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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Blood contains a range of protein biomarkers that could be used in the early detection of disease. To achieve this, however, requires sensors capable of detecting (with high reproducibility) biomarkers at concentrations one million times lower than the concentration of the other blood proteins. Here, we show that a sandwich assay that combines mechanical and optoplasmonic transduction can detect cancer biomarkers in serum at ultralow concentrations. A biomarker is first recognized by a surface-anchored antibody and then by an antibody in solution that identifies a free region of the captured biomarker. This second antibody is tethered to a gold nanoparticle that acts as a mass and plasmonic label; the two signatures are detected by means of a silicon cantilever that serves as a mechanical resonator for 'weighing' the mass of the captured nanoparticles and as an optical cavity that boosts the plasmonic signal from the nanoparticles. The capabilities of the approach are illustrated with two cancer biomarkers: the carcinoembryonic antigen and the prostate specific antigen, which are currently in clinical use for the diagnosis, monitoring and prognosis of colon and prostate cancer, respectively. A detection limit of 1 × 10−16 g ml−1 in serum is achieved with both biomarkers, which is at least seven orders of magnitude lower than that achieved in routine clinical practice. Moreover, the rate of false positives and false negatives at this concentration is extremely low, ∼10−4. [ABSTRACT FROM AUTHOR]

A series of dust pollen samples was collected along N-S transects in east China (18°N to 53°N latitudes). Sample sites extend from the cold-temperate zone in the north to the tropical region in the south. Pollen taxa characterize each region and reflect the natural and devastated vegetation as well as corresponding climatic zones. The quantitative pollen data can be used to estimate the spatial distribution of planted and introduced species. Valuable information of human disturbance of the natural forest is evaluated by quantitative comparison between dust pollen and in-situ pollen of protected forest. In addition, percentages of grass pollen vary regularly from north to south that is consistent with spatial distribution of net primary productivity in east China. Among all grasses, Artemisia and the Gramineae carry the clearest signal: their ratio increases northwards and therefore represent a suitable and convenient tool for palaeoclimate reconstructions. [ABSTRACT FROM AUTHOR]

The mechanisms involved in the regulation of mitochondrial DNA (mtDNA) replication, a process that is crucial for mitochondrial biogenesis, are not well understood. In this study, we evaluate the role of DNA polymerase γ (pol γ), the key enzyme in mtDNA replication, in both Drosophila cell culture and in developing flies. We report that overexpression of the pol γ catalytic subunit (pol γ-α) in cultured Schneider cells does not alter either the amount of mtDNA or the growth rate of the culture. The polypeptide is properly targeted to mitochondria, yet the large excess of pol γ-α does not interfere with mtDNA replication under these conditions where the endogenous polypeptide is apparently present in amounts that exceed of the demand for its function in the cell. In striking contrast, overexpression of pol γ-α at the same level in transgenic flies interferes with the mtDNA replication process, presumably by altering the mechanism of DNA synthesis, suggesting differential requirements for, and/or regulation of, mtDNA replication in Drosophila cell culture versus the developing organism. Overexpression of pol γ-α in transgenic flies produces a significant depletion of mtDNA that causes a broad variety of phenotypic effects. These alterations range from pupal lethality to moderate morphological abnormalities in adults, depending on the level and temporal pattern of overexpression. Our results demonstrate that although cells may tolerate a variable amount of the pol γ catalytic subunit under some conditions, its level may be critical in the context of the whole organism. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic cholecystectomy (LC) has become firmly established as a procedure of choice for gallstone disease. The procedure usually necessitates general anaesthesia and endotracheal intubation to prevent aspiration and respiratory embarrassment secondary to the induction of pneumoperitoneum. There is a paucity of data in the literature on the procedure being performed under regional (epidural) anaesthesia, especially in patients with coexisting pulmonary disease and pregnancy, who are deemed high risk for general anaesthesia. We report our preliminary experience with LC using epidural anaesthesia in patients with chronic obstructive pulmonary disease (COPD). Methods: We performed LC in six patients (one man and five women), with a median age of 56 years (range, 38–74), under epidural anaesthesia over an 8-month period. All patients were ASA grade III/IV and the mean FEV1/FVC was 0.52 (range, 0.4–0.68), due to chronic asthma (two cases) and COPD (four cases). They were admitted a day prior to surgery for pulmonary function tests, nebulisers, and chest physiotherapy. An epidural catheter was introduced at T10/11 intervertebral space, and a bolus of 0.5% Bupivacaine was administered. Depending on the patient's pain threshold and the segmental level of analgesia achieved, incremental doses of 2 ml of 0.5% Bupivacaine along with boluses of intravenous 100 mcg Alfentanil was given to each patient. The patients were breathing spontaneously. No nasogastric tube was inserted, and a low-pressure (10 mmHg) pneumoperitoneum was created. LC was performed according to the standard technique. Results: All the patients tolerated the procedure well and made an uneventful postoperative recovery. Median operating time was 50 min; average length of hospital stay was 2.5 days (range, 2–4). The epidural catheter was removed the morning after the operation. Only one patient required postoperative opioid analgesia. Two patients complained of persistent shoulder tip pain during surgery and required intraoperative analgesia (Alfentanil). There was no change in the patient's cardiorespiratory status, including pO2 and pCO2, and no complications occurred either intra- or postoperatively. Conclusions: LC can be performed safely under epidural anaesthesia in patients with severe COPD. Intraoperative shoulder tip or abdominal pain does not seem to be a major deterrent and can be effectively controlled with small doses of opioid analgesia. [ABSTRACT FROM AUTHOR]

Abstract. The tapping-mode operation of a scanning force microscope represents an intermediate situation between contact and noncontact regimes. Its rapid development and expansion are due to lateral force minimization and its ability to give phase-contrast images of heterogeneous surfaces. Here, we calculate the phase shift between the cantilever excitation and its response as a function of the sample mechanical properties, tip-sample separation, and adhesion forces. We show that the phase shift that gives rise to phase-contrast images is associated with tip-sample interactions that involve energy dissipation such as adhesion energy hysteresis and viscoelasticity. Experimental phase-shift measurements performed on mica surfaces support the conclusions of the model. [ABSTRACT FROM AUTHOR]