Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression.

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1ß, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients' plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.

Functionally aligned total knee arthroplasty: A lateral flexion laxity up to 6 mm is safe!

PURPOSE: Loose flexion gaps are associated with poor functional outcomes and instability in total knee arthroplasty (TKA). The effect of a trapezoidal flexion gap in a functionally aligned TKA remains unknown. The aim of this study was to investigate the effect of a larger lateral flexion gap in a robotic-assisted (RA), functionally aligned (FA) and cruciate-retaining (CR) TKA on clinical outcomes. METHODS: Data from 527 TKA in 478 patients from 2018 to 2020 were collected. All patients underwent an RA (MAKO, Stryker), FA and CR TKA. Gap measurements were collected intraoperatively. Patient-reported outcome measures (PROMs), pain Visual analogue score (VAS) and range of motion were collected postoperatively. Patients were also asked about the ease of stair ascent and descent and kneeling on a 5-point scale. The minimum follow-up was 2 years. Patients were stratified into three groups based on lateral flexion laxity. RESULTS: At 2 years postoperatively, the group with a looser gap (3-6 mm) had higher mean PROMs when compared with the group with a gap of 2-3 mm. There were no differences detected in any other outcomes at 2 years. A total of 70.9% of patients in the group with a 3-6 mm gap reported being able to walk down a flight of stairs 'easily', compared with 56.7% in the 2-3 mm group and 54% in the <2 mm group (p = 0.04). CONCLUSION: The study shows that a loose lateral flexion gap in functionally aligned CR TKA does not adversely affect outcomes in the short term. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

A framework for the systematic evaluation of a novel cigarette filter technology.

Any functional change in cigarette filter design warrants a rigorous assessment to ensure comparability to existing filter functionality. This study compares the functionality of a standard CA filter with a novel cellulose-based alternative using a combination of emissions, in silico approaches, pre-clinical assessments and behavioural studies. We assess the challenges faced with a significant filtration change, the substantiation of this change and the limitations of such assessments. We explore cigarette emission chemical profiles; assess the potential toxicological impacts (in vitro and statistical modelling) of the differing chemical profiles of cigarette smoke aerosol resulting from the respective filter types; and, finally investigate the behavioural aspects associated with use of the novel filter as compared to the traditional one. The aim of the study was to establish a weight of evidence assessment framework for the comprehensive evaluation of a novel cigarette filter design as part of robust stewardship approach. The data show comparability to a standard CA filter across all assessments and highlight potential areas of investigation for future novel filter product iterations. The approach demonstrates the applicability of a comprehensive step-wise assessment framework to identify any potential increased toxicant emissions and exposures associated with using the novel filter.

Behavioural intention of hand hygiene compliance in an average Ecuadorian hospital.

OBJECTIVE: This study aimed to characterize hand hygiene behavioural intention by hospital services clusters in a medium-sized hospital in an Ecuadorian city. METHODS: This is a cross-sectional study based on the World Health Organization Hand Hygiene Knowledge Questionnaire for Health-Care Workers. The responses on hand hygiene behavioural intention for the Five Moments for hand hygiene according to the World Health Organization were recorded in three categories: before patient contact, before and after sterile technique and management of body fluids, and after contact with the environment of the patient. The variables were the knowledge regarding the source of germs causing nosocomial infections, the optimal time to achieve disinfection with alcohol, hospital services clusters (clinical medicine, surgery, and therapeutic services), and history of previous formal hand hygiene training. The variables in each moment were analysed using a saturated log-linear model. RESULTS: The average age of participants was 34 years (Q1 32.1-Q3 36.4). Of them, 62% belonged to the clinic cluster and 87.6% had previous formal hand hygiene training. The incorrect response rates for before and after sterile technique and management of body fluids, before patient contact, and after contact with the environment of the patient were 30.2, 88.4, and 99.2%, respectively. In before patient contact, the incorrect responses for optimal time depended on the department (worse surgery cluster situation), and in before and after sterile technique and management of body fluids and after contact with the environment of the patient, the incorrect responses for source of germs depended on the previous formal hand hygiene training and the department (worse surgery and clinic clusters). CONCLUSION: The incorrect answer related to hand hygiene behavioural intention was high compared to other reports, and the worse situation was found in after contact with the environment of the patient and before patient contact. These data suggest the need of strengthening permanently the hand hygiene programme.

Behavioural intention of hand hygiene compliance in an average Ecuadorian hospital

SUMMARY OBJECTIVE: This study aimed to characterize hand hygiene behavioural intention by hospital services clusters in a medium-sized hospital in an Ecuadorian city. METHODS: This is a cross-sectional study based on the World Health Organization Hand Hygiene Knowledge Questionnaire for Health-Care Workers. The responses on hand hygiene behavioural intention for the Five Moments for hand hygiene according to the World Health Organization were recorded in three categories: before patient contact, before and after sterile technique and management of body fluids, and after contact with the environment of the patient. The variables were the knowledge regarding the source of germs causing nosocomial infections, the optimal time to achieve disinfection with alcohol, hospital services clusters (clinical medicine, surgery, and therapeutic services), and history of previous formal hand hygiene training. The variables in each moment were analysed using a saturated log-linear model. RESULTS: The average age of participants was 34 years (Q1 32.1-Q3 36.4). Of them, 62% belonged to the clinic cluster and 87.6% had previous formal hand hygiene training. The incorrect response rates for before and after sterile technique and management of body fluids, before patient contact, and after contact with the environment of the patient were 30.2, 88.4, and 99.2%, respectively. In before patient contact, the incorrect responses for optimal time depended on the department (worse surgery cluster situation), and in before and after sterile technique and management of body fluids and after contact with the environment of the patient, the incorrect responses for source of germs depended on the previous formal hand hygiene training and the department (worse surgery and clinic clusters). CONCLUSION: The incorrect answer related to hand hygiene behavioural intention was high compared to other reports, and the worse situation was found in after contact with the environment of the patient and before patient contact. These data suggest the need of strengthening permanently the hand hygiene programme.

Twelve weeks of water-based circuit training exercise improves fitness, body fat and leg strength in people with stable coronary heart disease: a randomised trial.

QUESTION: In people with stable coronary heart disease, what are the effects of water-based circuit training exercise on aerobic capacity, strength and body composition? How do these effects compare with those of gym-based exercise? DESIGN: Parallel group, randomised controlled trial with concealed allocation and intention-to-treat analysis. PARTICIPANTS: Fifty-two participants with stable coronary heart disease. INTERVENTIONS: Twelve weeks of: three 1-hour sessions per week of moderate-intensity water-based circuit training exercise with alternating aerobic and resistance stations (WEX); three 1-hour sessions per week of moderate-intensity gym-based circuit training exercise (GEX); or continuing usual activities (control). OUTCOME MEASURES: Aerobic capacity (VO2peak), upper and lower limb one repetition maximum strength (biceps curl, latissimus dorsi pulldown, hamstring curl and leg press), anthropometry (weight, body mass index and girth) and dual energy x-ray absorptiometry. RESULTS: Forty-five participants completed the study (WEX n = 15, GEX n = 18, control n = 12). Both training groups significantly improved VO2peak compared with control: WEX by 2.5 ml/kg/min (95% CI 0.6 to 4.4) and GEX by 2.3 ml/kg/min (95% CI 0.6 to 4.0). WEX and GEX improved hamstring strength compared with control: WEX by 6.3 kg (95% CI 1.2 to 11.3) and GEX by 7.6 kg (95% CI 2.9 to 12.2). Compared with control, GEX increased leg press strength by 15.5 kg (95% CI 5.7 to 25.3), whereas the effect of WEX was less clear (MD 7.1 kg, 95% CI -3.5 to 17.7). Only GEX improved latissimus dorsi pulldown strength. Compared with control, total body fat was reduced with WEX (-1.1 kg, 95% CI -2.3 to 0.0) and GEX (-1.2 kg, 95% CI -2.3 to -0.1). There were negligible between-group differences in weight or waist circumference. CONCLUSION: WEX was well tolerated and improved aerobic capacity, leg strength and body fat to a similar degree as GEX in people with coronary heart disease. These findings suggest that WEX is an effective exercise training alternative to GEX for people with coronary heart disease. TRIAL REGISTRATION: ANZCTR12616000102471.

Peroral endoscopic myotomy as treatment for Zenker's diverticulum (Z-POEM): a multi-center international study.

BACKGROUND: Peroral endoscopic myotomy for the treatment of Zenker's diverticulum (Z-POEM) is a novel technique that has been described in several recent reports. This method utilizes the third space (submucosal layer) to create a tunnel to facilitate complete visualization of the septum and hence cutting it entirely. Conventional endoscopic septotomy carries the risk of recurrence due to incomplete visualization of the septum. While surgical correction is a risky and lengthy procedure in old comorbid patients with Zenker's diverticulum. The aim of this study is to assess the efficacy and safety of Z-POEM. METHODS: The study enrolled 24 patients diagnosed with Zenker's diverticulum (ZD) who underwent Z-POEM at seven independent endoscopy centers in five different countries. RESULTS: Mean patient age ± standard deviation (SD) was 74.3 ± 11 years. Most of the patients were males (n = 20, 83.3%); four (16.7%) were females. More than 50% of the patients (n = 14, 58.3%) had associated comorbidities. The mean size of the diverticula was 4 cm (range 2-7 cm). The Kothari-Haber Score was used to assess clinical symptoms; values ranged from 6 to 14 (median = 9). We achieved 100% technical success with a median procedure time of 61 min and no adverse events. Median hospital stay was 1 day (range 1-5 days). There is a significant reduction in the Kothari-Haber Score after Z-POEM (P < 0.0001). Technical success was achieved in 100% of the patients. Clinical success was achieved in 23/24 (95.8%) of the patients with a median follow-up of 10 months (range 6-24 months). CONCLUSION: Z-POEM is a safe and effective modality for managing ZD.

High-intensity interval training in patients with left ventricular assist devices: A pilot randomized controlled trial.

BACKGROUND: Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure. To date, studies evaluating the impact of aerobic training in patients with LVADs have focused on moderate-intensity exercise. METHODS: This pilot randomized controlled trial compared the effects of high-intensity interval training (HIIT) with those of moderate-intensity continuous training (MICT) on peak oxygen consumption (V̇O2 peak) in patients with LVADs. Secondary outcomes included 6-minute walk test distance, flow-mediated dilation, and anthropometry. Assessments were conducted at baseline and after 12 weeks of supervised training performed 3 times weekly. Participants were randomized to HIIT (4 sets of 4 minutes at 80%-90% V̇O2 reserve, alternating with 3 minutes at 50%-60% V̇O2 reserve) or MICT groups (28 minutes continuously at 50%-60% V̇O2 reserve). Within and between-group differences were analyzed using linear mixed models. Data are expressed as marginal means with 95% confidence intervals or as mean ± SD. RESULTS: A total of 21 participants were randomized (HIIT: age 57.7 ± 13.1 years; n = 11 and MICT: age 55.6 ± 14.2 years; n = 10) (mean ± SD). No major adverse events occurred in response to training in either group. HIIT significantly improved V̇O2 peak (15.6 [13.2-17.8] to 18.4 [16.0-20.8] ml/kg/min) (marginal mean [95% CI]) compared with MICT (16.2 [13.8-18.7] to 17.2 [14.6-19.7] ml/kg/min; p < 0.05 between groups). No significant group differences were detected in secondary outcomes. CONCLUSION: In patients with LVADs, HIIT was well tolerated and increased aerobic capacity more than MICT. These preliminary findings support the prescription of high-intensity exercise in clinically stable patients with LVADs but warrant validation in a larger sample and across a broader range of physiologic and clinical outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au, unique identifier: ACTRN12616001596493.

Physical Activity Is Higher in Patients with Left Ventricular Assist Device Compared with Chronic Heart Failure.

PURPOSE: Left ventricular assist devices (LVAD) are associated with an increased aerobic capacity in patients with chronic heart failure (CHF). However, studies evaluating the impact of LVAD implantation on physical activity (PA) are lacking. The aim of this study was to compare daily PA levels in participants with LVAD with well-matched CHF participants. METHODS: Sixteen participants with an LVAD (age, 59.1 ± 10.8 yr) were case-matched to 16 participants with advanced CHF (age, 58.3 ± 8.7 yr), who were listed or being considered for cardiac transplantation. Participants underwent a cardiopulmonary exercise test to determine peak oxygen consumption (V˙O2 peak). Physical activity was monitored continuously for seven consecutive days with an Actiheart monitor. RESULTS: V˙O2 peak in the CHF group (12.3 ± 3.5 mL·kg·min) was not significantly different to the LVAD group before LVAD implantation (10.4 ± 2.1 mL·kg·min), but was lower than in the LVAD group after implantation (15.8 ± 4.3 mL·kg·min; P < 0.05). Physical activity was higher in the LVAD (19.7 ± 6.4 kJ·kg·d) compared with the CHF group (11.6 ± 6.9 kJ·kg·d; P = 0.001). The LVAD participants spent more time performing moderate-intensity PA than their CHF counterparts (median, 26 min·d; interquartile range, 24-40 min·d vs median, 12 min·d; interquartile range, 9-16 min·d; P < 0.001). Physical activity was correlated with V˙O2 peak (r = 0.582; P = 0.001) across participants in the CHF and LVAD groups. CONCLUSIONS: Higher levels of PA were observed in participants with LVAD compared with patients with advanced CHF. This may be due to a higher V˙O2 peak, resulting in an improved capacity to perform activities of daily living with less symptoms.

Cerebral blood flow responses to exercise are enhanced in left ventricular assist device patients after an exercise rehabilitation program.

Cerebral blood flow during exercise is impaired in patients with heart failure implanted with left ventricular assist devices (LVADs). Our aim was to determine whether a 3-mo exercise training program could mitigate cerebrovascular dysfunction. Internal carotid artery (ICA) blood flow and intracranial middle (MCAv) and posterior cerebral (PCAv) artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental cycle ergometer exercise protocol in 12 LVAD participants (5 female, 53.6 ± 11.8 yr; 84.2 ± 15.7 kg; 1.73 ± 0.08) pre- (PreTR) and post- (PostTR) completion of a 3-mo supervised exercise rehabilitation program. At rest, only PCAv was different PostTR (38.1 ± 10.4 cm/s) compared with PreTR (43.0 ± 10.8 cm/s; P < 0.05). PreTR, the reduction in PCAv observed from rest to exercise (5.2 ± 1.8%) was mitigated PostTR (P < 0.001). Similarly, exercise training enhanced ICA flow during submaximal exercise (~8.6 ± 13.7%), resulting in increased ICA flow PostTR compared with a reduced flow PreTR (P < 0.001). Although both end-tidal partial pressure of carbon dioxide and mean arterial pressure responses during incremental exercise were greater PostTR than PreTR, only the improved PETCO2 was related to the improved ICA flow (R2 = 0.14; P < 0.05). Our findings suggest that short-term exercise training improves cerebrovascular function during exercise in patients with LVADs. This finding should encourage future studies investigating long-term exercise training and cerebral and peripheral vascular adaptation.NEW & NOTEWORTHY Left ventricular assist devices, now used as destination therapy in end-stage heart failure, enable patients to undertake rehabilitative exercise training. We show, for the first time in humans, that training improves cerebrovascular function during exercise in patients with left ventricular assist devices. This finding may have implications for cerebrovascular health in patients with heart failure.

Systems toxicology assessment of a representative e-liquid formulation using human primary bronchial epithelial cells.

The development of reduced-risk products aims to provide alternatives to cigarettes that present less risk of harm for adult smokers. Responsible use of flavoring substances in these products may fulfill an important role in product acceptance. While most flavoring substances used in such products are also used by the food industry and are considered safe when ingested, their impact when inhaled may require further assessment. To aid in such an assessment, a three-step approach combining real-time cellular analysis, phenotypic high-content screening assays, and gene expression analysis was developed and tested in normal human bronchial epithelial cells with 28 flavoring substances commonly used in e-liquid formulations, dissolved individually or as a mixture in a base solution composed of propylene glycol, vegetable glycerin, and 0.6% nicotine. By employing this approach, we identified individual flavoring substances that potentially contribute greatly to the overall mixture effect (citronellol and alpha-pinene). By assessing modified mixtures, we showed that, although cytotoxic effects were found when assessed individually, alpha-pinene did not contribute to the overall mixture cytotoxicity. Most of the cytotoxic effect appeared to be attributable to citronellol, with the remaining substances contributing due to synergistic effects. We developed and used different scoring methods (Tox-Score, Phenotypic Score, and Biological Impact Factor/Network Perturbation Amplitude), ultimately enabling a ranking based on cytotoxicity, phenotypic outcome, and molecular network perturbations. This case study highlights the benefits of testing both individual flavoring substances and mixtures for e-liquid flavor assessment and emphasized the importance of data sharing for the benefit of consumer safety.

GladiaTOX: GLobal Assessment of Dose-IndicAtor in TOXicology.

SUMMARY: GladiaTOX R package is an open-source, flexible solution to high-content screening data processing and reporting in biomedical research. GladiaTOX takes advantage of the 'tcpl' core functionalities and provides a number of extensions: it provides a web-service solution to fetch raw data; it computes severity scores and exports ToxPi formatted files; furthermore it contains a suite of functionalities to generate PDF reports for quality control and data processing. AVAILABILITY AND IMPLEMENTATION: GladiaTOX R package (bioconductor). Also available via: git clone https://github.com/philipmorrisintl/GladiaTOX.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cerebral Blood Flow during Exercise in Heart Failure: Effect of Ventricular Assist Devices.

INTRODUCTION: In healthy individuals, cerebral blood flow (CBF) increases during exercise, but few studies have compared changes in CBF during exercise in patients with heart failure (HF) to healthy controls (CTRL) or assessed the effects of left ventricular assist devices (LVAD). We hypothesized that subjects implanted with LVAD would exhibit impaired cerebrovascular responses to cycle exercise when compared with age- and sex-matched healthy CTRL subjects but would have enhanced responses relative to subjects with HF. METHODS: Internal carotid artery (ICA) blood flow and intracranial middle (MCAv) and posterior cerebral (PCAv) artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental submaximal cycle ergometer exercise protocol in nine LVAD participants (58 ± 15 yr, 87 ± 16 kg, 172 ± 8 cm, six females), nine age- and sex-matched subjects with HF (58 ± 8 yr, 84 ± 11 kg, 177 ± 6 cm), and nine CTRL (55 ± 14 yr, 74 ± 16 kg, 168 ± 10 cm). RESULTS: At rest, ICA hemodynamics (velocity, shear rate, and flow) were greater in CTRL and LVAD than that in HF (P < 0.05). Higher MCAv (+5.52 ± 1.59 cm·s, P = 0.003) and PCAv (+5.82 ± 1.41 cm·s, P = 0.001) were also observed in LVAD subjects than healthy CTRL. During exercise, ICA flow increased at all workloads in CTRL, but not in HF or LVAD groups. MCAv increased from baseline in both HF and CTRL participants (P = 0.0001), but not in LVAD subjects. Nonetheless, CTRL and LVAD showed higher MCAv (P = 0.006) and PCAv (P < 0.0001) values throughout exercise than HF. CONCLUSION: Our findings indicate that LVAD subjects exhibit higher CBF at rest and during exercise than matched HF participants but attenuated brain blood flows during exercise when compared with healthy subjects. CBF should be considered when designing exercise training interventions in patients with HF and LVAD.

[HIV in Spain 2017: policies for a new management of chronicity beyond virological control]. / VIH en España 2017: políticas para una nueva gestión de la cronicidad más allá del control virológico.

The analysis of the available databases related to HIV/AIDS confirms a paradigm shift in the patient's life expectancy: now HIV has become a chronic disease, so patients are aging. However, this advance is accompanied by a negative counterpart: due to the increase in the number of years of life gained, there is a prevalence of comorbidities greater than the general population and at an earlier age. Reducing the risk associated with all the comorbidities that the ageing patient with HIV/AIDS may develop, must now be a health objective; it must be added to the traditional objectives that until now were part of the strategy to reduce the impact of the HIV infection. In the specific case of women, it is also necessary to train peri and postmenopausal women to increase their skills and motivation to care for their health; It is also very important to examine the role that hormone replacement therapy can play in reducing their symptoms.

El análisis de las bases de datos disponibles relacionadas con VIH/SIDA confirma un cambio de paradigma en la esperanza de vida del paciente: ahora el VIH se ha convertido en una enfermedad crónica, con la que los pacientes están envejeciendo. No obstante, este avance se acompaña de una contraparte negativa: debido al incremento en el número de años de vida ganados, se da una prevalencia de comorbilidades mayor a la de la población general y a una edad más temprana. Reducir el riesgo asociado a todas las comorbilidades que puede desarrollar el paciente con VIH/SIDA mientras envejece debe ser hoy en día un objetivo de salud, que se suma a los objetivos tradicionales que hasta ahora formaban parte de la estrategia para reducir el impacto de la infección por el VIH. En el caso específico de la mujer, además es necesario formar a las mujeres peri y postmenopáusicas para incrementar sus habilidades y su motivación para el cuidado de su salud; también es muy importante que se examine el rol que puede tener la terapia de reemplazo hormonal en la reducción de sus síntomas.

In vitro systems toxicology-based assessment of the potential modified risk tobacco product CHTP 1.2 for vascular inflammation- and cytotoxicity-associated mechanisms promoting adhesion of monocytic cells to human coronary arterial endothelial cells.

Cigarette smoking causes cardiovascular diseases. Heating tobacco instead of burning it reduces the amount of toxic compounds in the aerosol and may exert a reduced impact on health compared with cigarette smoke. Aqueous extract from the aerosol of a potential modified risk tobacco product, the Carbon Heated Tobacco Product (CHTP) 1.2, was compared in vitro with aqueous extract from the smoke of a 3R4F reference cigarette for its impact on the adhesion of monocytic cells to artery endothelial cells. Human coronary artery endothelial cells (HCAEC) were treated for 4 h with conditioned media from human monocytic Mono Mac 6 (MM6) cells exposed to CHTP1.2 or 3R4F extracts for 2 h or directly with those extracts freshly generated. In vitro monocyte-endothelial cell adhesion was measured concomitantly with inflammatory, oxidative stress, cytotoxicity, and death markers. Furthermore, transcriptomics analyses enabled to quantify the level of perturbation in HCAECs, and provide biological interpretation for the underlying molecular changes following exposure to 3R4F or CHTP1.2 extract. Our systems toxicology study demonstrated that approximately 10-15-fold higher concentrations of the CHTP 1.2 aerosol extract were needed to elicit similar effects as the 3R4F smoke extract on cardiovascular disease-relevant inflammation and cytotoxicity-related mechanisms and markers investigated in vitro.

VIH en España 2017: políticas para una nueva gestión de la cronicidad más allá del control virológico / HIV in Spain 2017: policies for a new management of chronicity beyond virological control

El análisis de las bases de datos disponibles relacionadas con VIH/SIDA confirma un cambio de paradigma en la esperanza de vida del paciente: ahora el VIH se ha convertido en una enfermedad crónica, con la que los pacientes están envejeciendo. No obstante, este avance se acompaña de una contraparte negativa: debido al incremento en el número de años de vida ganados, se da una prevalencia de comorbilidades mayor a la de la población general y a una edad más temprana. Reducir el riesgo asociado a todas las comorbilidades que puede desarrollar el paciente con VIH/SIDA mientras envejece debe ser hoy en día un objetivo de salud, que se suma a los objetivos tradicionales que hasta ahora formaban parte de la estrategia para reducir el impacto de la infección por el VIH. En el caso específico de la mujer, además es necesario formar a las mujeres peri y postmenopáusicas para incrementar sus habilidades y su motivación para el cuidado de su salud; también es muy importante que se examine el rol que puede tener la terapia de reemplazo hormonal en la reducción de sus síntomas

The analysis of the available databases related to HIV/AIDS confirms a paradigm shift in the patient's life expectancy: now HIV has become a chronic disease, so patients are aging. However, this advance is accompanied by a negative counterpart: due to the increase in the number of years of life gained, there is a prevalence of comorbidities greater than the general population and at an earlier age. Reducing the risk associated with all the comorbidities that the ageing patient with HIV/AIDS may develop, must now be a health objective; it must be added to the traditional objectives that until now were part of the strategy to reduce the impact of the HIV infection. In the specific case of women, it is also necessary to train peri and postmenopausal women to increase their skills and motivation to care for their health; It is also very important to examine the role that hormone replacement therapy can play in reducing their symptoms

Validación y cumplimentación de los indicadores de calidad GESIDA en pacientes con infección por el VIH / Validation and adhesion to GESIDA quality indicators in patients with HIV infection

INTRODUCCIÓN: El objetivo del estudio es validar los indicadores de calidad relevantes para la infección VIH de GESIDA, evaluando la fiabilidad, la factibilidad y la adhesión a los mismos. MÉTODOS: La fiabilidad fue evaluada mediante la reproducibilidad de 6 indicadores en revisión por pares, siendo el segundo observador una persona externa. La factibilidad y la medida del grado de cumplimiento de 22 indicadores se realizaron de forma fragmentada anual con recogida retrospectiva de la información a partir de bases de datos o de la historia clínica de los 9 hospitales participantes. RESULTADOS: La fiabilidad fue elevada con niveles de concordancia interobservador superiores al 95% en 5 de los 6 indicadores. La mediana de tiempo para realizar cada uno de los indicadores osciló entre 5 y 600 min, pero pudieron ser obtenidos progresivamente de bases de datos específicas, lo que posibilita la obtención automatizada de los mismos. En cuanto al cumplimiento de los indicadores, alcanzaron los estándares establecidos los relacionados con la evaluación inicial de los pacientes, indicación y adecuación del TAR a las guías, adherencia al TAR y seguimiento en consultas o alcanzar CV indetectables en la semana 48 del TAR. Respecto a los indicadores de prevención de infecciones oportunistas y control de comorbilidades, no se alcanzaron los estándares establecidos y se observó una heterogeneidad importante entre hospitales. CONCLUSIÓN: Los indicadores de calidad de infección VIH de GESIDA permiten medir de forma fiable y factible unos indicadores relevantes que deberían recoger todas las unidades que asisten a pacientes con infección por VIH

INTRODUCTION: The objective of the study is to validate the relevant GESIDA quality indicators for HIV infection, assessing the reliability, feasibility and adherence to them. METHODS: The reliability was evaluated using the reproducibility of 6 indicators in peer review, with the second observer being an outsider. The feasibility and measurement of the level of adherence to the 22 indicators was conducted with annual fragmented retrospective collection of information from specific databases or the clinical charts of the nine participating hospitals. RESULTS: Reliability was very high, with interobserver agreement levels higher than 95% in 5 of the 6 indicators. The median time to achieve the indicators ranged between 5 and 600 minutes, but could be achieved progressively from specific databases, enabling obtaining them automatically. As regards adherence to the indicators related with the initial evaluation of the patients, instructions and suitability of the guidelines for ART, adherence to ART, follow-up in clinics, and achieve an undetectable HIV by PCR at week 48 of the ART. Indicators of quality related to the prevention of opportunistic infections and control of comorbidities, the standards set were not achieved, and significant heterogeneity was observed between hospitals. CONCLUSION: The GESIDA quality indicators of HIV infection enabled the relevant indicators to be feasibly and reliably measured, and should be collected in all the units that care for patients with HIV infection

High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents (HPHC).

Cigarette smoke (CS) is a major risk factor for cardiovascular and lung diseases. Because CS is a complex aerosol containing more than 7,000 chemicals it is challenging to assess the contributions of individual constituents to its overall toxicity. Toxicological profiles of individual constituents as well as mixtures can be however established in vitro, by applying high through-put screening tools, which enable the profiling of Harmful and Potentially Harmful Constituents (HPHCs) of tobacco smoke, as defined by the U.S. Food and Drug Administration (FDA). For an initial assessment, an impedance-based instrument was used for a real-time, label-free assessment of the compound's toxicity. The instrument readout relies on cell adhesion, viability and morphology that all together provide an overview of the cell status. A dimensionless parameter, named cell index, is used for quantification. A set of different staining protocols was developed for a fluorescence imaging-based investigation and a HCS platform was used to gain more in-depth information on the kind of cytotoxicity elicited by each HPHC. Of the 15 constituents tested, only five were selected for HCS-based analysis as they registered a computable LD50 (< 20 mM). These included 1-aminonaphtalene, Arsenic (V), Chromium (VI), Crotonaldehyde and Phenol. Based on their effect in the HCS, 1-aminonaphtalene and Phenol could be identified to induce mitochondrial dysfunction, and, together with Chromium (VI) as genotoxic based on the increased histone H2AX phosphorylation. Crotonaldehyde was identified as an oxidative stress inducer and Arsenic as a stress kinase pathway activator. This study demonstrates that a combination of impedance-based and HCS technologies provides a robust tool for in vitro assessment of CS constituents.

A framework for in vitro systems toxicology assessment of e-liquids.

Various electronic nicotine delivery systems (ENDS), of which electronic cigarettes (e-cigs) are the most recognized prototype, have been quickly gaining ground on conventional cigarettes because they are perceived as less harmful. Research assessing the potential effects of ENDS exposure in humans is currently limited and inconclusive. New products are emerging with numerous variations in designs and performance parameters within and across brands. Acknowledging these challenges, we present here a proposed framework for an in vitro systems toxicology assessment of e-liquids and their aerosols, intended to complement the battery of assays for standard toxicity assessments. The proposed framework utilizes high-throughput toxicity assessments of e-liquids and their aerosols, in which the device-to-device variability is minimized, and a systems-level investigation of the cellular mechanisms of toxicity is an integral part. An analytical chemistry investigation is also included as a part of the framework to provide accurate and reliable chemistry data solidifying the toxicological assessment. In its simplest form, the framework comprises of three main layers: (1) high-throughput toxicity screening of e-liquids using primary human cell culture systems; (2) toxicity-related mechanistic assessment of selected e-liquids, and (3) toxicity-related mechanistic assessment of their aerosols using organotypic air-liquid interface airway culture systems. A systems toxicology assessment approach is leveraged to enable in-depth analyses of the toxicity-related cellular mechanisms of e-liquids and their aerosols. We present example use cases to demonstrate the suitability of the framework for a robust in vitro assessment of e-liquids and their aerosols.

[Validation and adhesion to GESIDA quality indicators in patients with HIV infection]. / Validación y cumplimentación de los indicadores de calidad GESIDA en pacientes con infección por el VIH.

INTRODUCTION: The objective of the study is to validate the relevant GESIDA quality indicators for HIV infection, assessing the reliability, feasibility and adherence to them. METHODS: The reliability was evaluated using the reproducibility of 6 indicators in peer review, with the second observer being an outsider. The feasibility and measurement of the level of adherence to the 22 indicators was conducted with annual fragmented retrospective collection of information from specific databases or the clinical charts of the nine participating hospitals. RESULTS: Reliability was very high, with interobserver agreement levels higher than 95% in 5 of the 6 indicators. The median time to achieve the indicators ranged between 5 and 600minutes, but could be achieved progressively from specific databases, enabling obtaining them automatically. As regards adherence to the indicators related with the initial evaluation of the patients, instructions and suitability of the guidelines for ART, adherence to ART, follow-up in clinics, and achieve an undetectable HIV by PCR at week 48 of the ART. Indicators of quality related to the prevention of opportunistic infections and control of comorbidities, the standards set were not achieved, and significant heterogeneity was observed between hospitals. CONCLUSION: The GESIDA quality indicators of HIV infection enabled the relevant indicators to be feasibly and reliably measured, and should be collected in all the units that care for patients with HIV infection.