of smoking behavior and nicotine dependence in treatment settings and the integration of psychiatric/substance use treatments with smoking cessation.

Resumen La Sociedad Española de Nefrología elaboró en 2004 una Guía de Gestión de Calidad del Líquido de Diálisis. La segunda edición revisada de la guía ha tenido en cuenta nuevas evidencias y la normativa internacional. En la guía se hacen algunas recomendaciones sobre normas para preparar el líquido de diálisis: agua, concentrados y sistemas de dosificación de la hemodiálisis. Esta guía se basa en la norma ISO13959, la Farmacopea Europea, la Real Farmacopea Española, las normas y prácticas recomendadas de la AAMI, la Guía Europea de Buena Práctica en Hemodiálisis, revisiones de la bibliografía, según su nivel de evidencia, y la opinión del grupo español de expertos. Se definieron 2 niveles de calidad del agua: agua purificada y agua purificada de alta calidad (ultra pura), y para el líquido de diálisis: líquido de diálisis ultra puro. El uso habitual de líquido de diálisis ultra puro se recomienda en todo tipo de hemodiálisis para prevenir y retrasar la aparición de complicaciones: inflamación, desnutrición, anemia y amiloidosis. Los requisitos de la calidad del agua, de los concentrados y del líquido de diálisis se definen como los niveles máximos admisibles de contaminantes: sustancias químicas (4.1.2), conductividad, microbiana y endotoxinas (4.1.1): Microbiana (UFC/ml) Endotoxinas prueba LAL (UE/ml) Agua purificada ≤ 100 UFC/ml ≤ 0,25 Agua ultra pura ≤ 10 UFC/100 ml ≤ 0,03 Líquido de diálisis ultra puro ≤ 10 UFC/100 ml ≤ 0,03 Se especificaron la frecuencia de control, el mantenimiento y las medidas correctivas. Los métodos de muestreo y análisis se describieron en los anexos. Para el control microbiológico es recomendable el medio de cultivo R2A, incubado durante 7-14 días a una temperatura de 17-23 °C. El proceso de garantía de la calidad del líquido de diálisis implica a todos los miembros del personal de diálisis y exige protocolos estrictos. El médico a cargo de la hemodiálisis tiene la responsabilidad final de la calidad del líquido de diálisis. Pueden dirigir sus sugerencias y preguntas acerca de esta guía a www.senefro.org. Abstract A Best Practice Guideline about Dialysis fluid purity was developed under the leadership of the Spanish Society of Nephrology in 2004. The second edition revised Guideline considered new evidences and International Standard. The Guideline has established recommendations for standards for preparing dialysate: water, concentrates and hemodialysis proportioning systems. This Guideline is based on the ISO13959, European Pharmacopoeia, the Real Farmacopea Española, the AAMI Standards and Recommended Practices, European Best Practice Guidelines for Haemodialysis, literature reviews, according to their level of evidence, and the opinion of the expert Spanish group. Two levels of quality of water were defined: purified water and high purified water (ultra pure) and for dialysate: ultra pure dialysate. Regular use of ultra pure dialysate is recommended for all type of hemodialysis to prevent and delay the occurrence of complications: inflammation, malnutrition, anaemia and amiloidosis. Water, concentrates and dialysate quality requirements are defined as maximum allowable contaminant levels: chemicals (4.1.2), conductivity, microbial and endotoxins (4.1.1): Microbial (CFU/ml) Endotoxins LAL test (EU/ml) Purified water ≤ 100 CFU/ml ≤ 0,25 High purified water ≤ 10 CFU/100 ml ≤ 0,03 Ultra pure dialysate ≤ 10 CFU/100 ml ≤ 0,03 Monitoring frequency, maintenance and corrective actions were specified. Methods of sampling and analysis were described in appendix (anexos). For microbiological monitoring, R2A medium is recommended, incubated during 7-14 days at a temperature of 17-23 °C. The dialysate quality assurance process involves all dialysis staff members and requires strict protocols. The physician in charge of hemodialysis has the ultimate responsibility for dialysate quality. All suggestions and questions about this Guideline are wellcome to www.senefro.org.

Hemodiafiltration with endogenous reinfusion (HFR) after ultrafiltrate passage through a resin cartridge combines adsorption, convection, and diffusion. Our prospective single-center crossover study compared HFR and online-hemodiafiltration (OLHDF) effects on two uremic toxins and 13 inflammatory, endothelial status, or oxidative stress markers. After an 8-week run-in period of high-flux hemodialysis, 17 eligible stable dialysis patients (median age 65 years, 10 male) without overt clinical inflammation were scheduled for four 8-week periods in the sequence: HFR/OLHDF/HFR/OLHDF. Relative to OLHDF, HFR was associated with greater indoxyl sulfate removal and lesser abnormalities in all other study variables, namely circulating interleukin-6, tumor necrosis factor-alpha, proportions of activated proinflammatory (CD14+CD16+, CD14++CD16+) monocytes, endothelial progenitor cells, apoptotic endothelial microparticles, vascular endothelial growth factor, vascular cellular adhesion molecule, angiopoietins 2 and 1, annexin V, and superoxide dismutase. Differences were significant (P 0.05) in median values of 13/15 variables. Study period comparisons were generally consistent with dialysis technique comparisons, as were data from the subgroup completing all study periods (n = 9). Our investigation provides hypothesis-generating results suggesting that compared with OLHDF, HFR improves protein-bound toxin removal, inflammatory and endothelial status, and oxidative stress.

It is not known whether high convective transport may have a role in modulating the chronic inflammation of hemodialysis (HD) patients. The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on proinflammatory peripheral monocytes: Percentage of CD14+CD16+ cells and their telomere length and spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6). In a prospective, crossover study, 31 patients who were on high-flux HD (HF-HD) were evaluated. Patients underwent the following sequence of treatments (4 mo each): HF-HD (basal), OL-HDF (period 1), HF-HD (period 2), OL-HDF (period 3), and HF-HD (period 4). The dialysis characteristics were similar in the two modalities; the only difference was a higher convective transport in the OL-HDF than in the HF-HD. All patients who were on OL-HDF periods showed a significantly lower number of CD14+CD16+ cells than on HF-HD (18.5 +/- 2.3 basal versus 13.6 +/- 2.9 period 1 and 13.9 +/- 2.3 period 3; P = 0.001). By contrast, HF-HD restored the number of CD14+CD16+ cells to the basal values (19.2 +/- 2.8 and 18.6 +/- 1.4, periods 2 and 4, respectively; NS). During OL-HDF periods, the reduction of CD14+CD16+ was paralleled by a decreased number of short telomere cells. Spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6) was increased in HF-HD as compared with OL-HDF. In conclusion, these results demonstrate that as compared with HF-HD, OL-HDF markedly reduces the number of proinflammatory CD14+CD16+ cells and the production of TNF-alpha and IL-6. Future studies are needed to assess the possible therapeutic effect of convective transport on chronic inflammation that is associated with HD.