An illness-death multistate model to implement delta adjustment and reference-based imputation with time-to-event endpoints.

With a treatment policy strategy, therapies are evaluated regardless of the disturbance caused by intercurrent events (ICEs). Implementing this estimand is challenging if subjects are not followed up after the ICE. This circumstance can be dealt with using delta adjustment (DA) or reference-based (RB) imputation. In the survival field, DA and RB imputation have been researched so far using multiple imputation (MI). Here, we present a fully analytical solution. We use the illness-death multistate model with the following transitions: (a) from the initial state to the event of interest, (b) from the initial state to the ICE, and (c) from the ICE to the event. We estimate the intensity function of transitions (a) and (b) using flexible parametric survival models. Transition (c) is assumed unobserved but identifiable using DA or RB imputation assumptions. Various rules have been considered: no ICE effect, DA under proportional hazards (PH) or additive hazards (AH), jump to reference (J2R), and (either PH or AH) copy increment from reference. We obtain the marginal survival curve of interest by calculating, via numerical integration, the probability of transitioning from the initial state to the event of interest regardless of having passed or not by the ICE state. We use the delta method to obtain standard errors (SEs). Finally, we quantify the performance of the proposed estimator through simulations and compare it against MI. Our analytical solution is more efficient than MI and avoids SE misestimation-a known phenomenon associated with Rubin's variance equation.

ALK-Fusion Transcripts Can Be Detected in Extracellular Vesicles (EVs) from Nonsmall Cell Lung Cancer Cell Lines and Patient Plasma: Toward EV-Based Noninvasive Testing.

BACKGROUND: ALK rearrangements are present in 5% of nonsmall cell lung cancer (NSCLC) tumors and identify patients who can benefit from ALK inhibitors. ALK fusions testing using liquid biopsies, although challenging, can expand the therapeutic options for ALK-positive NSCLC patients considerably. RNA inside extracellular vesicles (EVs) is protected from RNases and other environmental factors, constituting a promising source for noninvasive fusion transcript detection. METHODS: EVs from H3122 and H2228 cell lines, harboring EML4-ALK variant 1 (E13; A20) and variant 3 (E6a/b; A20), respectively, were successfully isolated by sequential centrifugation of cell culture supernatants. EVs were also isolated from plasma samples of 16 ALK-positive NSCLC patients collected before treatment initiation. RESULTS: Purified EVs from cell cultures were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. Western blot and confocal microscopy confirmed the expression of EV-specific markers as well as the expression of EML4-ALK-fusion proteins in EV fractions from H3122 and H2228 cell lines. In addition, RNA from EV fractions derived from cell culture was analyzed by digital PCR (dPCR) and ALK-fusion transcripts were clearly detected. Similarly, plasma-derived EVs were characterized by NTA, flow cytometry, and the ExoView platform, the last showing that EV-specific markers captured EV populations containing ALK-fusion protein. Finally, ALK fusions were identified in 50% (8/16) of plasma EV-enriched fractions by dPCR, confirming the presence of fusion transcripts in EV fractions. CONCLUSIONS: ALK-fusion transcripts can be detected in EV-enriched fractions. These results set the stage for the development of EV-based noninvasive ALK testing.

Phosphoproteomic Analysis of Platelets in Severe Obesity Uncovers Platelet Reactivity and Signaling Pathways Alterations.

OBJECTIVE: Obesity is associated with a proinflammatory and prothrombotic state that supports atherosclerosis progression. The goal of this study was to gain insights into the phosphorylation events related to platelet reactivity in obesity and identify platelet biomarkers and altered activation pathways in this clinical condition. Approach and Results: We performed a comparative phosphoproteomic analysis of resting platelets from obese patients and their age- and gender-matched lean controls. The phosphoproteomic data were validated by mechanistic, functional, and biochemical assays. We identified 220 differentially regulated phosphopeptides, from at least 175 proteins; interestingly, all were up-regulated in obesity. Most of the altered phosphoproteins are involved in SFKs (Src-family kinases)-related signaling pathways, cytoskeleton reorganization, and vesicle transport, some of them validated by targeted mass spectrometry. To confirm platelet dysfunction, flow cytometry assays were performed in whole blood indicating higher surface levels of GP (glycoprotein) VI and CLEC (C-type lectin-like receptor) 2 in platelets from obese patients correlating positively with body mass index. Receiver operator characteristics curves analysis suggested a much higher sensitivity for GPVI to discriminate between obese and lean individuals. Indeed, we also found that obese platelets displayed more adhesion to collagen-coated plates. In line with the above data, soluble GPVI levels-indicative of higher GPVI signaling activation-were almost double in plasma from obese patients. CONCLUSIONS: Our results provide novel information on platelet phosphorylation changes related to obesity, revealing the impact of this chronic pathology on platelet reactivity and pointing towards the main signaling pathways dysregulated.

Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention.

Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague-Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity.

Platelet Lipidome Fingerprint: New Assistance to Characterize Platelet Dysfunction in Obesity.

Obesity is associated with a pro-inflammatory and pro-thrombotic state that supports atherosclerosis progression and platelet hyper-reactivity. During the last decade, the platelet lipidome has been considered a treasure trove, as it is a source of biomarkers for preventing and treating different pathologies. The goal of the present study was to determine the lipid profile of platelets from non-diabetic, severely obese patients compared with their age- and sex-matched lean controls. Lipids from washed platelets were isolated and major phospholipids, sphingolipids and neutral lipids were analyzed either by gas chromatography or by liquid chromatography coupled to mass spectrometry. Despite a significant increase in obese patient's plasma triglycerides, there were no significant differences in the levels of triglycerides in platelets among the two groups. In contrast, total platelet cholesterol was significantly decreased in the obese group. The profiling of phospholipids showed that phosphatidylcholine and phosphatidylethanolamine contents were significantly reduced in platelets from obese patients. On the other hand, no significant differences were found in the sphingomyelin and ceramide levels, although there was also a tendency for reduced levels in the obese group. The outline of the glycerophospholipid and sphingolipid molecular species (fatty-acyl profiles) was similar in the two groups. In summary, these lipidomics data indicate that platelets from obese patients have a unique lipid fingerprint that may guide further studies and provide mechanistic-driven perspectives related to the hyperactivate state of platelets in obesity.

Development of Radiosterilized Porcine Skin Electrosprayed with Silver Nanoparticles Prevents Infections in Deep Burns.

Extensive burns represent a significant challenge in biomedicine due to the multiple systemic and localized complications resulting from the major skin barrier loss. The functionalization of xenografts with nanostructured antibacterial agents proposes a fast and accessible application to restore barrier function and prevent localized bacterial contamination. Based on this, the objective of this work was to functionalize a xenograft by electrospray deposition with silver nanoparticles (AgNPs) and to evaluate its antibiofilm and cytotoxic effects on human fibroblasts. Initially, AgNPs were synthesized by a green microwave route with sizes of 2.1, 6.8, and 12.2 nm and concentrations of 0.055, 0.167, and 0.500 M, respectively. The AgNPs showed a size relationship directly proportional to the concentration of AgNO3, with a spherical and homogeneous distribution determined by high-resolution transmission electron microscopy. The surface functionalization of radiosterilized porcine skin (RPS) via electrospray deposition with the three AgNP concentrations (0.055, 0.167, and 0.500 M) in the epidermis and the dermis showed a uniform distribution on both surfaces by energy-dispersive X-ray spectroscopy. The antibiofilm assays of clinical multidrug-resistant Pseudomonas aeruginosa showed significant effects at the concentrations of 0.167 and 0.500 M, with a log reduction of 1.3 and 2.6, respectively. Additionally, viability experiments with human dermal fibroblasts (HDF) exposed to AgNPs released from functionalized porcine skin showed favorable tolerance, with retention of viability more significant than 90% for concentrations of 0.05 and 0.167 M after 24 h exposure. Antibacterial activity combined with excellent biocompatibility makes this biomaterial a candidate for antibacterial protection by inhibiting bacterial biofilms in deep burns during early stages of development.

Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy.

BACKGROUND & AIMS: There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. METHODS: Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. RESULTS: Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis (n = 28, 70%). Previous treatments included an NS3-inhibitor (30%), an NS5A-inhibitor (100%) and SOF (85%). Baseline RAS data from a subgroup of patients before VOX/VEL/SOF retreatment (78%) showed few NS3 RASs apart from Q80K in GT1a (40%), typical NS5A RAS patterns in most patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure was available in 98% of patients and showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n = 2) or with SOF±ribavirin (n = 15), VOX/VEL/SOF±ribavirin (n = 4) or VEL/SOF and ribavirin (n = 1) for 12 to 24 weeks. Sustained virologic response was achieved in 17/21 (81%) patients with a final treatment outcome. Of these, 2 GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF or glecaprevir/pibrentasvir+SOF+ribavirin, and 2 patients with cirrhosis died during treatment or before reaching SVR12. CONCLUSIONS: VOX/VEL/SOF failure was mainly observed in HCV GT3- and GT1a-infected patients with cirrhosis and was not associated with specific RAS patterns within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in most patients. LAY SUMMARY: The advent of direct-acting antivirals has enabled the effective cure of chronic hepatitis C in most patients. However, treatment failure occurs in some patients, who are often retreated with a combination regimen called VOX/VEL/SOF, which is associated with very high rates of cure. However, VOX/VEL/SOF retreatment also fails in some patients. Herein, we analysed samples from patients in whom VOX/VEL/SOF retreatment failed and we assessed the efficacy of different rescue therapies, showing that rescue treatment is effective in most patients (81%).

Safety of Large-Volume Immediate Fat Grafting for Latissimus Dorsi-Only Breast Reconstruction: Results and Related Complications in 95 Consecutive Cases.

BACKGROUND: Breast reconstruction with implants has proven serious complications, mostly in patients who have undergone radiotherapy. In these cases, autologous reconstruction is the technique of choice. OBJECTIVES: To study if breast reconstruction using latissimus dorsi and immediate fat grafting (LIFG) is a widely applicable technique for those cases in which an autologous reconstruction is desirable, but the use of microsurgical perforator flaps is not available. METHODS: Data of 95 consecutive breast reconstructions from May 2014 to December 2018 were prospectively collected. All patients included in the study had a minimum follow-up of one year after completion of the reconstructive process. RESULTS: The mean age of the patients was 48.57 years with an average follow-up of 20.65 months. The mean number of surgeries per patient was 1.61. In 47.4% of the cases, only LIFG surgery was required to accomplish the reconstructive process. The mean volume of fat graft used was 416.00 ± 145.79 cc. Relevant statistically significant differences in the volume of graft were found regarding the use of previous radiotherapy and the timing of reconstruction. Radiological fat necrosis nodes were the main complication (15.8%). However, their presence was significantly lower if no additional fat grafting sessions were necessary, though, unexpectedly, no relation was found in relation to the total amount of fat graft needed. CONCLUSIONS: LIFG has proved to be a safe and reliable method for total autologous breast reconstruction. Even when a medium to large size is required, a large volume of fat graft is accepted; thus, excellent results can be obtained. It is an interesting alternative for breast reconstruction, in addition to abdominal perforator flaps. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . Breast Surgery.

Effect of Power Ultrasound Treatment on Free and Glycosidically-Bound Volatile Compounds and the Sensorial Profile of Red Wines.

This study presents the effect of the application of high-power ultrasound to crushed grapes, at a winery-scale, on the content of varietal volatile compounds (free and glycosidically-bound) in musts and on the overall aroma of wines. Two different frequencies (20 kHz and 28 kHz) were tested and the combination of grape sonication and different maceration times on wine aroma was also evaluated. The volatile compounds were isolated by solid phase extraction and analyzed by gas chromatography-mass spectrometry, carrying out a sensory evaluation of wines by quantitative descriptive analysis. Sonication produced an increase in the concentration of free varietal compounds such as C6 alcohols, terpenes and norisoprenoids in musts and also in wines made by 48 h of skin maceration, being less efficient in the extraction of the bound fraction. Fermentation compounds were also positively affected by ultrasound treatment, although this effect was variable depending on the frequency used, the maceration time and the type of compound. All the wines made from sonicated grapes had better scores in the evaluated olfactory attributes with respect to the control wines. Our results indicate that sonication could produce an increase in the content of some volatile compounds of sensory relevance, obtaining wines with an aroma quality similar or higher than those elaborated with longer maceration times.

A Feasibility Trial of an Online-Only, Family-Centered Preventive Intervention for Hispanics: e-Familias Unidas.

We piloted the preventive intervention e-Familias Unidas, delivered exclusively through the Internet to maximize reach and sustainability. This program is an adaptation of an evidence-based, family-centered intervention that aims to prevent Hispanic adolescent drug use and risky sexual behavior through improving family functioning. The purpose of this feasibility trial was to: (1) explore the use of Facebook and a trusted community champion in the online recruitment of Hispanic parents of adolescents, (2) test an online-only assessment and randomization protocol, (3) pilot intervention delivery via e-familiasunidas.com, and (4) assess pre-post changes in family functioning. We tracked participant recruitment and enrollment via Facebook analytics and REDCap. Intervention completion was tracked via our website. We conducted an ANCOVA to test for between group (e-Familias Unidas vs. control) differences post-intervention. Recruitment lasted for a total of 10 weeks and was divided into three phases, with each phase systematically assessing which strategies maximized recruitment and enrollment. Overall, 93 Hispanic parents enrolled in the study. Of those randomized to the intervention group (n = 46), 70% were engaged and watched an average of 5.4 out of the 12 online videos. We found that participants recruited through a community champion, versus Facebook advertisements, had higher rates of enrollment and intervention completion. There was a significant improvement in parent-adolescent communication for parents who received e-Familias Unidas compared to those in the control group (n = 47). This pilot trial demonstrated it is feasible to recruit, assess, and deliver e-Familias Unidas to Hispanic parents through an online-only platform. Our findings highlight the promise of an online platform to optimize the reach of preventive interventions for underserved populations, to more effectively target participants, and to disseminate sustainable evidence-based interventions. We discuss lessons learned and recommendations for future research.

Pretreatment of tamarind pericarp to increase antioxidant availability and its application in a functional food.

Diverse researchers have considered by-products of food and agricultural processing industries as a source of antioxidants. Tamarind (Tamarindus indica) is a leguminous tree, native from tropical Africa bearing edible fruit. The fruit is composed of 30% pulp, 40% seed, and 30% pericarp. Currently, tamarind pericarp is a waste from tamarind processing (approximately 54,400 tons of pericarp in 2012 worldwide) and is contributing to environmental contamination. This research aimed to determine the effect of maceration, microwaves, and ultrasound on the increase in the antioxidant availability in tamarind pericarp and its incorporation as a functional ingredient in cookies (5 and 10% substitution). Antioxidant content, antioxidant activity, proximate, and sensorial analysis of the cookies were conducted. The microwave method was the best pretreatment compared with sonication and maceration since it showed 1.3-fold higher amounts of phenolic compounds and 1.2-fold higher antioxidant capacity. The 10% substitution of tamarind pericarp powder in cookies, significantly increased the fiber content (four-fold) and phenolic compounds content (2.6-fold) and the product presented good acceptance in a sensorial test. Thus, tamarind pericarp powder could be considered as an antioxidant and fiber source and could be used as a functional ingredient in food products.

MMRM vs joint modeling of longitudinal responses and time to study drug discontinuation in clinical trials using a "de jure" estimand.

In pre-marketing stages of drug development, trialists focus on drug efficacy rather than effectiveness, and observations collected after study drug discontinuation are excluded from the analysis, following the so-called "de jure" estimand. In this setting, mixed models for repeated measures (MMRM) are becoming the benchmark to analyze normally distributed longitudinal responses. We have compared the performance of MMRM against shared parameter models (SPM) that jointly fit the longitudinal response and time to study drug discontinuation. Our simulations have first confirmed that MMRM lead to biased treatment effect estimates when longitudinal and event processes are associated via latent shared parameters, especially if the relationship is heterogeneous across treatment groups. SPM produced unbiased estimates with SPM data but faced two important obstacles: (a) SPM led to considerable bias when treatment discontinuation and response were associated with models of the time-varying covariates (TVC) family, and (b) SPM were rather sensitive to the choice of the parameterization to model the relationship between longitudinal and time-to-event processes. When we simulated SPM data but used an incorrect equation to relate the random effects and time-to-event response, SPM led to a bigger bias than that seen with MMRM. We have finally evaluated a methodology to choose between MMRM and SPM consisting of expanding the MMRM density into the likelihood of both longitudinal and time-to-event data by plugging in the likelihood of a parametric TVC model. This approach allowed us to accurately select the optimal tool (MMRM or SPM) with sample sizes typical of phases 2b and 3.

Deciphering Adipose Tissue Extracellular Vesicles Protein Cargo and Its Role in Obesity.

The extracellular vesicles (EVs) have emerged as key players in metabolic disorders rising as an alternative way of paracrine/endocrine communication. In particular, in relation to adipose tissue (AT) secreted EVs, the current knowledge about its composition and function is still very limited. Nevertheless, those vesicles have been lately suggested as key players in AT communication at local level, and also with other metabolic peripheral and central organs participating in physiological homoeostasis, and also contributing to the metabolic deregulation related to obesity, diabetes, and associated comorbidities. The aim of this review is to summarize the most relevant data around the EVs secreted by adipose tissue, and especially in the context of obesity, focusing in its protein cargo. The description of the most frequent proteins identified in EVs shed by AT and its components, including their changes under pathological status, will give the reader a whole picture about the membrane/antigens, and intracellular proteins known so far, in an attempt to elucidate functional roles, and also suggesting biomarkers and new paths of therapeutic action.

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes.

Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.

Essential and xenobiotic elements in cottage cheese from the Slovak market with a consumer risk assessment.

The examination of various elements in the milk products is very important in the food sector in respect of food quality and safety. The aim of this study was to determine the concentrations of calcium (Ca), cobalt (Co), cadmium (Cd), copper (Cu), chromium (Cr), iron (Fe), mercury (Hg), potassium (K), magnesium (Mg), sodium (Na), nickel (Ni), phosphorus (P), lead (Pb) and zinc (Zn) in white cottage cheese or cottage cheese supplemented with various additives (white, lacto-free, chive, tzatziki, mustard + onion, chili, active protein) available on the market of Slovakia. All essential elements were within the reference range. Cottage cheese enriched with tzatziki showed higher amount of Cu, Fe, K, and Zn. Mustard + onion cheese contained high values of Ca, Co, Mg, and Ni. In white cottage cheese high amount of Cr, Mn, and P was measured. The content of xenobiotic metals was below permitted limit. The contribution to PTWI (Provisional tolerable weekly intake) suggested very low dietary exposure to heavy metals as Cd, Hg, and Pb as well as other metals (Cu, Ni, and Zn) in cottage cheese. Numerous correlations between concentrations were observed. MOE (Margin of Exposure) evaluation denoted that average consumption of cottage cheese does not pose any high cardiovascular and nephrotoxicity threat.

A Combination of Proteomic Approaches Identifies A Panel of Circulating Extracellular Vesicle Proteins Related to the Risk of Suffering Cardiovascular Disease in Obese Patients.

Plasma-derived extracellular vesicles (EVs) have been extensively described as putative biomarkers in different diseases. Interestingly, increased levels of EVs subpopulations are well known to associate with obesity. The goal of this study is to identify EVs-derived biomarkers in plasma from obese patients in order to predict the development of pathological events associated with obesity. Samples are obtained from 22 obese patients and their lean-matched controls are divided into two cohorts: one for a 2D fluorescence difference gel electrophoresis (2D-DIGE)-based study, and the other one for a label free LC-MS/MS-based approach. EVs are isolated following a serial ultracentrifugation protocol. Twenty-two and 23 differentially regulated features are detected from 2D-DIGE and label free LC-MS/MS, respectively; most of them involve in the coagulation and complement cascades. Remarkably, there is an upregulation of complement C4, complement C3, and fibrinogen in obese patients following both approaches, the latter two also validated by 2D-western-blotting in an independent cohort. These results correlate with a proinflammatory and prothrombotic state of those individuals. On the other hand, a downregulation of adiponectin leading to an increased risk of suffering cardiovascular diseases has been shown. The results suggest the relevance of plasma-derived-EVs proteins as a source of potential biomarkers for the development of atherothrombotic events in obesity.

Cortisol and IgA are Involved in the Progression of Alzheimer's Disease. A Pilot Study.

It is known that stress and immune systems are related with Alzheimer's disease (AD). However, the relationship of both systems in the progression of disease is not clearly demonstrated. Hair cortisol and salivary immunoglobulin A (IgA) were quantified in 49 patients with mild, moderate, and severe AD. A significant change was seen in both molecules as AD progressed from mild to moderate and severe. Low levels of cortisol were observed in mild AD patients compared with moderate and severe. However, IgA showed a contrary pattern. High levels were observed in mild AD patientes but low in moderate and severe AD subjects. The secretion of cortisol and IgA seems to be very different at the start compared with posterior development of AD suggesting that neuroinflammation can be involved. Both molecules could be used as possible therapeutical tools.

An ethnographic study of human dignity in nursing practice.

BACKGROUND: The ethical values of nursing are crucial to the provision of humane care. Human dignity is a core value that must be preserved in order to deliver such care. No studies to date have compared the perceptions of nurses and/or patients regarding the components of dignified care embedded in actual clinical practice. PURPOSE: To explore the delivery of dignified care by professional nurses. This was an ethnographic qualitative study combining inductive and deductive methods to identify emergent themes. A multicenter study carried out in the internal medicine units of four hospitals in Barcelona (Spain). Convenience sampling was used to recruit nurses from the four units. SETTING AND SAMPLE: Multicenter study carried out in the internal medicine units of four hospitals in Barcelona (Spain). Convenience sampling was used to recruit nurses from the four units. METHOD: We conducted 158 hours of participant observation of 27 nurses. Semi-structured individual interviews were undertaken with 20 of these nurses, with data saturation being reached. Data were collected between September 2014 and May 2016 and were analysed using ATLAS.ti 7.2 for Windows. RESULTS: Two themes emerged from the analysis: Delivering dignified care and Factors influencing the delivery of dignified care. The nurses regarded human dignity as one of the key values of their profession. However, there was a discrepancy between their perceptions of the care they offered and what they actually did, due mainly to a lack of awareness about their own practice. Respect, confidentiality, privacy and communication were identified as the key elements underpinning dignified care. Institutional policies were seen as the major obstacle to the delivery of humane care, the key issues being frequent shift rotations, a high patient-nurse ratio and excessive paperwork. CONCLUSIONS: The results of this study underline the importance of delivering dignified care and the need to ensure that nurses' attitudes and behaviours are consistent with this goal. The ethnographic approach, combining participant observation with individual interviews, revealed discrepancies between nurses' perceptions of the care they offered, or should offer, and what they actually did. This suggests a need for professional forums in which nurses can become more aware of their own clinical practice.

Overview on radiation and tissue banking in Latin America.

The International Atomic Energy Agency (IAEA) played an important role in the establishment of new tissue banks and the improvement of already existing ones in Latin America. The Agency strongly supported, through regional, interregional and national technical cooperation projects, providing equipment, expert missions and training for the production and application of human tissues for transplantation. From 1999 to 2005 five regional courses were given in Buenos Aires under the modality of 1-year distance learning training courses and 1-week face to face courses. The courses were organized by the IAEA, through the National Atomic Energy Commission (CNEA) and the Faculty of Medicine of Buenos Aires University as Post Graduate Specialization Course. In 2005 the Latin American countries joined with Spain and Portugal, and created the Ibero American Network Council of Donation and Transplant (Red Consejo Iberoamericano de Donación y Trasplantes-RCIDT). The objective of this network is to cooperate among twenty-one Ibero American countries in organizational and legislative aspects, training of professionals, and ethical and social issues related to the donation and transplantation of organs, tissues and cells. The members of this Network work actively to harmonize the regulations and the control of donation and transplantation of human organs, tissues and cells. At present, in Latin America, more than 220 facilities of tissues banks are operating and tissue allografts are being produced by single and multi-tissue banks. The efforts made by the governments and professionals from the region allow the tissue banks to operate under quality systems and introduce new technologies.

Differential effects of MDMA and cocaine on inhibitory avoidance and object recognition tests in rodents.

INTRODUCTION: Drug addiction continues being a major public problem faced by modern societies with different social, health and legal consequences for the consumers. Consumption of psychostimulants, like cocaine or MDMA (known as ecstasy) are highly prevalent and cognitive and memory impairments have been related with the abuse of these drugs. AIM: The aim of this work was to review the most important data of the literature in the last 10 years about the effects of cocaine and MDMA on inhibitory avoidance and object recognition tests in rodents. DEVELOPMENT: The object recognition and the inhibitory avoidance tests are popular procedures used to assess different types of memory. We compare the effects of cocaine and MDMA administration in these tests, taking in consideration different factors such as the period of life development of the animals (prenatal, adolescence and adult age), the presence of polydrug consumption or the role of environmental variables. Brain structures involved in the effects of cocaine and MDMA on memory are also described. CONCLUSIONS: Cocaine and MDMA induced similar impairing effects on the object recognition test during critical periods of lifetime or after abstinence of prolonged consumption in adulthood. Deficits of inhibitory avoidance memory are observed only in adult rodents exposed to MDMA. Psychostimulant abuse is a potential factor to induce memory impairments and could facilitate the development of future neurodegenerative disorders.