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BackgroundSeveral studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD3+, CD4+ and CD8+) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea.MethodsSurgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD68 for macrophages, anti-elastase for neutrophils, and anti-CD3, anti-CD4, anti-CD8 for CD3+TLs, CD4+TLs, and CD8+TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV1, FVC, TLC, DLCO, PaO2, PaCO2 and P(A-a)O2)] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale.ResultsElastase positive cells accounted for the 7.04% ± 1.1 of total cells, CD68+ cells for the 16.6% ± 2, CD3+ TLs for the 28.8% ± 7, CD4+ TLs for the 14.5 ± 4 and CD8+ TLs for the 13.8 ± 4. CD8+TLs correlated inversely with FVC % predicted (rs = -0.67, p = 0.01), TLC % predicted (rs = -0.68, p = 0.01), DLCO % predicted (rs = -0.61, p = 0.04), and PaO2 (rs = -0.60, p = 0.04). Positive correlations were found between CD8+TLs and P(A-a)O2 (rs = 0.65, p = 0.02) and CD8+TLs and MRC score (rs = 0.63, p = 0.02). Additionally, CD68+ cells presented negative correlations with both FVC % predicted (rs = -0.80, p = 0.002) and FEV1 % predicted (rs = -0.68, p = 0.01).ConclusionIn UIP/IPF tissue infiltrating mononuclear cells and especially CD8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.

Technical debt (TD) describes quality compromises that can yield short-term benefits but may negatively affect the quality of software products in the long run. A wide range of tools and techniques have been introduced over the years in order for the developers to be able to determine and manage TD. However, being able to also predict its future evolution is of equal importance to avoid its accumulation, and, in turn, the unlikely event of making the project unmaintainable. Although recent research endeavors have showcased the feasibility of building accurate project-specific TD forecasting models, there is a gap in the field regarding cross-project TD forecasting. Cross-project TD forecasting is of practical importance, since it would enable the application of pre-existing forecasting models on previously unknown software projects, especially new projects that do not exhibit sufficient commit history to enable the construction of project-specific models. To this end, in the present paper, we focus on cross-project TD forecasting, and we examine whether the consideration of similarities between software projects could be the key for more accurate forecasting. More specifically, we propose an approach based on data clustering. In fact, a relatively large repository of software projects is divided into clusters of similar projects with respect to their TD aspects, and specific TD forecasting models are built for each cluster, using regression algorithms. According to our approach, previously unknown software projects are assigned to one of the defined clusters and the cluster-specific TD forecasting model is applied to predict future TD values. The approach was evaluated through several experiments based on real-world applications. The results of the analysis suggest that the proposed approach comprises a promising solution for accurate cross-project TD forecasting.

BackgroundSingle-incision laparoscopic surgery (SILS) is a new technique that aims to minimize abdominal wall trauma and improve cosmesis. Concerns have been raised about the risk of trocar-site hernia following SILS. This study aims to assess the risk of trocar-site hernia following SILS compared to conventional laparoscopic surgery, and investigate whether current evidence is conclusive.MethodsWe performed a systematic search of MEDLINE, AMED, CINAHL, CENTRAL, and OpenGrey. We considered randomized clinical trials comparing the risk of trocar-site hernia with SILS and conventional laparoscopic surgery. Pooled odds ratios with 95% confidence intervals (CI) were calculated using the Mantel–Haenszel method. Trial sequential analysis using the Land and DeMets method was performed to assess the possibility of type I error and compute the information size.ResultsTwenty-three articles reporting a total of 2471 patients were included. SILS was associated with higher odds of trocar-site hernia compared to conventional laparoscopic surgery (odds ratio 2.37, 95% CI 1.25–4.50, p = 0.008). There was no evidence of between-study heterogeneity or small-study effects. The information size was calculated at 1687 patients and the Z-curve crossed the O’Brien–Fleming α-spending boundaries at 1137 patients, suggesting that the evidence of higher risk of trocar-site hernia with SILS compared to conventional laparoscopic surgery can be considered conclusive.ConclusionsSingle-incision laparoscopic procedures through the umbilicus are associated with a higher risk of trocar-site hernia compared to conventional laparoscopic surgery.

Background Alterations in kidney-associated adipose tissue depots, specifically renal sinus (RSAT) and perirenal adipose tissue (PRAT), may contribute to metabolic, cardiovascular, and chronic kidney diseases. We compared transcriptomic profiles and phenotypes, including adipocyte size, glucose uptake, and insulin action in RSAT and PRAT from healthy individuals. Methods Subcutaneous (SAT), omental (OAT) and renal adipose tissue biopsies were collected from healthy kidney donors (20 women, 20 men; BMI 20 to 36 kg/m 2 ). Adipocyte size and basal and insulin-stimulated glucose uptake rate were measured in isolated adipocytes. Transcriptomic profiling and immune cell composition estimates (RNA seq, n  = 30), were performed to evaluate differences between PRAT and RSAT, with OAT as a benchmark. Results PRAT exhibited significantly larger adipocytes and higher insulin-stimulated glucose uptake than RSAT. Of 1113 significantly differentially expressed genes (DEGs) (PRAT: 571 down- and 542 upregulated), thermogenic and metabolic genes ( UCP1 , CIDEA , and CKMT1B ) were enriched in PRAT, while inflammation-related genes ( NFKBIA , BIRC3 , and IRF1 ) in RSAT. Pathway analysis indicated activation of metabolic pathways (TCA cycle and oxidative phosphorylation), in PRAT, which contrasts with the immune and inflammatory pathways in RSAT and OAT. Immune cell gene signatures revealed an anti-inflammatory environment in PRAT (eosinophils and activated NK cells), and a pro-inflammatory profile in RSAT (M0 macrophages). Immunohistochemistry confirmed higher CD68- and IL1B-positive cells in RSAT than in PRAT. When overweight individuals were compared to lean, genes related to the VEGF signaling were upregulated in PRAT and Ras signaling in RSAT. Additionally, metabolic pathways linked to the TCA cycle as well as carbon and fatty acid metabolism were downregulated. Conclusions The different kidney-associated adipose tissue depots exhibit distinct gene expression and functional profiles. PRAT displays higher expression of thermogenic markers and less inflammatory profile compared to RSAT and also OAT. In contrast, RSAT exhibits an inflammatory and macrophage-enriched profile, more closely resembling OAT. This study highlights the heterogeneity of the kidney-associated adipose tissue depots and could suggest that an excessive amount of RSAT may impact development of metabolic, cardiovascular, and chronic kidney diseases.

The global prevalence of Type 2 Diabetes (T2D) poses significant public health challenges due to its associated severe complications. Insulin resistance is central to T2D pathophysiology, particularly affecting adipose tissue function. This cross-sectional observational study investigates metabolic alterations in subcutaneous adipose tissue (SAT) associated with T2D to identify potential therapeutic targets. We conducted a comprehensive metabolomic analysis of SAT from 40 participants (20 T2D, 20 ND-T2D), matched for sex, age, and BMI (Body Mass Index). Metabolite quantification was performed using GC/MS and LC/MS/MS platforms. Correlation analyses were conducted to explore associations between metabolites and clinical parameters. We identified 378 metabolites, including significant elevations in TCA cycle (tricarboxylic acid cycle) intermediates, branched-chain amino acids (BCAAs), and carbohydrates, and a significant reduction in the nucleotide-related metabolites in T2D subjects compared to those without T2D. Obesity exacerbated these alterations, particularly in amino acid metabolism. Adipocyte size negatively correlated with BCAAs, while adipocyte glucose uptake positively correlated with unsaturated fatty acids and glycerophospholipids. Our findings reveal distinct metabolic dysregulation in adipose tissue in T2D, particularly in energy metabolism, suggesting potential therapeutic targets for improving insulin sensitivity and metabolic health. Future studies should validate these findings in larger cohorts and explore underlying mechanisms to develop targeted interventions.

Infective endocarditis (IE) due to species is a rare disease representing about 1-2% of all IE cases and carries a high mortality rate. Given the rarity of the disease, there are no clear guidelines on the type and duration of antifungal therapy. Thus, long-term or even life-long antifungal treatment is commonly used. We report two patients with prosthetic valve IE and persistent candidemia that failed conservative treatment and ultimately developed heart failure. They underwent prosthetic valve replacement and prolonged antifungal treatment with favorable outcome. IE commonly occurs in the setting of underlying malignancy, chronic liver disease, previous endocarditis, previous antimicrobial exposure, previous abdominal surgery, intravenous drug use, presence of a central venous catheter, and previous cardiac surgery. Both present patients had undergone a cardiac surgery and had a prosthetic heart valve, while one patient had an underlying autoimmune disease that could be associated with higher risk of IE. In both patients transthoracic ultrasound failed to diagnose IE. In our patients, conservative treatment alone was not enough to control the infection, thus, both patients underwent valve replacement and were subsequently treated with antifungals for 6 weeks. Furthermore, both patients were put on long-term antifungal suppression treatment. Given the absence of controlled randomized trials, the treatment of endocarditis mostly relies on experts' opinion, and, thus, future studies focusing on the type and duration of antifungal treatment are required.

Health care workers (HCWs) face a higher risk of infection, since they work at the front line of COVID-19 patients’ management. Misinterpretations of current scientific evidence among HCWs may impact the delivery of appropriate care to COVID-19 patients and increase the risk of SARS-CoV-2 transmission in the hospital setting. Moreover, knowledge may affect HCWs perceptions depending on their broad beliefs and past experiences. The aim of this study was to explore the knowledge and perceptions of HCWs regarding COVID-19 issues during the second wave of the pandemic. A cross-sectional survey, involving a printed questionnaire, was conducted from 21 October 2020 to 31 January 2021 in four tertiary care hospitals located at four distant geographical regions in Greece. In total, 294 HCWs participated in this study. The majority of HCWs provided precise responses regarding general knowledge, perceptions, and practices concerning the COVID-19 pandemic. However, responses on hand hygiene and antimicrobial use in HCWs with COVID-19 were mistaken. This study reveals a certain degree of misconceptions and knowledge gaps in HCWs everyday practice, especially regarding hand hygiene and antimicrobial use in COVID-19 patients.

Health care workers (HCWs) face a higher risk of infection, since they work at the front line of COVID-19 patients' management. Misinterpretations of current scientific evidence among HCWs may impact the delivery of appropriate care to COVID-19 patients and increase the risk of SARSCoV- 2 transmission in the hospital setting. Moreover, knowledge may affect HCWs perceptions depending on their broad beliefs and past experiences. The aim of this study was to explore the knowledge and perceptions of HCWs regarding COVID-19 issues during the second wave of the pandemic. A cross-sectional survey, involving a printed questionnaire, was conducted from 21 October 2020 to 31 January 2021 in four tertiary care hospitals located at four distant geographical regions in Greece. In total, 294 HCWs participated in this study. The majority of HCWs provided precise responses regarding general knowledge, perceptions, and practices concerning the COVID-19 pandemic. However, responses on hand hygiene and antimicrobial use in HCWs with COVID-19 were mistaken. This study reveals a certain degree of misconceptions and knowledge gaps in HCWs everyday practice, especially regarding hand hygiene and antimicrobial use in COVID-19 patients.