Emergency centre thoracotomy for penetrating trauma: Insights from 2 South African district-level emergency centres.

Introduction: Trauma is a major contributor to global disease burden, disproportionally affecting low- and middle-income countries, especially in the African Region. Emergency centre thoracotomy (ECT) is a potentially life-saving procedure for a sub-group of trauma patients in extremis. Most literature regarding ECT originated in high-income countries.

30-day outcomes in 1 000 consecutive laparoscopic cholecystectomies undertaken in four Cape metropole public hospitals.

Background: Laparoscopic cholecystectomy (LC) is the standard of care for symptomatic gallstone disease. The procedure has a steep learning curve and may result in significant postoperative morbidity and mortality. LC carries a morbidity of 1.

Outcomes of complex burn injury patients managed at two primary and one tertiary level burns facilities in the Western Cape province of South Africa - a retrospective review.

Background: This study aimed to compare factors contributing to a positive outcome of adult burn injury patients managed at two primary and one tertiary level Western Cape hospitals. These patients from the primary hospitals (PLHs) met the referral criteria for specialised care at the Tygerberg Hospital burns unit (TBU) but were not accepted or were accepted late.

Methods: A total of 1034 adult burn injury patients seen at two primary level ("A" and "B") hospitals and the TBU between 2016 and 2019 were retrospectively analysed.

Whether and how top management create flexibility in mental healthcare organizations: COVID-19 as a test case.

Purpose: Flexibility is essential for healthcare organizations to anticipate the increasing internal and external dynamics. Mental healthcare organizations in the Netherlands face major policy reforms made by the government, increasing involvement from municipalities and gradual replacement of clinical care with outpatient care. Top management plays an important strategic role in creating this flexibility because they make important choices, give direction and structure the organization.

Long-term outcome results after endovascular aortoiliac aneurysm repair with the bifurcated EXCLUDER Endoprosthesis.

Objective: To report the long-term outcome of patients presenting with an aortic, aortoiliac, or isolated common iliac aneurysm treated with the bifurcated EXCLUDER Endoprosthesis. Furthermore, potential differences in late outcome results between the original- and low-permeability endoprosthesis were analyzed.

Methods: A retrospective analysis of prospectively collected data of 182 patients who underwent endovascular aneurysm repair with the EXCLUDER Endoprosthesis between June 1998 and October 2015 in an academic, tertiary care center for aortic disease was performed.

The CD28-Transmembrane Domain Mediates Chimeric Antigen Receptor Heterodimerization With CD28.

Anti-CD19 chimeric antigen receptor (CD19-CAR)-engineered T cells are approved therapeutics for malignancies. The impact of the hinge domain (HD) and the transmembrane domain (TMD) between the extracellular antigen-targeting CARs and the intracellular signaling modalities of CARs has not been systemically studied. In this study, a series of 19-CARs differing only by their HD (CD8, CD28, or IgG) and TMD (CD8 or CD28) was generated.

Field survey of major infectious and reproductive diseases responsible for mortality and productivity losses of ruminants amongst Nigerian Fulani pastoralists.

Animal disease constitutes a major hurdle to improved livelihoods in rural Nigeria through the challenges of loss of productivity, livestock morbidity and mortality including reproductive losses. In order to design and implement impactful interventions, baseline data on the causes of such losses are needed. Therefore, the objective of the present study was to carry out targeted field surveys, including interviews with ruminant farmers, veterinary professionals and other stakeholders in livestock farming to establish the main causes of disease and mortality including abortions in cattle and small ruminants (SR).

Realistic evaluation of the Flexmonitor, a team program to maintain and reflect on flexibility.

Purpose: Flexibility is necessary in a dynamic healthcare environment. However, balancing flexibility and consistency is difficult for healthcare teams, especially when working in threatening conditions. Methods are needed to help teams create, monitor and maintain flexibility.

Does plastic waste kill mangroves? A field experiment to assess the impact of macro plastics on mangrove growth, stress response and survival.

The value of mangroves has been widely acknowledged, but mangrove forests continue to decline due to numerous anthropogenic stressors. The impact of plastic waste is however poorly known, even though the amount of plastic litter is the largest in the region where mangroves are declining the fastest: South East Asia. In this study, we examine the extent of the plastic waste problem in mangroves along the north coast of Java, Indonesia.

CRISPR screen in regulatory T cells reveals modulators of Foxp3.

Regulatory T (T) cells are required to control immune responses and maintain homeostasis, but are a significant barrier to antitumour immunity. Conversely, T instability, characterized by loss of the master transcription factor Foxp3 and acquisition of proinflammatory properties, can promote autoimmunity and/or facilitate more effective tumour immunity. A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective T therapies for autoimmune disease and cancer.

Multiple Environmental Signaling Pathways Control the Differentiation of RORγt-Expressing Regulatory T Cells.

RORγt-expressing Tregs form a specialized subset of intestinal CD4 Foxp3 cells which is essential to maintain gut homeostasis and tolerance to commensal microbiota. Recently, c-Maf emerged as a critical factor in the regulation of RORγt expression in Tregs. However, aside from c-Maf signaling, the signaling pathways involved in the differentiation of RORγt Tregs and their possible interplay with c-Maf in this process are largely unknown.

Thymically-derived Foxp3+ regulatory T cells are the primary regulators of type 1 diabetes in the non-obese diabetic mouse model.

Regulatory T cells (Tregs) are an immunosuppressive population that are identified based on the stable expression of the fate-determining transcription factor forkhead box P3 (Foxp3). Tregs can be divided into distinct subsets based on whether they developed in the thymus (tTregs) or in the periphery (pTregs). Whether there are unique functional roles that distinguish pTregs and tTregs remains largely unclear.

Co-creating a program for teams to maintain and reflect on their flexibility.

To prevent rigidity within teams in health care and to support teams in detecting early warning signs of decreasing flexibility, a program has been co-created in collaboration with mental healthcare teams. This program is intended to systematically monitor team behavior, and by doing so to facilitate team intervention. We aim to lay foundations for the further development of methods that can help teams to recognize and respond to processes going on under the surface.

Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes.

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by hyperglycemia due to progressive loss of pancreatic beta cells. Immune-mediated beta cell destruction drives the disease, but whether beta cells actively participate in the pathogenesis remains unclear. Here, we show that during the natural history of T1D in humans and the non-obese diabetic (NOD) mouse model, a subset of beta cells acquires a senescence-associated secretory phenotype (SASP).

A Mutation in the Transcription Factor Foxp3 Drives T Helper 2 Effector Function in Regulatory T Cells.

Regulatory T (Treg) cells maintain immune tolerance through the master transcription factor forkhead box P3 (FOXP3), which is crucial for Treg cell function and homeostasis. We identified an IPEX (immune dysregulation polyendocrinopathy enteropathy X-linked) syndrome patient with a FOXP3 mutation in the domain swap interface of the protein. Recapitulation of this Foxp3 variant in mice led to the development of an autoimmune syndrome consistent with an unrestrained T helper type 2 (Th2) immune response.

Author Correction: Discovery of stimulation-responsive immune enhancers with CRISPR activation.

In this Letter, analysis of steady-state regulatory T (Treg) cell percentages from Il2ra enhancer deletion (EDEL) and wild-type (WT) mice revealed no differences between them (Extended Data Fig. 9d). This analysis included two mice whose genotypes were incorrectly assigned.

Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity.

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis, but their presence in tumor tissues impairs anti-tumor immunity and portends poor prognoses in cancer patients. Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8 and CD4 effector T cells that eliminate tumors.

Discovery of stimulation-responsive immune enhancers with CRISPR activation.

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied.

Preliminary efficacy investigations of oral fipronil against Anopheles arabiensis when administered to Zebu cattle (Bos indicus) under field conditions.

Globally, malaria remains one of the most important vector-borne diseases despite the extensive use of vector control, including indoor residual spraying (IRS) and insecticide-treated nets (ITNs). These control methods target endophagic vectors, whereas some malaria vectors, such as Anopheles arabiensis, preferentially feed outdoors on cattle, making it a complicated vector to control using conventional strategies. Our study evaluated whether treating cattle with a capsule containing the active ingredient (AI) fipronil could reduce vector density and sporozoite rates, and alter blood feeding behavior, when applied in a small-scale field study.

Detection of Anaplasma spp. and Ehrlichia spp. anibodies, and Dirofilaria immitis antigens in dogs from seven locations of Morocco.

In Morocco no data has been published on canine exposure to Anaplasma spp., Borrrelia burgdorferi, and Ehrlichia spp., and only one report is available on the occurrence of Dirofilaria immitis in dogs.

Interleukin-33 and Interferon-γ Counter-Regulate Group 2 Innate Lymphoid Cell Activation during Immune Perturbation.

Group 2 innate lymphoid cells (ILC2s) and regulatory T (Treg) cells are systemically induced by helminth infection but also sustain metabolic homeostasis in adipose tissue and contribute to tissue repair during injury. Here we show that interleukin-33 (IL-33) mediates activation of ILC2s and Treg cells in resting adipose tissue, but also after helminth infection or treatment with IL-2. Unexpectedly, ILC2-intrinsic IL-33 activation was required for Treg cell accumulation in vivo and was independent of ILC2 type 2 cytokines but partially dependent on direct co-stimulatory interactions via ICOSL-ICOS.

Intracellular nicotinamide adenine dinucleotide promotes TNF-induced necroptosis in a sirtuin-dependent manner.

Cellular necrosis has long been regarded as an incidental and uncontrolled form of cell death. However, a regulated form of cell death termed necroptosis has been identified recently. Necroptosis can be induced by extracellular cytokines, pathogens and several pharmacological compounds, which share the property of triggering the formation of a RIPK3-containing molecular complex supporting cell death.

Animal trypanosomosis: making quality control of trypanocidal drugs possible.

African animal trypanosomosis is arguably the most important animal disease impairing livestock agricultural development in sub-Saharan Africa. In addition to vector control, the use oftrypanocidal drugs is important in controlling the impact of the disease on animal health and production in most sub-Saharan countries. However, there are no internationally agreed standards (pharmacopoeia-type monographs or documented product specifications) for the quality control of these compounds.