The elevated systemic cytokine levels in HIV patients are not associated with an elevated pulmonary cytokine environment.

Background HIV-positive patients on anti-retroviral therapy (ART) are at higher risk of developing many non-AIDS related chronic diseases, including chronic obstructive pulmonary disease (COPD), compared to HIV-negative individuals. While the mechanisms are not clear, a persistent pro-inflammatory state appears to be a key contributing factor. The aims of this study were to investigate whether HIV-positive patients without COPD present evidence of potentially predisposing abnormal pulmonary cytokine/chemokine environment and to explore the relationship between pulmonary and systemic cytokine levels. Methods This study included 39 HIV-seropositive and 34 HIV-seronegative subjects without COPD. All were subjected to outpatient bronchoscopy with bronchoalveolar lavage fluid (BALF) aspiration and blood sample collection. The levels of 21 cytokines and chemokines were measured in plasma and BALF using a bead-based multi-analyte assay. Results In plasma, HIV-infected patients showed significantly increased circulating levels of pro-inflammatory (TNFα) and Th1-associated cytokines (IL-12p70) as well as several chemokines (CXCL11 and CX3CL1). However, no statistically significant differences were found in the numbers of cells, the concentrations of protein and urea as well as cytokine levels in the BALFs of HIV-positive patients when compared to controls. Correlation analysis indicated a potential modulatory effect of the BMI in HIV-seropositive individuals. Conclusions While our results are consistent with the existence of a systemic pro-inflammatory state in HIV-infected patients, they did not detect significant differences in cytokine levels and other inflammatory markers in the lungs of HIV-positive individuals when compared to HIV-negative controls

Age-associated gut dysbiosis, marked by loss of butyrogenic potential, correlates with altered plasma tryptophan metabolites in older people living with HIV.

Background: Imbalance in tryptophan (TRP) metabolism and its neuroactive metabolites, serotonin and kynurenine (KYN), is a known pathogenic mechanism underlying neurocognitive impairment. Gut microbiota plays an important role in TRP metabolism, and the production of these neuroactive molecules affects neurocognitive function. Although both HIV infection and normal aging independently induce gut dysbiosis and influence TRP metabolism, their interactive effects on compositional/functional changes in gut microbiota and consequent alterations in TRP metabolites remain largely undetermined. Methods: Older people living with HIV infection (PLWH, aged 50–70 years, n = 22) were enrolled in this cross-sectional pilot study. Metagenomic analysis of fecal microbiome using 16S Ribosomal ribonucleic acid gene sequencing and metabolomics analysis of plasma using mass spectrometry with a reverse-phase iquid chromatography tandem mass spectrometry were performed. Statistical analyses included the univariate linear regression and Spearman correlation analyses. Results: Age-associated changes in plasma levels of key neuroactive TRP metabolites, serotonin and KYN, were seen in PLWH. Specifically, we observed age-dependent decreases in serotonin and increases in KYN and KYN-to-TRP ratio, indicative of dysfunctional TRP metabolism. Furthermore, the gut dysbiosis seen in older PLWH is characterized by a reduction of Firmicutes/Bacteroidetes ratio and butyrate-producing microbial families Lachnospiraceae and Lactobacillaceae. Of importance, correspondent with gut dysbiosis, increasing age was significantly associated with decreased plasma butyrate levels, which in turn correlated positively with serotonin and negatively with KYN/TRP ratio. Conclusions: Age-dependent gut microbial dysbiosis distinguished by a decrease in butyrogenic potential is a key pathogenic feature associated with the shift in TRP metabolism from serotonin to KYN in older PLWH

Extracting Social Support and Social Isolation Information from Clinical Psychiatry Notes: Comparing a Rule-based NLP System and a Large Language Model

Background: Social support (SS) and social isolation (SI) are social determinants of health (SDOH) associated with psychiatric outcomes. In electronic health records (EHRs), individual-level SS/SI is typically documented as narrative clinical notes rather than structured coded data. Natural language processing (NLP) algorithms can automate the otherwise labor-intensive process of data extraction. Data and Methods: Psychiatric encounter notes from Mount Sinai Health System (MSHS, n=300) and Weill Cornell Medicine (WCM, n=225) were annotated and established a gold standard corpus. A rule-based system (RBS) involving lexicons and a large language model (LLM) using FLAN-T5-XL were developed to identify mentions of SS and SI and their subcategories (e.g., social network, instrumental support, and loneliness). Results: For extracting SS/SI, the RBS obtained higher macro-averaged f-scores than the LLM at both MSHS (0.89 vs. 0.65) and WCM (0.85 vs. 0.82). For extracting subcategories, the RBS also outperformed the LLM at both MSHS (0.90 vs. 0.62) and WCM (0.82 vs. 0.81). Discussion and Conclusion: Unexpectedly, the RBS outperformed the LLMs across all metrics. Intensive review demonstrates that this finding is due to the divergent approach taken by the RBS and LLM. The RBS were designed and refined to follow the same specific rules as the gold standard annotations. Conversely, the LLM were more inclusive with categorization and conformed to common English-language understanding. Both approaches offer advantages and are made available open-source for future testing.Comment: 2 figures, 3 table

Quality and performance evaluation of TPU based Fused Deposition Modeling : Investigations on dimenison, surface topography and mechanical properties.

Fused Deposition Modeling (FDM) is a complex process that exhibits muchdifficulty in determining optimal parameters due to the presence of a large numberof conflicting parameters that will influence the part quality and materialproperties. The technology has the capability to fulfill the industrial requirementby customization of consumer-based product. Hence, it is of utmost importance toproduce the part with the best possible quality which can be achieved throughoptimal selection of process parameters.In this project, investigations on the quality of 3D printed Thermoplasticpolyurethane (TPU) samples by FDM process with different print settings areperformed. The quality and performance tests includes dimensional accuracy,surface topography and mechanical properties with different test artefacts.Dimensions of the printed sample are compared with the CAD model to determinethe accuracy of the print. Further the samples are post processed by plastic mediablasting and comparisons are drawn between the surface topography of as-printedand post-processed study samples. Tests are conducted on Tear strength, Tensilestrength, fogging and flammability to determine the mechanical properties of 3Dprinted TPU samples.The results suggest that the variation in dimensions is higher in Z direction or inthe direction of the stacking layers. The surface analysis suggests higher surfaceroughness on as-printed samples compared to post-processed samples. Postprocessing is found to have induced matte finish on the test samples. The tests onthe mechanical properties suggest good tensile and tear resistance

Impact of catheter fragmentation followed by local intrapulmonary thrombolysis in acute high risk pulmonary embolism as primary therapy

Background: Pulmonary embolism (PE) with more than 50% compromise of pulmonary circulation results significant right ventricular (RV) afterload leading to progressive RV failure, systemic hypotension and shock. Prompt restoration of thrombolysis, surgical embolectomy, or percutaneous mechanical thrombectomy (PMT) prevents progressive hemodynamic decline. We report our single center experience in high risk PE patients treated with standard pigtail catheter mechanical fragmentation followed by intrapulmonary thrombolysis as a primary therapy. Methods: 50 consecutive patients with diagnosis of high risk PE defined as having shock index >1 with angiographic evidence of >50% pulmonary arterial occlusion are included in the present study. All patients underwent emergent cardiac catheterization. After ensuring flow across pulmonary artery with mechanical breakdown of embolus by rotating 5F pigtail catheter; bolus dose of urokinase (4400 IU/kg) followed by infusion for 24 h was given in the thrombus. Hemodynamic parameters were recorded and follow up pulmonary angiogram was done. Clinical and echo follow up was done for one year. Results: Pigtail rotational mechanical thrombectomy restored antegrade flow in all patients. The mean pulmonary artery pressure, Miller score, Shock index decreased significantly from 41 ± 8 mmHg, 20 ± 5, 1.32 ± 0.3 to 24.52 ± 6.89, 5.35 ± 2.16, 0.79 ± 0.21 respectively (p < 0.0001). In-hospital major complications were seen in 4 patients. There was a statistically significant reduction of PA pressures from 62 ± 11 mmHg to 23±6 mmHg on follow up. Conclusions: Rapid reperfusion of pulmonary arteries with mechanical fragmentation by pigtail catheter followed by intrapulmonary thrombolysis results in excellent immediate and intermediate term outcomes in patients presenting with high risk pulmonary embolism