The AGE reader:a non-invasive method to assess long term tissue damage

AIMS: Advanced glycation endproducts (AGEs) are sugar modified adducts which arise during non-enzymatic glycoxidative stress. These compounds may become systemically elevated in disease states, and accumulate in tissue, especially on long-lived proteins. AGEs have been implicated in various acute, and chronic diseases, stressing the need for reliable and comprehensive measuring techniques. Measurement of AGEs in tissue such as skin requires skin biopsies, which is an invasive procedure. The AGE Reader has been developed to assess skin autofluorescence (SAF) non-invasively by the fluorescent properties of several AGEs. RESULTS/CONCLUSION: Various studies have shown that SAF is a useful marker of disease processes associated with oxidative stress. It is prospectively associated with development of cardiovascular events in patients with diabetes, renal or cardiovascular disease, and it predicts diabetes, cardiovascular disease and mortality in the general population. However, when measuring SAF in individual subjects, several factors may limit the reliability of the measurement, and hamper its use as a systemic biomarker for AGEs. These include endogenous factors present in the skin that absorb emission light such as melanin in dark-skinned subjects, but also factors that lead to temporal changes in SAF such as acute diseases and strenuous physical exercise associated with glycoxidative stress. Also, exogenous factors could potentially influence SAF levels inadvertently such as nutrition, and for example the application of skin care products. This review will give an overview of the AGE Reader functionality and the intrinsic, and exogenous factors which potentially influence the SAF assessment in individual subjects

Quantification of volumetric morphometry and optical property in the cortex of human cerebellum at micrometer resolution

The surface of the human cerebellar cortex is much more tightly folded than the cerebral cortex. Volumetric analysis of cerebellar morphometry in magnetic resonance imaging studies suffers from insufficient resolution, and therefore has had limited impact on disease assessment. Automatic serial polarization-sensitive optical coherence tomography (as-PSOCT) is an emerging technique that offers the advantages of microscopic resolution and volumetric reconstruction of large-scale samples. In this study, we reconstructed multiple cubic centimeters of ex vivo human cerebellum tissue using as-PSOCT. The morphometric and optical properties of the cerebellar cortex across five subjects were quantified. While the molecular and granular layers exhibited similar mean thickness in the five subjects, the thickness varied greatly in the granular layer within subjects. Layer-specific optical property remained homogenous within individual subjects but showed higher cross-subject variability than layer thickness. High-resolution volumetric morphometry and optical property maps of human cerebellar cortex revealed by as-PSOCT have great potential to advance our understanding of cerebellar function and diseases

CC chemokine receptor 5 polymorphism in Italian patients with Behcet's disease.

Objective. To evaluate the potential role of CC chemokine receptor 5 (CCR5)Δ32 polymorphism in the susceptibility to and clinical expression of Behçet's disease (BD) in a cohort of Italian patients.Methods. One hundred and ninety-six consecutive Italian patients satisfying the ISG criteria for BD were followed up for 8 years, and 180 healthy age- and sex-matched blood donors were molecularly genotyped for the CCR5Δ32 polymorphism. A standard microlymphocytotoxicity technique was used to serotype HLA-B51. The patients were subgrouped on the basis of the presence or absence of clinical manifestations.Results. The distribution of the CCR5Δ32 genotype differed between BD patients and controls (P = 0.02). The CCR5Δ32 allele was more common in BD patients than in controls [P = 0.02, odds ratio (OR) 2.28 (95% CI 1.1, 4.8)]. Carriers of the CCR5Δ32 allele (Δ32/Δ32 + CCR5/Δ32) were significantly more common in BD patients than in controls [P = 0.02, OR 2.37 (95% CI 1.1, 5.1)]. Population-attributable risk was 7.1%. In categorizing patients according to gender, the association between CCR5Δ32 polymorphism and BD was similar in females and males (ORs 2.76 and 2.0, respectively). No significant differences were found when the frequencies of clinical manifestations were compared between CC5RΔ32 allele carriers and non-carriers.Conclusion. CCR5Δ32 polymorphism is associated with an increased susceptibility to develop BD. Chemokines may have a role in the pathophysiology of BD

The perception of professionals and users of the quality of care and respect for human rights in four outpatient care facilities of an Italian hospital during the Covid-19 pandemic

Background: During the Covid-19 pandemic, delays in providing medical services, dissatisfaction, criticism toward health workers (HW) and the risk of burnout of HW in Italy have been documented. No studies have contrasted the point of view of HW and users on the quality of care and respect for human rights in health facilities. Objective: To compare the perception of users of their satisfaction with the care provided with the perception of HW of their satisfaction with work as well as the perception of the respect of HW “s and users” human rights. Methods: The “Well-Being at work and respect for human rights questionnaire” (WWRR) was administered on a sample of users (142) and HW (154) in four outpatient health care facilities of a hospital in Sardinia, Italy. Results: Users showed higher scores than HW on their satisfaction with the care received (p < 0.0001), the perception of respect for their human rights (p < 0.0001), and availability of resources for care (p < 0.0001). The HW scores were higher than 50% of the maximum in all items, but a relatively low score was reported on the HW’s satisfaction of the resources and the respect for their rights. Conclusion: The satisfaction for care and respect for human rights in the outpatient health services was higher than expected. The relatively low score by the HWs in relation to the satisfaction with the resources and perception of respect for their human rights could be a wake-up call. The study does not involve emergency rooms, wards, or Covid units

The Rheumatology drugs for COVID-19 management: Which and when?

Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. 'Repurposing' immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patient

Why Was the Perception of Human Rights Respect and Care Satisfaction So High in Users of Italian Mental Health Services during the COVID-19 Pandemic?

The aim of this study was to compare users’ and mental health workers’ (MHW) perception of respect of human rights and job/care satisfaction in mental health services in Italy during the COVID-19 pandemic. A sample of users and MHW of Sardinia, Italy, fulfilled the “WellBeing at work and respect for human rights questionnaire” (WWRR). The study included 240 MHW and 200 users. Users showed a higher level of satisfaction of care than MHW of work, and a higher perception of the satisfaction of users and human rights respected for health workers. Both user and MHW responses were about 85% of the maximum score, except for satisfaction with resources. Responses were higher for users, but users and MHW both showed high levels of satisfaction. In previous surveys, MHW of Sardinia showed higher scores in all items of WWRR, except for satisfaction with resources, compared with workers from other health sectors of the same region, and with MHW from other countries. The low score for satisfaction with resources (in users and staff) is consistent with a progressive impoverishment of resources for mental health care in Italy. The study, although confirming the validity of the Italian model, fully oriented towards community, sets off an alarm bell on the risks resulting from the decrease in resources

[18F]Sodium Fluoride PET has the potential to identify active formation of calcinosis cutis in limited cutaneous systemic sclerosis

OBJECTIVES: Calcinosis cutis affects 20-40% of patients with systemic sclerosis (SSc). When calcinosis cutis becomes clinically apparent, it is irreversible in most cases. Detection of active calcification formation might allow early disease-modifying interventions. We assessed the feasibility of visualizing active calcifications using [18F]Sodium Fluoride ([18F]NaF) PET/low-dose CT (LDCT) in SSc patients with calcinosis cutis. METHODS: In this cross-sectional, observational pilot study patients underwent a whole body [18F]NaF PET/LDCT. All patients met the 2013 ACR/EULAR SSc criteria and had clinically detectable calcinosis cutis. (Sub)cutaneous calcifications were described by three investigators. RESULTS: Nine female patients were included (median age 59.0 years [IQR 51.5-70.5]). [18F]NaF uptake was mostly visible in the fingers (n=7) and knees (n=5). [18F]NaF PET showed calcifications in the fingers of 3 patients where calcifications were undetected on LDCT and in the clinic. Ninety-seven percent of [18F]NaF positive lesions was visible on LDCT. Of all lesions visible on LDCT, 70% was also visible on [18F]NaF PET. CONCLUSION: Imaging of active calcifications in SSc is feasible using [18F]NaF PET/LDCT. Seventy percent of calcifications on LDCT were [18F]NaF PET positive. Although these findings require replication, [18F]NaF PET/LDCT may detect active calcification formation, being potentially suitable for early disease-modifying interventions

The Role of Hyperbaric Oxygen Therapy in Orthopedics and Rheumatological Diseases

Hyperbaric oxygen therapy (HBOT) has been investigated as a primary/adjunctive treatment for a number of injuries and medical conditions including traumatic ischemia, necrotizing soft tissue injuries, non-healing ulcers and osteoradionecrosis, but the results are controversial. There is insufficient evidence to support or reject the use of HBOT to quicken healing or to treat the established non-union of fractures. However, in patients with fibromyalgia, HBOT reduces brain activity in the posterior cortex and increases it in the frontal, cingulate, medial temporal and cerebellar cortices, thus leading to beneficial changes in brain areas that are known to function abnormally. Moreover, the amelioration of pain induced by HBOT significantly decreases the consumption of analgesic medications. In addition, HBOT has anti-inflammatory and oxygenatory effects in patients with primary or secondary vasculitis. This review analyzes the efficacy and limitations of HBOT in orthopedic and rheumatologic patients

Ferritin and C-reactive protein are predictive biomarkers of mortality and macrophage activation syndrome in adult onset Still's disease. Analysis of the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort

Objective To assess the predictive role of ferritin and C-reactive protein (CRP) on occurrence of macrophage activation syndrome (MAS) and mortality in patients with adult onset Still's disease (AOSD), a rare and severe disease, included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort. Methods The predictive role, at the time of diagnosis, of serum levels of ferritin and CRP on occurrence of MAS and mortality, was evaluated by logistic regression analyses and receiveroperating characteristic (ROC) curves were built to identify patients at high risk of MAS and mortality, respectively. Results In assessed 147 patients with AOSD, levels of ferritin were predictive of MAS (OR: 1.971; P: 0.002; CI 95%: 1.280-3.035). The ROC curve showed that the best cut-off for ferritin was 1225 ng/ml in predicting MAS (sensitivity 88%; specificity 57%). Levels of CRP were predictive of mortality in these patients (OR: 2.155; P: 0.007; CI 95%: 1.228-3.783). The ROC curve showed that the best cut-off for CRP was 68.7 mg/L in predicting mortality (sensitivity 80%; specificity of 65%). Conclusions We reported the predictive role of ferritin and CRP on MAS and mortality, respectively, in a large cohort of patients with AOSD, identifying subsets at higher risk of poor prognosis. Considering that the analysis of CRP and ferritin is widely available, these results could be readily transferable into clinical practice, thus improving the management of patients with AOSD

Nuevo prototipo de máquina frigorífica de absorción de LiBr-H₂O de simple y doble efecto con absorbedor adiabático refrigerado por aire de alta eficiencia : descripción, simulación y resultados experimentales

Due to unsustainable growth of air conditioning market, a great interest in solar cooling technologies has emerged. The coincidence between availability of solar irradiation and peaks of cooling demand makes solar cooling a very attractive option to replace conventional refrigeration machines based on electricity. What is more, solar cooling systems normally use natural refrigerants that are not harmful to the environment. However, an improvement of the current technology is needed for solar cooling systems to compete with electricity‐powered air conditioning systems. In this work, a novel air‐cooled single–double‐effect LiBr/H₂O absorption prototype is proposed as a solution to improve the viability of solar cooling systems. This prototype presents the following distinguishing features: firstly, it is directly air‐cooled, which means that no cooling tower is needed; secondly, it is made up by compact heat exchangers, which allows for a reduced size of about 1 m₃; thirdly, it incorporates an adiabatic absorber operating with flat‐fan solution sheets, which permits the working solution not to crystallize at high ambient temperatures; lastly, it can be powered by solar heat in its single‐effect mode (4.5 kW), or by an alternative source such as fuel or waste heat in its double‐effect stage (7 kW). In this way, 100% of the cooling demand may be supplied by a single absorption machine using solar energy as far as possible or, when it is not available, efficiently utilizing a fuel or even waste heat, for instance in a trigeneration system. This thesis includes a detailed description of that single–double‐effect absorption prototype as well as the fundamentals for its numerical simulation. Likewise, experimental results from a testing campaign carried out in Madrid during 2010 are presented and discussed. A solar facility with evacuated flat‐plate collectors was used to test the single-effect operation mode of the prototype. In turn, the double‐effect stage was fired by a thermal oil facility with electrical resistances. As relevant results of the whole experimental campaign it is worth mentioning that the single‐effect stage was able to work with COP values around 0.6, whereas the double‐effect mode permitted to achieve values of about 1.0. The chilled water temperatures mostly ranged between 14°C and 16°C in single‐effect operation mode, while they were around 12°C for the double‐effect stage. Besides, it is highly noteworthy that after some 125 hours of operation under a wide range of conditions (outdoor temperatures up to 39.5°C), no solution crystallization was noticed. On the other hand, this work includes an in‐depth description of the absorber assembled in the single–double‐effect prototype. Furthermore, a mathematical model is developed for simulation of air‐cooled flat‐fan sheets adiabatic absorbers. As far as we know, there is not any numerical modeling for this kind of absorbers in the literature. Based on that model, which was as well experimentally validated in this study, the capacity of the prototype absorber is optimized as a function of the energy consumption of its ancillary equipment (solution pump and fan). Finally, the positive results derived from this work may be regarded as an important contribution to the development of air‐cooled LiBr/H₂O absorption technology. Even though a few improvements in the prototype are still required, it seems that the proposed system represents a feasible alternative to overcome some of the major obstacles concerning solar air conditioning. -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------La actual situación de insostenibilidad en el mercado de la climatización ha motivado un gran interés por la refrigeración solar como alternativa al uso de máquinas eléctricas. El hecho de que las horas de máxima radiación solar coincidan con los momentos de mayor demanda de frío en los edificios, hace que estos sistemas sean especialmente indicados para sustituir a los equipos convencionales de aire acondicionado. Además, hay que añadir que esta tecnología normalmente utiliza refrigerantes naturales que no son dañinos para el medio ambiente. Sin embargo, los sistemas actuales de refrigeración solar necesitan una mejora sustancial para poder competir directamente con los aparatos tradicionales de climatización. Como una posible solución para mejorar la viabilidad de los sistemas de refrigeración solar, en este trabajo se presenta un nuevo prototipo de máquina de absorción de LiBr/H₂O que integra los ciclos de simple y doble efecto en una misma unidad. Las principales características que hacen de este prototipo una novedad tecnológica son las siguientes: en primer lugar, se trata de una máquina directamente condensada por aire, eliminando así la necesidad de instalar torres de refrigeración; en segundo lugar, el prototipo está básicamente formado por intercambiadores de calor compactos, con lo que se alcanza un tamaño final de máquina muy reducido, aproximadamente 1 m3; en tercer lugar, el prototipo incorpora un absorbedor adiabático con láminas planas que evita que la disolución cristalice a altas temperaturas ; por último, la máquina puede funcionar como una unidad de simple efecto (4.5 kW), alimentada en este caso por energía solar, o como una unidad de doble efecto (7 kW), quemando combustibles o utilizando calor residual. De este modo, se podría llegar cubrir el 100% de la demanda de refrigeración con una sola unidad que saca el máximo partido a la energía solar y, cuando ésta no es suficiente, utiliza eficientemente combustibles o incluso el calor residual procedente de otros procesos, por ejemplo en una planta de trigeneración. En esta tesis doctoral se incluye una descripción detallada del prototipo de simple y doble efecto así como los fundamentos teóricos para su simulación numérica. Asimismo, se presentan y discuten los resultados experimentales obtenidos durante una campaña de ensayos llevada a cabo en Madrid durante el año 2010. Para probar el funcionamiento del prototipo como máquina de absorción de simple efecto se ha utilizado una instalación solar con colectores planos de vacío. En cambio, para ensayar el prototipo como máquina de doble efecto se ha utilizado un aceite térmico como fuente de energía. Como resultados destacados de la campaña de experimentación cabe mencionar que los valores del COP se movieron entorno a 0.6 en simple efecto y alrededor de 1.0 en doble efecto. A su vez, se alcanzaron temperaturas de agua fría entre 14°C y 16°C para el simple efecto y de aproximadamente 12°C para el doble efecto. Además, es de gran relevancia el hecho de que, después de unas 125 horas de funcionamiento bajo condiciones de trabajo muy diferentes (hasta 39.5°C de temperatura exterior), la disolución de LiBr/H₂O no se haya cristalizado en ningún momento. Por otra parte, este trabajo incluye una descripción detallada del absorbedor instalado en el prototipo. Asimismo, se ha desarrollado un modelo matemático para simular absorbedores adiabáticos de láminas directamente refrigerados por aire. Por lo que sabemos, hasta el momento no se ha publicado ninguna modelización numérica para este tipo de absorbedores. Tomando como referencia el modelo propuesto, que también ha sido validado experimentalmente en este estudio, se ha realizado una optimización de la capacidad del absorbedor del prototipo en función del consumo energético de sus equipos auxiliares (bomba de disolución y ventilador). Por último, los buenos resultados obtenidos con este prototipo nos hacen pensar que este trabajo representa una contribución importante al desarrollo de las máquinas de absorción de LiBr/H₂O refrigeradas por aire. A pesar de que el prototipo todavía no está totalmente optimizado, con él se ha demostrado que la tecnología propuesta en esta tesis doctoral constituye una alternativa viable para superar algunos de los principales problemas relacionados con la refrigeración solar