Impaired intratumoral dendritic cell function and potential predictive value of dendritic cell markers for metastasis in malignant salivary gland tumors.

BACKGROUND: The differentiation between primary and metastatic salivary gland neoplasms (SGNs) helps in determining appropriate management strategies, including the need for additional diagnostic tests, surveillance, or aggressive treatment. The purpose of this study was to identify and quantify the immature and mature dendritic cells (DCs) in metastatic and no metastatic SGNs and determine its association with clinicopathological findings. MATERIAL AND METHODS: Cross-sectional, observational, and descriptive study that includes 33 malignant salivary gland neoplasms [MSGN (6, 18.1% metastatic)], and 22 pleomorphic adenomas (PA), as a control group. Clinical and histopathological characteristics were obtained. Immunohistochemistry for human leukocyte antigen D-related (HLA-DR), CD1a, CD83, and Ki-67 proteins was done. Positive intra- and peritumoral DCs were counted. RESULTS: Individuals with MSGN had a lower density of intratumoral HLA-DR+ cells than those with PA (p=0.001), Ki-67 immunostaining was significantly higher in MSGN than in PA (6% vs. 1.4%, p<0.001). Metastatic MSGN showed less intratumoral CD1a+ than non-metastatic (3.2 vs. 165.1, p=0.001). No differences in intra- and peritumoral CD83+ cells were found between benign and malignant SGN. CONCLUSIONS: These results suggest that the immune-protective function of intratumoral DCs is compromised in MSGNs. DCs markers may represent useful prediction tools for metastases in salivary gland malignancies, with crucial implications in the implementation of appropriate disease management strategies.

Water associated with residential areas and tourist resorts is the key predictor of Asian tiger mosquito presence on a Mediterranean island.

The Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae), is a highly invasive species and a vector of several viruses of serious concern to public health. Investigating the habitat selection of this species at small to medium scales is essential to the planning of effective prevention and control campaigns. The present group considered detailed data for this species' presence/absence collected at 228 sites on Mallorca Island (Spain) in autumn 2015, 3 years after the first detection of the species on the island. Site occupancy models accounting for false negative detections and imperfect monitoring were used to evaluate the relationships between mosquito presence and habitat variables. In the study area, mosquito presence was negatively associated with altitude, probably as a result of greater human presence at low altitudes near the coast. Moreover, the presence of Ae. albopictus was positively associated with swimming pools as a result of associated gardens, plants and sources of fresh water. These two variables were combined to predict the presence of the species across the entire island.

Static and elevated pollen traps do not provide an accurate assessment of personal pollen exposure.

SUMMARY: Background. Volumetric pollen traps are commonly used to assess pollen exposure. These traps are well suited for estimating the regional mean airborne pollen concentration but are likely not to provide an accurate index of personal exposure. In this study, we tested the hypothesis that hair sampling may provide different pollen counts from those from pollen traps, especially when the pollen exposure is diverse. Methods. We compared pollen counts in hair washes to counts provided by stationary volumetric and gravimetric pollen traps in 2 different settings: urban with volunteers living in short distance from one another and from the static trap and suburban in which volunteers live in a scattered environment, quite far from the static trap. Results. Pollen counts in hair washes are in full agreement with trap counts for uniform pollen exposure. In contrast, for diverse pollen exposure, .individual pollen counts in hair washes vary strongly in quantity and taxa composition between individuals and dates. These results demonstrate that the pollen counts method (hair washes vs. stationary pollen traps) may lead to different absolute and relative contributions of taxa to the total pollen count. Conclusions. In a geographic area with a high diversity of environmental exposure to pollen, static pollen traps, in contrast to hair washes, do not provide a reliable estimate of this higher diversity.

Optomechanics with silicon nanowires by harnessing confined electromagnetic modes.

The optomechanical coupling that emerges in an optical cavity in which one of the mirrors is a mechanical resonator has allowed sub-Kelvin cooling with the prospect of observing quantum phenomena and self-sustained oscillators with very high spectral purity. Both applications clearly benefit from the use of the smallest possible mechanical resonator. Unfortunately, the optomechanical coupling largely decays when the size of the mechanical system is below the light wavelength. Here, we propose to exploit the optical resonances associated to the light confinement in subwavelength structures to circumvent this limitation, efficiently extending optomechanics to nanoscale objects. We demonstrate this mechanism with suspended silicon nanowires. We are able to optically cool the mechanical vibration of the nanowires from room temperature to 30-40 K or to obtain regenerative mechanical oscillation with a frequency stability of about one part per million. The reported optomechanical phenomena can be exploited for developing cost-optimized mass sensors with sensitivities in the zeptogram range.

Hormone sensitive protocol for metastatic prostate cancer, an update.

To review and update last protocols in hormone sensitive metastatic prostate cancer for improving clinical management in routine. Evidence analysis available about recent updates protocols in hormone sensitive metastatic prostate cancer according to expert panel of clinicians about this field. A nominal consensus group for unify and improve the recommendations to the management of sensitive metastatic prostate cancer patients is currently needed. This document unifies and improve the management of patients with hormone sensitive metastatic prostate cancer, with a methodology that combines data quantitative and qualitative and based on the participation of a broad scientific committee appointed by the Spanish Association of Urology.

Optimization and shelf life of a low-lactose yogurt with Lactobacillus rhamnosus HN001.

Lactose intolerance results in gastrointestinal discomfort and the malabsorption of certain nutrients, such as calcium. The replacement of milk with low-lactose and probiotic-enriched dairy products is an effective strategy of mitigating the symptoms of lactose intolerance. Lactobacillus rhamnosus HN001 (HN001) is a safe, immunity-stimulating probiotic. We have developed a process to increase the hydrolysis of lactose and HN001 growth in yogurt versus ß-galactosidase (ßG) concentration and enzymatic hydrolysis time (EHT) before bacterial fermentation. The objective of this study was to optimize the conditions by which yogurt is processed as a function of ßG and EHT using a multifactorial design, with lactose content, HN001 growth, process time, and sensory quality as dependent variables. Further, the shelf life of the optimized yogurt was evaluated. In the optimization study, polynomials explained the dependent variables. Based on Pearson correlation coefficients, HN001 growth correlated positively with the hydrolysis of lactose. However, low lactose content and high HN001 count increased the fermentation time and lowered the sensory quality. The optimized conditions-using polynomials to obtain yogurt with >1 × 10(7) cfu of HN001/mL, <10 g of lactose/L, and a minimum overall sensory quality of 7 on the Karlsruhe scale-yielded a theoretical value of 910 neutral lactose units/kg for ßG and 2.3h for EHT, which were validated in an industrial-scale assay. Based on a shelf-life study at 3 temperatures, the hydrolysis of lactose and the growth of HN001 continue during storage. Arrhenius equations were developed for the variables in the shelf-life study. Our results demonstrate that it is feasible to develop a low-lactose yogurt to which HN001 has been added for lactose-intolerant persons who wish to strengthen their immune system.

A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper.

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

Health-related quality of life of X-linked hypophosphatemia in Spain.

BACKGROUND: Health-related quality of life (HRQoL) of patients with X-linked hypophosphatemia (XLH) is lower than that of both the general population and the patients with other chronic diseases, mainly due to diagnostic delay, treatment difficulties, poor psychosocial support, and problems with social integration. Early diagnosis and optimal treatment are paramount to control the disease in patients with XLH, avoid complications, and maintain or improve their HRQoL. We, therefore, analyzed the HRQoL of pediatric and adult patients with XLH treated with conventional therapy in Spain. RESULTS: We used several versions of the EuroQol-5 dimensions (EQ-5D) instrument according to the age of patients with XLH. Then we compared the HRQoL of patients to that of the general Spanish population. Children with XLH (n = 21) had moderate problems in walking about (61.9%), washing or dressing themselves (9.52%), and performing their usual activities (33.33%). They also felt moderate pain or discomfort (61.9%) and were moderately anxious or depressed (23.81%). Adults with XLH (n = 29) had lower HRQoL, with problems in walking (93%, with 3.45% unable to walk independently), some level of pain (86%, with 3.45% experiencing extreme pain), problems with their usual activities (80%) and self-care (> 50%), and reported symptoms of anxiety and/or depression (65%). There were important differences with the general Spanish population. CONCLUSIONS: XLH impacts negatively on physical functioning and HRQoL of patients. In Spanish patients with XLH, the HRQoL was reduced despite conventional treatment, clearly indicating the need to improve the therapeutic approach to this disorder.

X-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affectingX-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affecting bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.

Impairment of rapid repetitive finger movements and visual reaction time in patients with essential tremor.

BACKGROUND AND PURPOSE: The question whether patients with essential tremor (ET) have slowed movements as part of their clinical manifestations is still a matter of controversy. We analyzed basic motor function in patients with ET and in healthy matched controls. METHODS: We studied 61 patients with ET and 122 age- and sex-matched controls. Evaluation included four timed tests (pronation-supination, finger tapping and movement between two points, all with both hands, and walking test); and three tests performed on a personal computer (speed for pressing repetitively a key - frequency, visual reaction time and movement time, all with both hands). RESULTS: Essential tremor patients showed higher mean values for right and left finger tapping, left movement between two points; and with right and left frequency and reaction time. In the logistic regression study, ET patients showed significantly higher values than controls for right and left finger tapping; mean, SD, maximum and rank values of right and left frequency; and mean, SD, minimum, maximum and rank values of right and left visual reaction time. Tremor severity was not correlated with the altered values. CONCLUSIONS: Patients with ET showed impaired motor performance, at least in some tasks, such as rapid repetitive finger movements (finger tapping and frequency) and visual reaction time (impairment was not related with tremor severity). This probably means that patients with ET have some degree of bradykinesia.

Nutritional Risk and Mortality at One Year for Elderly Patients Hospitalized with Nonvalvular Atrial Fibrillation. Nonavasc Registry.

OBJECTIVES: To determine whether nutritional risk is associated with the mortality of elderly patients hospitalized with nonvalvular atrial fibrillation (NVAF). DESIGN: Prospective, multicenter cohort study. SETTING: Internal medicine departments in Spain. PARTICIPANTS: Inpatients >75 years with NVAF. MEASUREMENTS: We measured the thrombotic and hemorrhagic risk at admission using the CHA2DS2-VASc and HAS-BLED scales, respectively, and the nutritional risk with the controlling nutritional status (CONUT) index. We established 4 degrees of nutritional risk: null (CONUT score 0-1 point), low (2-4 points), moderate (5-8 points) and high (9-12 points). We also conducted a 1-year follow-up. RESULTS: We included 449 patients, with a mean age of 85.2(5.2) years. The nutritional risk was null for 70(15.6%) patients, low for 206 45.9%), moderate for 152(33.8%) and high for 21(4.7%). At the end of one year, 177(39.4%) patients had died. The score on the CONUT index was higher for the deceased patients (4.6 vs. 3.6, p<0.001). The CONUT score (HR, 1.076; 95%CI 1.009-1.148; p=0.025), the Charlson index (HR, 1.080; 95%CI 1.017-1.148; p=0.013) and the presence of pressure ulcers (HR, 1.700; 95%CI 1.028-2.810; p=0.039) were independently associated with increased mortality at one year of follow-up. The prescription of oral anticoagulants at discharge was associated with lower mortality (HR, 0.440; 95%CI 0.304-0.638; p<0.001). CONCLUSIONS: More than a third of elderly patients hospitalized with NVAF have a moderate to high nutritional risk. These patients have greater mortality at the end of one year.

The role of seagrass vegetation and local environmental conditions in shaping benthic bacterial and macroinvertebrate communities in a tropical coastal lagoon.

We investigated the influence of seagrass canopies on the benthic biodiversity of bacteria and macroinvertebrates in a Red Sea tropical lagoon. Changes in abundance, number of taxa and assemblage structure were analyzed in response to seagrass densities (low, SLD; high, SHD; seagrasses with algae, SA), and compared with unvegetated sediments. Biological and environmental variables were examined in these four habitats (hereafter called treatments), both in the underlaying sediments and overlaying waters, at three randomly picked locations in March 2017. Differences between treatments were more apparent in the benthic habitat than in the overlaying waters. The presence of vegetation (more than its cover) and changes in sedimentary features (grain size and metals) at local scales influenced the observed biological patterns, particularly for macroinvertebrates. Of note, the highest percentage of exclusive macroinvertebrate taxa (18% of the gamma diversity) was observed in the SHD treatment peaking in the SA for bacteria. Benthic macroinvertebrates and bacteria shared a generally low number of taxa across treatments and locations; approximately, 25% of the gamma diversity was shared among all treatments and locations for macrofauna, dropping to 11% for bacteria. Given the low overlap in the species distribution across the lagoon, sustaining the connectivity among heterogeneous soft sediment habitats appears to be essential for maintaining regional biodiversity. This study addresses a current scientific gap related to the relative contributions of vegetated and unvegetated habitats to biodiversity in tropical regions.

Visualization of gene expression in living adult Drosophila.

To identify genes involved in the patterning of adult structures, Gal4-UAS (upstream activating site) technology was used to visualize patterns of gene expression directly in living flies. A large number of Gal4 insertion lines were generated and their expression patterns were studied. In addition to identifying several characterized developmental genes, the approach revealed previously unsuspected genetic subdivisions of the thorax, which may control the disposition of pattern elements. The boundary between two of these domains coincides with localized expression of the signaling molecule wingless.

Sarcopenia, frailty, cognitive impairment and mortality in elderly patients with non-valvular atrial fibrillation. / Sarcopenia, fragilidad, deterioro cognitivo y mortalidad en pacientes ancianos con fibrilación auricular no valvular.

OBJECTIVES: To determine the prevalence of sarcopenia, frailty and cognitive impairment in elderly patients with nonvalvular atrial fibrillation (NVAF) and the factors' influence on survival. METHODS: Prospective, multicentre cohort study of patients older than 75 years with NVAF hospitalised in internal medicine departments in Spain. For each patient, we recorded the creatinine, haemoglobin and platelet levels, the scores on the CHA2DS2-VASc and HAS-BLED scales and Charlson index, as well as the use of oral anticoagulants. We measured sarcopenia with the SARC-F scale, frailty with the FRAIL scale and cognitive impairment with the Short Portable Mental State Questionnaire. We also conducted a 1-year follow-up. RESULTS: The study included 596 patients with NVAF, with a mean age of 84.9 (SD: 5.2) years. Of these, 295 (49.5%) presented sarcopenia, 305 (51.2%) presented frailty, and 251 (42.1%) presented cognitive impairment. At the end of 1year, 226 (37.9%) patients had died. Mortality was greater for the patients with sarcopenia, frailty and cognitive impairment. In the multivariate analysis, sarcopenia (HR: 1.775; 95%CI: 1.270-2.481), age, comorbidity and a history of peripheral embolism were associated with increased mortality, and the use of oral anticoagulants at discharge (HR: 0.415; 95%CI: 0.307-0.560) was associated with lower mortality. CONCLUSIONS: Sarcopenia, frailty and cognitive impairment are very common in elderly patients with NVAF and are frequently associated. Sarcopenia was associated with increased mortality.

[Preoperative workup to assess indication for laparoscopic treatment in gastroesophageal reflux disease].

INTRODUCTION AND OBJECTIVES: antireflux surgery performed by an experienced surgeon is a maintenance option for patients with well-documented gastroesophageal reflux disease (GERD). Well-documented GERD is difficult to find, as GERD is a multifactorial disease in which the gastroesophageal junction, with its special anatomical and functional components, is important. In order to examine patient preoperative workups, and their indication for surgical treatment in GERD, we retrospectively studied patients who underwent a laparoscopic antireflux procedure. METHODS: preoperative workups in patients from our health care area who underwent a laparoscopic antireflux procedure from December 1997 to February 2007 were retrospectively analyzed. Data related to epidemiological findings, symptoms, morphologic and functional evaluation, medical therapy, and indication for surgical treatment were recorded and statistically analyzed by means of a bivariate test. Differences were significant when the p value was equal to or less than 0.05. RESULTS: 100 patients (50 % female, 51.31 +/- 13.53 years of age) underwent a laparoscopic antireflux surgery after 56.47 +/- 61.33 months with symptoms. Ninety-five percent of patients had an anatomical abnormality. The pH monitoring test diagnosed three quarters of cases. The most frequent indication for GERD treatment was persistent or recurrent esophagitis despite adequate medical treatment (52 cases). CONCLUSIONS: based on our preoperative workup, as described, 100 percent of subjects were well documented and diagnosed with GERD (both non-erosive reflux disease and erosive reflux disease), and their indication for laparoscopic treatment was retrospectively assessed in 94% of cases.

Proposal for the creation of a national strategy for precision medicine in cancer: a position statement of SEOM, SEAP, and SEFH.

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational, and knowledge-related challenges. Without a national strategy, precision medicine, which will be implemented one way or another, could take place without the appropriate planning that can guarantee technical quality, equal access of all citizens to the best practices, violating the rights of patients and professionals, and jeopardizing the solvency of the healthcare system. With this paper from the Spanish Societies of Medical Oncology, Pathology, and Hospital Pharmacy, we highlight the need to institute a consensual national strategy for the development of precision medicine in our country, review the national and international context, comment on the opportunities and challenges for implementing precision medicine, and outline the objectives of a national strategy on precision medicine in cancer.

The progeny of wingless-expressing cells deliver the signal at a distance in Drosophila embryos.

Pattern formation in developing animals requires that cells exchange signals mediated by secreted proteins. How these signals spread is still unclear. It is generally assumed that they reach their target site either by diffusion or active transport (reviewed in [1] [2]). Here, we report an alternative mode of transport for Wingless (Wg), a member of the Wnt family of signaling molecules. In embryos of the fruit fly Drosophila, the wingless (wg) gene is transcribed in narrow stripes of cells abutting the source of Hedgehog protein. We found that these cells or their progeny are free to roam towards the anterior. As they do so, they no longer receive the Hedgehog signal and stop transcribing wg. The cells leaving the expression domain retain inherited Wg protein in secretory vesicles, however, and carry it forwards over a distance of up to four cell diameters. Experiments using a membrane-tethered form of Wg showed that this mechanism is sufficient to account for the normal range of Wg. Nevertheless, evidence exists that Wg can also reach distant target cells independently of protein inheritance, possibly by restricted diffusion. We suggest that both transport mechanisms operate in wild-type embryos.

Spatially multiplexed dark-field microspectrophotometry for nanoplasmonics.

Monitoring the effect of the substrate on the local surface plasmon resonance (LSPR) of metallic nanoparticles is key for deepening our understanding of light-matter interactions at the nanoscale. This coupling gives rise to shifts of the LSPR as well as changes in the scattering pattern shape. The problem requires of high-throughput techniques that present both high spatial and spectral resolution. We present here a technique, referred to as Spatially Multiplexed Micro-Spectrophotometry (SMMS), able to perform polarization-resolved spectral and spatial analysis of the scattered light over large surface areas. The SMMS technique provides three orders of magnitude faster spectroscopic analysis than conventional dark-field microspectrophotometry, with the capability for mapping the spatial distribution of the scattered light intensity with lateral resolution of 40 nm over surface areas of 0.02 mm(2). We show polarization-resolved dark-field spectral analysis of hundreds of gold nanoparticles deposited on a silicon surface. The technique allows determining the effect of the substrate on the LSPR of single nanoparticles and dimers and their scattering patterns. This is applied for rapid discrimination and counting of monomers and dimers of nanoparticles. In addition, the diameter of individual nanoparticles can be rapidly assessed with 1 nm accuracy.

How two-dimensional bending can extraordinarily stiffen thin sheets.

Curved thin sheets are ubiquitously found in nature and manmade structures from macro- to nanoscale. Within the framework of classical thin plate theory, the stiffness of thin sheets is independent of its bending state for small deflections. This assumption, however, goes against intuition. Simple experiments with a cantilever sheet made of paper show that the cantilever stiffness largely increases with small amounts of transversal curvature. We here demonstrate by using simple geometric arguments that thin sheets subject to two-dimensional bending necessarily develop internal stresses. The coupling between the internal stresses and the bending moments can increase the stiffness of the plate by several times. We develop a theory that describes the stiffness of curved thin sheets with simple equations in terms of the longitudinal and transversal curvatures. The theory predicts experimental results with a macroscopic cantilever sheet as well as numerical simulations by the finite element method. The results shed new light on plant and insect wing biomechanics and provide an easy route to engineer micro- and nanomechanical structures based on thin materials with extraordinary stiffness tunability.