Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete ...cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics.
Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon ...nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we (47) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique (2). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m(3), 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5-20 microg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K-ras gene locus in the lung of C57BL/6 mice.
Nanoparticles have a fundamental dimension of <100 nm. However, on suspension in media, agglomerates of nanoparticles are the more common structure. This is particularly evident in prior ...intratracheal instillation or aspiration studies of single-walled carbon nanotubes (SWCNT), in which granulomatous lesions encased by epithelioid macrophages were produced by large agglomerates. In this study, we tested the hypothesis of whether exposure to more dispersed SWCNT structures would alter pulmonary distribution and response. A dispersed preparation of single-walled carbon nanotubes (DSWCNT) with a mean diameter of 0.69 microm was given by pharyngeal aspiration to C57BL/6 mice. Electron microscopy demonstrated a highly dispersed, interstitial distribution of DSWCNT deposits by 1 day postexposure. Deposits were generally <1 microm. Macrophage phagocytosis of DSWCNT was rarely observed at any time point. Lung responses were studied by lavage and morphometry at 1 h, 1 day, 7 day, and 1 mo after a single DSWCNT exposure of 10 microg/mouse. Lung sections and lavage cells demonstrated an early, transient neutrophilic and inflammatory phase that rapidly resolved and was similar to that observed with large agglomerates. No granulomatous lesions or epithelioid macrophages were detected. Morphometric measurement of Sirius red staining was used to assess the connective tissue response. The average thickness of connective tissue in alveolar regions was 0.10 +/- 0.02, 0.09 +/- 0.02, 0.10 +/- 0.01, 0.48 +/- 0.04, and 0.88 +/- 0.19 microm for PBS and 1-h, 1-day, 7-day, and 1-mo postexposure groups, respectively. The results demonstrate that dispersed SWCNT are rapidly incorporated into the alveolar interstitium and that they produce an increase in collagen deposition.
The GLIMPSE (Galactic Legacy Mid-Plane Survey Extraordinaire) Point Source Catalog of 630 million mid-infrared sources toward the inner Galaxy, 10 , "l" 65 , 65 and "b" , 1, was used to determine the ...distribution of stars in Galactic longitude, l, latitude, b, and apparent magnitude, m. The counts versus longitude can be approximated by the modified Bessel function N = N sub(0)(l/l sub(0)) K sub(1)(l/l sub(0)), where l sub(0) is insensitive to limiting magnitude, band choice, and side of Galactic center: l sub(0) = 17-30 with a best-fit value in the 4.5 km band of l sub(0) = 24 c 4. Modeling the source distribution as an exponential disk yields a radial scale length of H sub(*) = 3.9 c 0.6 kpc. There is a pronounced north-south asymmetry in source counts for "l" 30, with 625% more stars in the north. For l = 10-30, there is a strong enhancement of stars of m = 11.5-13.5 mag. A linear bar passing through the Galactic center with half-length R sub(bar) = 4.4 c 0.5 kpc, tilted by h = 44 c 10 to the Sun-Galactic center line, provides the simplest interpretation of these data. We examine the possibility that enhanced source counts at l = 26-28, 31.5-34, and 306-309 are related to Galactic spiral structure. Total source counts are depressed in regions where the counts of red objects (m sub(K)-m sub(8.0) > 3) peak. In these areas, the counts are reduced by extinction due to molecular gas, high diffuse backgrounds associated with star formation, or both.
We determine and tabulate A sub( lambda )/A sub(K), the wavelength dependence of interstellar extinction, in the Galactic plane for 1.25 mu m less than or equal to lambda less than or equal to mu 8.0 ...mu m along two lines of sight: l = 42 degree and 284 degree . The first is a relatively quiescent and unremarkable region; the second contains the giant H II region RCW 49, as well as a "field" region unrelated to the cluster and nebulosity. Areas near these Galactic longitudes were imaged at J, H, and K bands by 2MASS and at 3-8 mu m by Spitzer for the GLIMPSE Legacy program. We measure the mean values of the color excess ratios (A sub( lambda ) - A sub(K))/(A sub(J) - A sub(K)) directly from the color distributions of observed stars. The extinction ratio between two of the filters, e.g., A sub(J)/A sub(K), is required to calculate A sub( lambda )/A sub(K) from those measured ratios. We use the apparent JHK magnitudes of giant stars along our two sight lines and fit the reddening as a function of magnitude (distance) to determine A sub(J)kpc super(-1), A sub(K)kpc super(-1), and A sub(J)/A sub(K). Our values of A sub( lambda )/A sub(K) show a flattening across the 3-8 mu m wavelength range, roughly consistent with the extinction measurements derived by Lutz and coworkers for the sight line toward the Galactic center.
Appendicitis continues to be a common surgical emergency in children, but its diagnosis remains challenging. Use of diagnostic imaging to confirm appendicitis has gained popularity in some countries ...because it is associated with lower negative appendicectomy rates. This study reports our centre's experience of adopting routine ultrasound for the investigation of suspected appendicitis in children.
A single-centre retrospective cohort study was performed investigating all children aged 5-16 years admitted under surgeons with suspected appendicitis, in January-December 2019. Primary outcomes were the rate of ultrasound use, its accuracy in diagnosing/excluding appendicitis and negative appendicectomy rate. Other outcomes were treatment received, length of stay and complications.
The majority of the 193 children with suspected appendicitis underwent a diagnostic ultrasound (87.5%). Ultrasound was highly sensitive (0.90, 95% confidence interval (CI) 0.81-0.96) and specific (1.0, 95% CI 0.96-1.0) for appendicitis in this study. Negative appendicectomy rate was extremely low (1.4%). Laparoscopic appendicectomy was the preferred management (75/86), with one case started open and no conversions to open. A minority of cases of simple appendicitis (10/86) were treated primarily with antibiotics. Rates of complex appendicitis and postoperative complications were similar to other studies.
Ultrasound can be highly sensitive and specific for appendicitis. Its routine use to confirm appendicitis prior to surgery is associated with a low negative appendicectomy rate. This is a major change in practice for a general surgical unit in the United Kingdom.
Laparoscopic adhesiolysis is increasingly being used to treat adhesional small bowel obstruction (ASBO) as it has been associated with reduced postoperative length of stay (LOS) and faster recovery. ...However, concerns regarding limited working space, iatrogenic bowel injury and failure to relieve the obstruction have limited its uptake. This study reports our centre's experience of adopting laparoscopy as the standard operative approach.
A single-centre prospective cohort study was performed incorporating local data from the National Emergency Laparotomy Audit Database; January 2015 to December 2019. All patients undergoing surgery for ASBO were included. Patient demographic, operative and inhospital outcomes data were compared between different surgical approaches. Linear regression analysis was performed for LOS.
A total of 299 cases were identified. Overall, 76.3% of cases were started laparoscopically and 52.2% were completed successfully. Patients treated laparoscopically had lower Portsmouth - Physiological and Operative Severity Score for the enuMeration of Mortality and morbidity (P-POSSUM) predicted mortality (median 2.1 (interquartile range (IQR) 1.3-5.0) vs 5.7 (IQR 2.0-12.4),
=<0.001) and shorter postoperative LOS compared with open (median 4.2 days (IQR 2.5-8.2) vs 11.3 days (IQR 7.3-16.6),
=0.000). Inhospital mortality was lower in the laparoscopic group (2 vs 7 deaths,
=<0.001). In regression analysis, laparoscopic surgery was found to have the strongest association with postoperative LOS (β -8.51 (-13.87 to -3.16)
=0.002) compared with open surgery.
Laparoscopy is a safe and feasible approach for adhesiolysis in the majority of patients with ASBO. It is associated with reduced LOS with no impact on complications or mortality.
Objectives
To investigate the association between chemsex drug use and HIV clinic attendance among gay and bisexual men in London.
Methods
A cross‐sectional survey of adults (> 18 years) diagnosed ...with HIV for > 4 months, attending seven London HIV clinics (May 2014 to August 2015).
Participants self‐completed an anonymous questionnaire linked to clinical data. Sub‐optimal clinic attenders had missed one or more HIV clinic appointments in the past year, or had a history of non‐attendance for > 1 year.
Results
Over half (56%) of the 570 men who identified as gay or bisexual reported taking recreational drugs in the past 5 years and 71.5% of these men had used chemsex drugs in the past year. Among men reporting chemsex drug use (past year), 32.1% had injected any drugs in the past year. Sub‐optimal clinic attenders were more likely than regular attenders to report chemsex drug use (past year; 46.9% vs. 33.2%, P = 0.001), injecting any drugs (past year; 17.1% vs. 8.9%, P = 0.011) and recreational drug use (past 5 years; 65.5% vs. 48.8%, P < 0.001). One in five sub‐optimal attenders had missed an HIV clinic appointment because of taking recreational drugs (17.4% vs. 1.8%, P < 0.001). In multivariable logistic regression, chemsex drug use was significantly associated with sub‐optimal clinic attendance (adjusted odds ratio = 1.71, 95% confidence interval: 1.10–2.65, P = 0.02).
Conclusions
Our findings highlight the importance of systematic assessment of drug use and development of tools to aid routine assessment. We suggest that chemsex drug use should be addressed when developing interventions to improve engagement in HIV care among gay and bisexual men.
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