Pulmonary tuberculosis followed by sarcoidosis in an HIV-infected patient: a case report and a simplified diagnostic flowchart for diagnosis and treatment of sarcoidosis

The diagnosis of sarcoidosis in a patient living with HIV infection is an uncommon event and a challenge for clinicians. Clinical manifestations are variable and fluctuating depending to adherence to ARV therapy and to the level of CD4 count. We analyze here one chronic case in which sarcoidosis appeared clinically two years after pulmonary tuberculosis. The course of the disease was influenced and prolonged by frequent interruptions of antiretroviral therapy. Moreover the diagnosis and the decision to treat have been delayed by the need of exclusion of other pathologies, principally tuberculosis reactivation/reinfection, other mycobacterial diseases, hematologic malignancies. We propose a simplified flowchart for diagnosis and follow up of sarcoidosis, which may also be applied to patients with HIV infection. Diagnosis of latent tuberculosis infection (LTBI) may be difficult in these patients, because the immunological paradox of sarcoidosis. For this reason, following exclusion of active tuberculosis, we advise to submit all sarcoidosis patients to IPT (isoniazid preventive therapy), when immunosuppressive therapy is started

JCV-specific T-cells producing IFN-gamma are differently associated with PmL occurrence in HIV patients and liver transplant recipients

Aim of this work was to investigate a possible correlation between the frequency of JCV-specific T-cells and PML occurrence in HIV-infected subjects and in liver transplant recipients. A significant decrease of JCV-specific T-cells was observed in HIV-PML subjects, highlighting a close relation between JCV-specific T-cell immune impairment and PML occurrence in HIV-subjects. Interestingly, liver-transplant recipients (LTR) showed a low frequency of JCV-specific T-cells, similar to HIV-PML subjects. Nevertheless, none of the enrolled LTR developed PML, suggesting the existence of different immunological mechanisms involved in the maintenance of a protective immune response in LT

Exploring the G-quadruplex binding and unwinding activity of the bacterial FeS helicase DinG

Despite numerous reports on the interactions of G-quadruplexes (G4s) with helicases, systematic analysis addressing the selectivity and specificity of each helicase towards a variety of G4 topologies are scarce. Among the helicases able to unwind G4s are those containing an iron-sulphur (FeS) cluster, including both the bacterial DinG (found in E. coli and several pathogenic bacteria) and the medically important eukaryotic homologues (XPD, FancJ, DDX11 and RTEL1). We carried out a detailed study of the interactions between the E. coli DinG and a variety of G4s, by employing physicochemical and biochemical methodologies. A series of G4-rich sequences from different genomic locations (promoter and telomeric regions), able to form unimolecular G4 structures with diverse topologies, were analyzed (c-KIT1, KRAS, c-MYC, BCL2, Tel23, T30695, Zic1). DinG binds to most of the investigated G4s with little discrimination, while it exhibits a clear degree of unwinding specificity towards different G4 topologies. Whereas previous reports suggested that DinG was active only on bimolecular G4s, here we show that it is also able to bind to and resolve the more physiologically relevant unimolecular G4s. In addition, when the G4 structures were stabilized by ligands (Pyridostatin, PhenDC3, BRACO-19 or Netropsin), the DinG unwinding activity decreased and in most cases was abolished, with a pattern that is not simply explained by a change in binding affinity. Overall, these results have important implications for the biochemistry of helicases, strongly suggesting that when analysing the G4 unwinding property of an enzyme, it is necessary to investigate a variety of G4 substrates

How Can Scientific Literature Support Decision-Making in the Renovation of Historic Buildings? An Evidence-Based Approach for Improving the Performance of Walls

Buildings of heritage significance due to their historical, architectural, or cultural value, here called historic buildings, constitute a large proportion of the building stock in many countries around the world. Improving the performance of such buildings is necessary to lower the carbon emissions of the stock, which generates around 40% of the overall emissions worldwide. In historic buildings, it is estimated that heat loss through external walls contributes significantly to the overall energy consumption, and is associated with poor thermal comfort and indoor air quality. Measures to improve the performance of walls of historic buildings require a balance between energy performance, indoor environmental quality, heritage significance, and technical compatibility. Appropriate wall measures are available, but the correct selection and implementation require an integrated process throughout assessment (planning), design, construction, and use. Despite the available knowledge, decision-makers often have limited access to robust information on tested retrofit measures, hindering the implementation of deep renovation. This paper provides an evidence-based approach on the steps required during assessment, design, and construction, and after retrofitting through a literature review. Moreover, it provides a review of possible measures for wall retrofit within the deep renovation of historic buildings, including their advantages and disadvantages and the required considerations based on context

Análisis del potencial de ahorro mediante la aplicación de medidas de rehabilitación energética

CIES2020 - XVII Congresso Ibérico e XIII Congresso Ibero-americano de Energia SolarRESUMEN: En este artículo se presentan dos nuevas herramientas web que permiten cuantificar el potencial de rehabilitación en edificios residenciales del Principado de Asturias. La mejora energética se ha calculado mediante una metodología de simulación que identifica los casos más representativos, analiza su comportamiento energético través del acoplamiento entre TRNSYS y GenOpt, y realiza un post-procesado para calcular los potenciales finales. Se han identificados dos categorías de viviendas: unifamiliares y bloques de cuatro, siete y diez plantas; dos configuraciones para las condiciones de contorno: aisladas y adosadas; cuatro normativas edificatorias y varios porcentajes de sombra en las ventanas. Los mayores potenciales de rehabilitación se obtienen para las viviendas unifamiliares más antiguas, disminuyendo a medida que aumentan los requisitos normativos. Los bloques de viviendas presentan similares patrones pero con porcentajes inferiores. Finalmente, las configuraciones aisladas alcanzan mayores potenciales frente a las adosadas.ABSTRACT: This article presents two new web tools that allow quantifying the refurbishment potential in residential buildings in the Principado de Asturias. The energy savings have been calculated using a simulation methodology that identifies the most representative cases, analyzes their energy performance through the coupling between TRNSYS and GenOpt, and performs post-processing analyses to calculate the final potentials. Two categories of buildings have been identified: single-family and blocks of four, seven and ten floors; two configurations for boundary conditions: isolated and semi-detached or linear; four building regulations and various percentages of shade in windows. The greatest refurbishment potentials are obtained for older single-family dwellings, decreasing as regulatory requirements increase. Similar patterns are reached by blocks but with lower percentages. Finally, isolated configurations achieve higher potentials compared to semi-detached or linear configurations.info:eu-repo/semantics/publishedVersio

Conservation-compatible retrofit solutions in historic buildings: An integrated approach

Historic, listed, or unlisted, buildings account for 30% of the European building stock. Since they are complex systems of cultural, architectural, and identity value, they need particular attention to ensure that they are preserved, used, and managed over time in a sustainable way. This implies a demand for retrofit solutions able to improve indoor thermal conditions while reducing the use of energy sources and preserving the heritage significance. Often, however, the choice and implementation of retrofit solutions in historic buildings is limited by socio-technical barriers (regulations, lack of knowledge on the hygrothermal behaviour of built heritage, economic viability, etc.). This paper presents the approach devised in the IEA-SHC Task 59 project (Renovating Historic Buildings Towards Zero Energy) to support decision makers in selecting retrofit solutions, in accordance with the provision of the EN 16883:2017 standard. In particular, the method followed by the project partners to gather and assess compatible solutions for historic buildings retrofitting is presented. It focuses on best practices for walls, windows, HVAC systems, and solar technologies. This work demonstrates that well-balanced retrofit solutions can exist and can be evaluated case-by-case through detailed assessment criteria. As a main result, the paper encourages decision makers to opt for tailored energy retrofit to solve the conflict between conservation and energy performance requirements

Which executive functioning deficits are associated with AD/HD, ODD/CD and comorbid AD/HD+ODD/CD?

Item does not contain fulltextThis study investigated (1) whether attention deficit/hyperactivity disorder (AD/HD) is associated with executive functioning (EF) deficits while controlling for oppositional defiant disorder/conduct disorder (ODD/CD), (2) whether ODD/CD is associated with EF deficits while controlling for AD/HD, and (3)~whether a combination of AD/HD and ODD/CD is associated with EF deficits (and the possibility that there is no association between EF deficits and AD/HD or ODD/CD in isolation). Subjects were 99~children ages 6–12 years. Three putative domains of EF were investigated using well-validated tests: verbal fluency, working memory, and planning. Independent of ODD/CD, AD/HD was associated with deficits in planning and working memory, but not in verbal fluency. Only teacher rated AD/HD, but not parent rated AD/HD, significantly contributed to the prediction of EF task performance. No EF deficits were associated with ODD/CD. The presence of comorbid AD/HD accounts for the EF deficits in children with comorbid AD/HD+ODD/CD. These results suggest that EF deficits are unique to AD/HD and support the model proposed by R. A. Barkley (1997).17 p

An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019

Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism

INPP4B overexpression and c-KIT downregulation in human achalasia.

BACKGROUND: Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. METHODS: Esophageal full-thickness biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the "edgeR" option of R-Bioconductor. Data were validated by real-time RT-PCR, western blotting and immunohistochemistry. KEY RESULTS: Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P 64 10-3 . Nine genes with a P 64 10-4 were further validated. CYR61, CTGF, c-KIT, DUSP5, EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP4B, whereas c-KIT immunolabeling resulted downregulated. As INPP4B regulates Akt pathway, we used western blot to show that phospho-Akt was significantly reduced in achalasia patients vs controls. CONCLUSIONS & INFERENCES: The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia