Single-cell profiling reveals distinct immune response landscapes in tuberculous pleural effusion and non-TPE

BackgroundTuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and remains a major health threat worldwide. However, a detailed understanding of the immune cells and inflammatory mediators in Mtb-infected tissues is still lacking. Tuberculous pleural effusion (TPE), which is characterized by an influx of immune cells to the pleural space, is thus a suitable platform for dissecting complex tissue responses to Mtb infection.MethodsWe employed singe-cell RNA sequencing to 10 pleural fluid (PF) samples from 6 patients with TPE and 4 non-TPEs including 2 samples from patients with TSPE (transudative pleural effusion) and 2 samples with MPE (malignant pleural effusion).ResultCompared to TSPE and MPE, TPE displayed obvious difference in the abundance of major cell types (e.g., NK, CD4+T, Macrophages), which showed notable associations with disease type. Further analyses revealed that the CD4 lymphocyte population in TPE favored a Th1 and Th17 response. Tumor necrosis factors (TNF)-, and XIAP related factor 1 (XAF1)-pathways induced T cell apoptosis in patients with TPE. Immune exhaustion in NK cells was an important feature in TPE. Myeloid cells in TPE displayed stronger functional capacity for phagocytosis, antigen presentation and IFN-γ response, than TSPE and MPE. Systemic elevation of inflammatory response genes and pro-inflammatory cytokines were mainly driven by macrophages in patients with TPE.ConclusionWe provide a tissue immune landscape of PF immune cells, and revealed a distinct local immune response in TPE and non-TPE (TSPE and MPE). These findings will improve our understanding of local TB immunopathogenesis and provide potential targets for TB therapy

Tregs: Where We Are and What Comes Next?

Regulatory T cells are usually recognized as a specialized subset of CD4+ T cells functioning in establishment and maintenance of immune tolerance. Meanwhile, there is emerging evidence that regulatory T cells (Tregs) are also present in various non-lymphoid tissues, and that they have unique phenotypes credited with activities distinct from regulatory function. Their development and function have been described in plenty of manuscripts in the past two decades. However, with the deepening of research in recent years, emerging evidence revealed some novel mechanisms about how Tregs exert their activities. First, we discuss the expanding family of regulatory lymphocytes briefly and then, try to interpret how fork-head box P3 (Foxp3), a master regulator of the regulatory pathway in the development and function of regulatory T cells, functions. Subsequently, another part of our focus is varieties of tissue Tregs. Next, we primarily discuss recent research on how Tregs work and their faceted functions in terms of soluble mediators, functional proteins, and inhibitory receptors. In particular, unless otherwise noted, the term “Treg” is used here to refer specially to the “CD4+CD25+Foxp3+” regulatory cells

Radiation Exposure to Staff in Intensive Care Unit with Portable CT Scanner

Background. Bedside radiological procedures pose a risk of radiation exposure to ICU staff. The perception of risk may increase the degree of caution among the health care staff and raise new barriers preventing patients from obtaining prompt care. Objective. The aim of this study was to estimate the annual cumulative radiation dose to individual ICU staff. Methods. In this prospective study, forty subjects were required to wear thermoluminescent dosimeter badges during their working hours. The badges were analyzed to determine the exposure after 3 months. Results. A total of 802 radiological procedures were completed at bedside during the study period. The estimated annual dosage to doctors and nurses on average was 0.99 mSv and 0.88 mSv (p<0.001), respectively. Residents were subjected to the highest radiation exposure (1.04 mSv per year, p=0.002). The radiation dose was correlated with day shift working hours (r=0.426; p=0.006) and length of service (r=-0.403; p<0.01). Conclusions. With standard precautions, bedside radiological procedures—including portable CT scans—do not expose ICU staff to high dose of ionizing radiation. The level of radiation exposure is related to the daytime working hours and length of service

Relationship Between Short-Term Blood Pressure Variability and Incidence of Acute Kidney Injury in Critically Ill Patients

Background/Aims: Blood pressure (BP) variability is associated with cardiovascular events, and cerebral and renal damage. The aim of this study was to investigate any potential relationship between short-term BP variability and incidence of acute onset conditions, such as acute kidney injury (AKI), in critically ill patients. Methods: BP was monitored to analyze its variability in critically ill patients in present study. Short-term BP variability was assessed as average real variability (ARV), standard deviation (SD) and coefficient of variation (CV) of 24-hour BP. Results: A total of 565 patients were included, 41.2% (n=233) of which presented with AKI after admission (AKI stage I, n = 94; stage II, n = 37; stage III, n = 102). The mean APACHE II score was 21.5 for all patients. ARV of 24 h systolic BP was significantly higher in patients with AKI (p&#x3c;0.001). This association remained (p=0.006) after adjustment for potential confounders. The incidence of AKI increased with the ARV from 14.0% (ARV ≤6 mmHg) to 73.9% (ARV &#x3e;14 mmHg). A weak association was also found between BP variability and hospital mortality in critically ill patients. Conclusion: BP variability is correlated with the incidence of AKI in critically ill patients

Anatomic distribution of nerves and microvascular density in the human anterior vaginal wall: prospective study.

BACKGROUND: The presence of the G-spot (an assumed erotic sensitive area in the anterior wall of the vagina) remains controversial. We explored the histomorphological basis of the G-spot. METHODS: Biopsies were drawn from a 12 o'clock direction in the distal- and proximal-third areas of the anterior vagina of 32 Chinese subjects. The total number of protein gene product 9.5-immunoreactive nerves and smooth muscle actin-immunoreactive blood vessels in each specimen was quantified using the avidin-biotin-peroxidase assay. RESULTS: Vaginal innervation was observed in the lamina propria and muscle layer of the anterior vaginal wall. The distal-third of the anterior vaginal wall had significantly richer small-nerve-fiber innervation in the lamina propria than the proximal-third (p = 0.000) and in the vaginal muscle layer (p = 0.006). There were abundant microvessels in the lamina propria and muscle layer, but no small vessels in the lamina propria and few in the muscle layer. Significant differences were noted in the number of microvessels when comparing the distal- with proximal-third parts in the lamina propria (p = 0.046) and muscle layer (p = 0.002). CONCLUSIONS: Significantly increased density of nerves and microvessels in the distal-third of the anterior vaginal wall could be the histomorphological basis of the G-spot. Distal anterior vaginal repair could disrupt the normal anatomy, neurovascular supply and function of the G-spot, and cause sexual dysfunction

Rapid and Simple Detection of Trichosporon asahii by Optimized Colony PCR

Trichosporon asahii is the major pathogen causing invasive trichosporonosis. Conventional methods of its detection are time-consuming or costly and often require complex DNA extraction and purification steps, which hinders rapid clinical diagnosis. In this study, we evaluated colony PCR, which directly uses colonies or trace clinical samples as the template for amplification, for rapid detection of T. asahii infection. Four methods, namely, direct colony, freeze-thaw, glass beads, and enzymolysis, were compared to select the best DNA extraction strategy. We subsequently designed and screened species-specific primers targeting the intergenic spacer 1 (IGS1) of the ribosomal DNA of T. asahii and used them to detect mock infection clinical samples. The species-specific colony PCR based on glass beads proved advantageous, with short procedure time (154.8 ± 0.6 min), good sensitivity (detection limit, 102 CFU/mL), and specificity for T. asahii, indicating that this method can be used for the rapid and simple identification of clinical samples of T. asahii infection

Comparison of the LA and BI model on all combinations against biofilm cell of <i>T</i>. <i>asahii</i> CBS2479.

<p>Comparison of the LA and BI model on all combinations against biofilm cell of <i>T</i>. <i>asahii</i> CBS2479.</p