Vitamin D Receptor From VSMCs Regulates Vascular Calcification During CKD: A Potential Role for miR-145a.

BACKGROUND: Vascular calcification (VC) is a highly prevalent complication of chronic kidney disease (CKD) and is associated with the higher morbidity-mortality of patients with CKD. VDR (vitamin D receptor) has been proposed to play a role in the osteoblastic differentiation of vascular smooth muscle cells (VSMCs), but the involvement of vitamin D in VC associated to CKD is controversial. Our aim was to determine the role of local vitamin D signaling in VSMCs during CKD-induced VC. METHODS: We used epigastric arteries from CKD-affected patients and individuals with normal renal function, alongside an experimental model of CKD-induced VC in mice with conditional deletion of VDR in VSMC. In vitro, experiments in VSMC with or without VDR incubated in calcification media were also used. RESULTS: CKD-affected patients and mice with CKD showed an increase in VC, together with increased arterial expression of VDR compared with controls with normal renal function. Conditional gene silencing of VDR in VSMCs led to a significant decrease of VC in the mouse model of CKD, despite similar levels of renal impairment and serum calcium and phosphate levels. This was accompanied by lower arterial expression of OPN (osteopontin) and lamin A and higher expression of SOST (sclerostin). Furthermore, CKD-affected mice showed a reduction of miR-145a expression in calcified arteries, which was significantly recovered in animals with deletion of VDR in VSMC. In vitro, the absence of VDR prevented VC, inhibited the increase of OPN, and reestablished the expression of miR-145a. Forced expression of miR-145a in vitro in VDRwt VSMCs blunted VC and decreased OPN levels. CONCLUSIONS: Our study provides evidence proving that inhibition of local VDR signaling in VSMCs could prevent VC in CKD and indicates a possible role for miR-145a in this process.

Cumulative tobacco consumption has a dose-dependent effect on atheromatosis burden and improves severe atheromatosis prediction in asymptomatic middle-aged individuals: The ILERVAS study.

BACKGROUND AND AIMS: Sex-specific impact of cumulative tobacco consumption (CTC) on atheromatosis extension and total plaque area remains unknown. We aimed to determine the impact of CTC in atheromatosis localization and burden. METHODS: We performed a cross-sectional analysis in 8330 asymptomatic middle-aged individuals. 12-territory vascular ultrasounds in carotid and femoral arteries were performed to detect atheromatous plaque presence and to measure total plaque area. Adjusted regressions and conditional predictions by smoking habit or CTC (stratified in terciles as low (≤13.53), medium (13.54-29.3), and high (>29.3 packs-year)) were calculated. Severe atheromatosis (SA, ≥3 territories with atheroma plaque) was predicted with the Systematic COronary Risk Evaluation 2 (SCORE2) model. The improvement of SA prediction after adding CTC was evaluated. RESULTS: CTC was associated with an increased risk of atheromatosis, stronger in femoral than in carotid artery, but similar in both sexes. A dose-dependent effect of CTC on the number of territories with atheroma plaque and total plaque area was observed. Addition of CTC to the SCORE2 showed a higher sensitivity, accuracy, and negative predictive value in males, and a higher specificity and positive predictive value in females. In both sexes, the new SCORE2-CTC model showed a significant increase in AUC (males: 0.033, females: 0.038), and in the integrated discrimination index (males: 0.072; females: 0.058, p < 0.001). Age and CTC were the most important clinical predictors of SA in both sexes. CONCLUSIONS: CTC shows a dose-dependent association with atheromatosis burden, impacts more strongly in femoral arteries, and improves SA prediction.

Development and Validation of a Personalized, Sex-Specific Prediction Algorithm of Severe Atheromatosis in Middle-Aged Asymptomatic Individuals: The ILERVAS Study.

Background: Although European guidelines recommend vascular ultrasound for the assessment of cardiovascular risk in low-to-moderate risk individuals, no algorithm properly identifies patients who could benefit from it. The aim of this study is to develop a sex-specific algorithm to identify those patients, especially women who are usually underdiagnosed. Methods: Clinical, anthropometrical, and biochemical data were combined with a 12-territory vascular ultrasound to predict severe atheromatosis (SA: ≥ 3 territories with plaque). A Personalized Algorithm for Severe Atheromatosis Prediction (PASAP-ILERVAS) was obtained by machine learning. Models were trained in the ILERVAS cohort (n = 8,330; 51% women) and validated in the control subpopulation of the NEFRONA cohort (n = 559; 47% women). Performance was compared to the Systematic COronary Risk Evaluation (SCORE) model. Results: The PASAP-ILERVAS is a sex-specific, easy-to-interpret predictive model that stratifies individuals according to their risk of SA in low, intermediate, or high risk. New clinical predictors beyond traditional factors were uncovered. In low- and high-risk (L&H-risk) men, the net reclassification index (NRI) was 0.044 (95% CI: 0.020-0.068), and the integrated discrimination index (IDI) was 0.038 (95% CI: 0.029-0.048) compared to the SCORE. In L&H-risk women, PASAP-ILERVAS showed a significant increase in the area under the curve (AUC, 0.074 (95% CI: 0.062-0.087), p-value: < 0.001), an NRI of 0.193 (95% CI: 0.162-0.224), and an IDI of 0.119 (95% CI: 0.109-0.129). Conclusion: The PASAP-ILERVAS improves SA prediction, especially in women. Thus, it could reduce the number of unnecessary complementary explorations selecting patients for a further imaging study within the intermediate risk group, increasing cost-effectiveness and optimizing health resources. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03228459].

Actividad física, condición física y calidad de vida en los adultos mayores. Revisión sistemática / Physical activity, physical condition and quality of life in older adults. Systematic review

Introducción: El envejecimiento de la población junto al sedentarismo, puede ocasionar un deterioro funcional que conduciría a la disminución de la condición física y de la calidad de vida. La promoción del envejecimiento activo puede mejorar la calidad de vida y la condición física de nuestros mayores. Objetivo: Evaluar la evidencia científica disponible sobre el efecto de la actividad física en los mayores, en términos de calidad de vida, condición física y mantenimiento de la independencia funcional. Material y método: Revisión sistemática en las bases de datos WOS, SCOPUS y PubMed. Selección de artículos: Se incluyeron estudios de intervención que evaluaban la calidad de vida y capacidad funcional de los adultos mayores. Los estudios fueron evaluados según la calidad metodológica con la escala PEDro. Resultados: Se encontraron 1331 artículos, de los que se incluyeron 17. Las intervenciones incluyeron ejercicios de resistencia, fuerza, equilibrio, coordinación y velocidad de la marcha. Los hallazgos principales indicaron que un mayor índice de actividad física se relacionó con un menor deterioro de las funciones físicas y cognitivas de los mayores y, por lo tanto, con una mejor calidad de vida. Conclusiones: Un estilo de vida activo se asocia a una mejor calidad de vida, mejor condición física y mantenimiento de la independencia funcional. Serían convenientes otros estudios, con una mayor homogeneidad en los instrumentos de recogida de datos, con mayor frecuencia de intervenciones, para definir los programas de ejercicios más adecuados y para incrementar la evidencia científica.(AU)

Background: The aging of the population together with sedentary lifestyle, can cause a functional deterioration that leads to the decrease of physical condition and quality of life. Promoting active aging can improve the quality of life and physical condition of our elders. Objective: This work aims to investigate the available scientific evidence on the effect of physical activity in older adults, in terms of quality of life, physical condition, and maintenance of functional independence. Material and method: A systematic review was performed in the WOS, SCOPUS and PubMed databases. Selection of articles: Intervention studies evaluating the quality of life and functional capacity of older adults were included. The studies were evaluated according to methodological quality with the PEDro scale. Results: 1331 articles were found, of which 17 were included. Interventions included resistance, strength, balance, coordination, and gait speed exercises. The main findings indicated that a higher rate of physical activity was associated with less impairment of physical and cognitive functions in older adults and, therefore, with a better quality of life. Conclusions: an active lifestyle is associated with a better quality of life, better physical condition and maintenance of functional independence. Other studies, with greater homogeneity in the data collection instruments, with greater frequency of interventions, would be convenient to define the most appropriate exercise programs and to increase the scientific evidence.(AU)

Magnesium Levels Modify the Effect of Lipid Parameters on Carotid Intima Media Thickness.

Classical risk factors of atherosclerosis in the general population show paradoxical effects in chronic kidney disease (CKD) patients. Thus, low low-density lipoprotein (LDL) cholesterol levels have been associated with worse cardiovascular outcomes. Magnesium (Mg) is a divalent cation whose homeostasis is altered in CKD. Furthermore, Mg levels have been associated with cardiovascular health. The present study aims to understand the relationships of Mg and lipid parameters with atherosclerosis in CKD. In this analysis, 1754 participants from the Observatorio Nacional de Atherosclerosis en Nefrologia (NEFRONA) cohort were included. Carotid intima media thickness (cIMT) was determined in six arterial territories, and associated factors were investigated by linear regression. cIMT correlated positively with being male, Caucasian, a smoker, diabetic, hypertensive, dyslipidemic and with increased age, BMI, and triglyceride levels, and negatively with levels of HDL cholesterol. First-order interactions in linear regression analysis showed that Mg was an effect modifier on the influence of lipidic parameters. Thus, cIMT predicted values were higher when triglycerides or LDL levels were high and Mg levels were low. On the contrary, when Mg levels were high, this effect disappeared. In conclusion, Mg acts as an effect modifier between lipidic parameters and atherosclerotic cardiovascular disease. Therefore, Mg levels, together with lipidic parameters, should be taken into account when assessing atherosclerotic risk.

Disseminated cytomegalovirus disease after bendamustine: a case report and analysis of circulating B- and T-cell subsets.

BACKGROUND: Bendamustine, used for the treatment of indolent B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia, is known to cause prolonged myelosuppression and lymphocytopenia and has been associated with the risk of developing serious and fatal infections. While reports of localized CMV infections in asymptomatic patients exist, disseminated CMV disease has not been described. CASE PRESENTATION: We report the first case of disseminated CMV infection in a 75-year-old male diagnosed with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with massive bone marrow infiltration. Despite 6-cycle R-bendamustine chemotherapy resulted in a good partial response, the patient developed persistent fever and severe weight loss. Analysis of cerebrospinal fluid and peripheral blood revealed the presence of CMV-DNA, while the fundus oculi examination revealed bilateral CMV retinitis. Treatment with induction and maintenance drugs was complicated by neutropenia and deterioration of renal function with electrolyte imbalance. From an immunological standpoint, we observed a profound imbalances in phenotype and function of B- and T-cell subsets, with a high proportion of circulating total, activated CD69+ and CD80+ B-cells, a low γ/δ T-cell frequency with a high proportion of CD69- and CD38-expressing cells, and hyperactivated/exhausted CD4+ and CD8+ T-cell phenotypes unable to face CMV challenge. CONCLUSIONS: We hereby describe a severe form of disseminated CMV disease after R-bendamustine treatment. Our observations strongly support the careful clinical monitoring of CMV reactivation/infection in oncologic patients undergoing this therapeutic regimen.

Light-trapping in photon enhanced thermionic emitters.

A series of photonic crystal structures are optimized for a photon enhanced thermionic emitter. With realistic parameter values to describe a p-type GaAs device we find an efficiency above 10%. The light-trapping structures increases the performance by 2% over an optimal bilayer anti-reflective coating. We find a device efficiency very close to the case of a Lambertian absorber, but below its maximum performance. To prevent an efficiency below 10% the vacuum gap must be dimensioned according to the concentration factor of the solar irradiance.

Optically triggered infrared photodetector.

We demonstrate a new class of semiconductor device: the optically triggered infrared photodetector (OTIP). This photodetector is based on a new physical principle that allows the detection of infrared light to be switched ON and OFF by means of an external light. Our experimental device, fabricated using InAs/AlGaAs quantum-dot technology, demonstrates normal incidence infrared detection in the 2-6 µm range. The detection is optically triggered by a 590 nm light-emitting diode. Furthermore, the detection gain is achieved in our device without an increase of the noise level. The novel characteristics of OTIPs open up new possibilities for third generation infrared imaging systems ( Rogalski, A.; Antoszewski, J.; Faraone, L. J. Appl. Phys. 2009, 105 (9), 091101).

Interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in intensive care units: an interrupted time series study and cluster randomised trial.

BACKGROUND: Intensive care units (ICUs) are high-risk areas for transmission of antimicrobial-resistant bacteria, but no controlled study has tested the effect of rapid screening and isolation of carriers on transmission in settings with best-standard precautions. We assessed interventions to reduce colonisation and transmission of antimicrobial-resistant bacteria in European ICUs. METHODS: We did this study in three phases at 13 ICUs. After a 6 month baseline period (phase 1), we did an interrupted time series study of universal chlorhexidine body-washing combined with hand hygiene improvement for 6 months (phase 2), followed by a 12-15 month cluster randomised trial (phase 3). ICUs were randomly assigned by computer generated randomisation schedule to either conventional screening (chromogenic screening for meticillin-resistant Staphylococcus aureus [MRSA] and vancomycin-resistant enterococci [VRE]) or rapid screening (PCR testing for MRSA and VRE and chromogenic screening for highly resistant Enterobacteriaceae [HRE]); with contact precautions for identified carriers. The primary outcome was acquisition of resistant bacteria per 100 patient-days at risk, for which we calculated step changes and changes in trends after the introduction of each intervention. We assessed acquisition by microbiological surveillance and analysed it with a multilevel Poisson segmented regression model. We compared screening groups with a likelihood ratio test that combined step changes and changes to trend. This study is registered with ClinicalTrials.gov, number NCT00976638. FINDINGS: Seven ICUs were assigned to rapid screening and six to conventional screening. Mean hand hygiene compliance improved from 52% in phase 1 to 69% in phase 2, and 77% in phase 3. Median proportions of patients receiving chlorhexidine body-washing increased from 0% to 100% at the start of phase 2. For trends in acquisition of antimicrobial-resistant bacteria, weekly incidence rate ratio (IRR) was 0·976 (0·954-0·999) for phase 2 and 1·015 (0·998-1·032) for phase 3. For step changes, weekly IRR was 0·955 (0·676-1·348) for phase 2 and 0·634 (0·349-1·153) for phase 3. The decrease in trend in phase 2 was largely caused by changes in acquisition of MRSA (weekly IRR 0·925, 95% CI 0·890-0·962). Acquisition was lower in the conventional screening group than in the rapid screening group, but did not differ significantly (p=0·06). INTERPRETATION: Improved hand hygiene plus unit-wide chlorhexidine body-washing reduced acquisition of antimicrobial-resistant bacteria, particularly MRSA. In the context of a sustained high level of compliance to hand hygiene and chlorhexidine bathings, screening and isolation of carriers do not reduce acquisition rates of multidrug-resistant bacteria, whether or not screening is done with rapid testing or conventional testing. FUNDING: European Commission.

Self-organized colloidal quantum dots and metal nanoparticles for plasmon-enhanced intermediate-band solar cells.

A colloidal deposition technique is presented to construct long-range ordered hybrid arrays of self-assembled quantum dots and metal nanoparticles. Quantum dots are promising for novel opto-electronic devices but, in most cases, their optical transitions of interest lack sufficient light absorption to provide a significant impact in their implementation. A potential solution is to couple the dots with localized plasmons in metal nanoparticles. The extreme confinement of light in the near-field produced by the nanoparticles can potentially boost the absorption in the quantum dots by up to two orders of magnitude.In this work, light extinction measurements are employed to probe the plasmon resonance of spherical gold nanoparticles in lead sulfide colloidal quantum dots and amorphous silicon thin-films. Mie theory computations are used to analyze the experimental results and determine the absorption enhancement that can be generated by the highly intense near-field produced in the vicinity of the gold nanoparticles at their surface plasmon resonance.The results presented here are of interest for the development of plasmon-enhanced colloidal nanostructured photovoltaic materials, such as colloidal quantum dot intermediate-band solar cells.

Nanoimprinted diffraction gratings for crystalline silicon solar cells: implementation, characterization and simulation.

Light trapping is becoming of increasing importance in crystalline silicon solar cells as thinner wafers are used to reduce costs. In this work, we report on light trapping by rear-side diffraction gratings produced by nano-imprint lithography using interference lithography as the mastering technology. Gratings fabricated on crystalline silicon wafers are shown to provide significant absorption enhancements. Through a combination of optical measurement and simulation, it is shown that the crossed grating provides better absorption enhancement than the linear grating, and that the parasitic reflector absorption is reduced by planarizing the rear reflector, leading to an increase in the useful absorption in the silicon. Finally, electro-optical simulations are performed of solar cells employing the fabricated grating structures to estimate efficiency enhancement potential.

Malignant conjunctival T cell lymphoma diagnosed by punch biopsy as a primary manifestation of systemic cancer.

This report documents a case of T cell lymphoma manifesting only with a conjunctival mass. A 67-year-old man underwent a diagnostic punch biopsy, histopathological examination, and immunohistochemical study for a pink-yellow colored mass infiltrating the bulbar conjunctiva in the lower fornix of the eyelid. A biopsy specimen of the conjunctival mass was found histopathologically to be a malignant T cell lymphoma. Systemic involvement was diagnosed within four weeks after the initial diagnosis by computed tomography, showing evidence of extension at the level of the ethmoidal cells, optic nerve, periorbital tissue, and pancreas. T cell lymphoma of the conjunctiva as a primary manifestation of systemic cancer is an uncommon entity. Punch biopsy may be the first diagnostic pathway useful to initiate a search for systemic involvement of a malignant lymphoid tumor of T cell lineage.

Light concentration in the near-field of dielectric spheroidal particles with mesoscopic sizes.

This paper presents a numerical study of the light focusing properties of dielectric spheroids with sizes comparable to the illuminating wavelength. An analytical separation-of-variables method is used to determine the electric field distribution inside and in the near-field outside the particles. An optimization algorithm was implemented in the method to determine the particles' physical parameters that maximize the forward scattered light in the near-field region. It is found that such scatterers can exhibit pronounced electric intensity enhancement (above 100 times the incident intensity) in their close vicinity, or along wide focal regions extending to 10 times the wavelength. The results reveal the potential of wavelength-sized spheroids to manipulate light beyond the limitations of macroscopic geometrical optics. This can be of interest for several applications, such as light management in photovoltaics.

The intermediate band solar cell: progress toward the realization of an attractive concept.

The intermediate band (IB) solar cell has been proposed to increase the current of solar cells while at the same time preserving the output voltage in order to produce an efficiency that ideally is above the limit established by Shockley and Queisser in 1961. The concept is described and the present realizations and acquired understanding are explained. Quantum dots are used to make the cells but the efficiencies that have been achieved so far are not yet satisfactory. Possible ways to overcome the issues involved are depicted. Alternatively, and against early predictions, IB alloys have been prepared and cells that undoubtedly display the IB behavior have been fabricated, although their efficiency is still low. Full development of this concept is not trivial but it is expected that once the development of IB solar cells is fully mastered, IB solar cells should be able to operate in tandem in concentrators with very high efficiencies or as thin cells at low cost with efficiencies above the present ones.

Surveillance of arbovirus infections in the Atlantic Forest Region state of Sao Paulo, Brazil: I. detection of hemagglutination-inhibiting antibodies in wild birds between 1978 and 1990

Apresentam-se os resultados referentes a anticorpos para arbovirus em aves silvestres capturadas, periodicamente, de janeiro de 1978 a dezembro de 1990, nos municipios de Salesopolis (Estacao de Casa Grande); Itapetininga e municipios do Vale do Ribeira, considerando-se os diferentes ambientes de captura. Plasmas foram examinados, por testes de inibicao de hemaglutinacao (IH). Considerou-se apenas as reacoes monotipicas, com excecao de duas reacoes heterotipicas, onde ocorreu uma diferenca de titulo significativa para um determinado virus de um mesmo grupo antigenico. Em um total de 39.911 aves, foram encontradas 269 aves pertencentes a 66 especies e 22 familias, com reacao monotipica para os virus...