Closed Collaborative Surgical Intensive Care Unit Modeling and Its Association With Trauma Patient Outcomes.

INTRODUCTION: The optimization of intensive care unit (ICU) care impacts clinical outcomes and resource utilization. In 2017, our surgical ICU (SICU) adopted a "closed-collaborative" model. The aim of this study is to compare patient outcomes in the closed-collaborative model versus the previous open model in a cohort of trauma surgical patients admitted to our adult level 1 trauma center. METHODS: A retrospective review of trauma patients in the SICU from August 1, 2015 to July 31, 2019 was performed. Patients were divided into those admitted prior to August 1, 2017 (the "open" cohort) and those admitted after August 1, 2017 (the "closed-collaborative" cohort). Demographic variables and clinical outcomes were analyzed. Trauma severity was assessed using injury severity score (ISS). RESULTS: We identified 1669 patients (O: 895; C: 774). While no differences in demographics were observed, the closed-collaborative cohort had a higher overall ISS (O: 21.5 ± 12.14; C: 25.10 ± 2.72; P < 0.0001). There were no significant differences between the two cohorts in the incidence of strokes (O: 1.90%; C: 2.58%, P = 0.3435), pulmonary embolism (O: 0.78%; C: 0.65%; P = 0.7427), sepsis (O: 5.25%; C: 7.49%; P = 0.0599), median ICU charges (O: $7784.50; C: $8986.53; P = 0.5286), mortality (O: 11.40%; C: 13.18%; P = 0.2678), or ICU length of stay (LOS) (O: 4.85 ± 6.23; C: 4.37 ± 4.94; P = 0.0795). CONCLUSIONS: Patients in the closed-collaborative cohort had similar clinical outcomes despite having a sicker cohort of patients. We hypothesize that the closed-collaborative ICU model was able to maintain equivalent outcomes due to the dedicated multidisciplinary critical care team caring for these patients. Further research is warranted to determine the optimal model of ICU care for trauma patients.

The equine immune response to Streptococcus equi subspecies zooepidemicus during uterine infection.

The purpose of this study was to describe strain-specific immune responses to Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) during uterine infection in horses. Five isolates of S. zooepidemicus were differentiated into four strains antigenically by bactericidal testing in blood of 12 horses, and genetically by pulsed-field gel electrophoresis. Eight healthy mares were then divided into two groups, each inoculated with one strain intrauterinely on three successive oestrous cycles followed by a second strain for three successive cycles, first and second strains being reversed for each group. Immune responses to both strains were assessed by bactericidal testing and immunoblotting over eight cycles. Both techniques indicated that immune responses to each strain arose at different times. Immunoblots showed greater binding to the first inoculated strain than to the second (P < 0.05). These data confirm that immune responses to S. zooepidemicus during uterine infection are partly strain-specific.

RNA interference: the molecular immune system.

Introduction of double-stranded RNA (dsRNA) into cells expressing a homologous gene triggers RNA interference (RNAi), or RNA-based gene silencing (RBGS). The dsRNA degrades corresponding host mRNA into small interfering RNAs (siRNAs) by a protein complex containing Dicer. siRNAs in turn are incorporated into the RNA-induced silencing complex (RISC) that includes helicase, RecA, and exo- and endo-nucleases as well as other proteins. Following its assembly, the RISC guides the RNA degradation machinery to the target RNAs and cleaves the cognate target RNA in a sequence-specific, siRNA-dependent manner. RNAi has now been documented in a wide variety of organisms, including plants, fungi, flies, worms, and more recently, higher mammals. In eukaryotes, dsRNA directed against a range of viruses (i.e., HIV-1, RSV, HPV, poliovirus and others) and endogenous genes can induce sequence-specific inhibition of gene expression. In invertebrates, RNAi can be efficiently triggered by either long dsRNAs or 21- to 23-nt-long siRNAs. However, in jawed vertebrates, dsRNA longer than 30 bp can induce interferon and thus trigger undesirable side effects instead of initiating RNAi. siRNAs have been shown to act as potent inducers of RNAi in cultured mammalian cells. Many investigators have suggested that siRNAs may have evolved as a normal defense against endogenous and exogenous transposons and retroelements. Through a combination of genetic and biochemical approaches, some of the mechanisms underlying RNAi have been described. Recent data in C. elegans shows that two homologs of siRNAs, microRNAs (miRNAs) and tiny noncoding RNAs (tncRNAs) are endogenously expressed. However, many aspects of RNAi-induced gene silencing, including its origins and the selective pressures which maintain it, remain undefined. Its evolutionary history may pass through the more primitive immune functions of prokaryotes involving restriction enzymes that degrade plasmid DNA molecules that enter bacterial cells. RNAi has evolved further among eukaryotes, in which its wide distribution suggests early origins. RNAi seems to be involved in a variety of regulatory and immune functions that may differ among various kingdoms and phyla. We present here proposed mechanisms by which RBGS protects the host against endogenous and exogenous transposons and retroelements. The potential for therapeutic application of RBGS technology in treating viral infections such as HIV is also discussed.

A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells.

Dendritic cells (DCs) are capable of cross-presenting exogenous Ag to CD8(+) CTLs. Detection of microbial products by Toll-like receptors (TLRs) leads to activation of DCs and subsequent orchestration of an adaptive immune response. We hypothesized that microbial TLR ligands could activate DCs to cross-present Ag to CTLs. Using DCs and CTLs in an in vitro cross-presentation system, we show that a subset of microbial TLR ligands, namely ligands of TLR3 (poly(inosinic-cytidylic) acid) and TLR9 (immunostimulatory CpG DNA), induces cross-presentation. In contrast to presentation of Ag to CD4(+) T cells by immature DCs, TLR-induced cross-presentation is mediated by mature DCs, is independent of endosomal acidification, and relies on cytosolic Ag processing machinery.

Cutting edge: a crucial role for B7-CD28 in transmitting T help from APC to CTL.

Although APC activation via CD40-CD40L signaling plays a critical role in enabling CD4(+) T cells to provide the "help" necessary for cross-priming of naive CTL, it is unclear how this makes the APC competent for priming. We have investigated the roles of B7-1/B7-2 and their receptors [corrected] CD28/CTLA-4 in cross-priming of CD4-dependent CTL in vivo. We find that both CD28 and B7-1/B7-2 are required for CD40-activated APC to cross-prime CTL, and that priming by CD40-activated APC was prevented by blockade of CD28. Conversely, augmenting CD28 signals with an agonistic Ab bypassed the requirement for CD4(+) T help or CD40 activation. Interestingly, blockade of the negative regulatory B7 receptor CTLA-4 failed to prime CTL in the absence of T help. These results support a model in which activation-induced up-regulation of B7 molecules on APC leads to increased CD28 signaling and a commitment to cross-priming of CD4-dependent CTL.

HLA class I polymorphism has a dual impact on ligand binding and chaperone interaction.

This article will describe coordinated analyses of how amino acid substitutions in the HLA class I antigen binding groove modify chaperone interaction and peptide ligand presentation. By parallel testing of ligand presentation and chaperone interaction with a series of natural HLA-B subtypes, this study has discovered that position 116 of the HLA-B15 class I heavy chain is pivotal in both peptide selection and control of interaction between the assembly complex and the class I heavy chain. Correlated with these qualitative differences in peptide selection and chaperone association are quantitative differences in the expression levels of the HLA molecules at the cell surface. These parallel studies, therefore, demonstrate that particular HLA class I polymorphisms can simultaneously influence ligand presentation and interaction with intracellular chaperones.

CD40L blockade prevents autoimmune diabetes by induction of bitypic NK/DC regulatory cells.

Systemic treatment with antibody to CD40 ligand (aCD40L) can prevent autoimmunity and transplant rejection in several animal models and is currently under evaluation in clinical trials. While it is known that aCD40L administration inhibits expansion and effector functions of aggressive T cells, it is still unclear whether additional regulatory mechanisms are operative. Here we demonstrate that a single episode of CD40L blockade during development of the autoaggressive immune response completely prevented autoimmune disease in the RIP-LCMV mouse model for virally induced type 1 diabetes. Interestingly, protection could be transferred by a highly potent, bitypic cell population sharing phenotypic and functional properties of both natural killer (NK) and dendritic cells (DC). Furthermore, protection of prediabetic recipients was autoantigen specific and did not result in generalized immunosuppression. The origin, function, and therapeutic potential of these bitypic NK/DC regulatory cells is discussed.

Field evaluation of a transportable open-path FTIR spectrometer for real-time air monitoring.

To effectively and accurately evaluate human exposures to chemicals, it is important to quantify mixtures of chemicals in air, at low levels, and in real time. The purpose of this study was to evaluate, in the field, a prototype of a new transportable instrument that can fill an important gap in methods available to industrial hygienists. This instrument is a cross between extractive and open-path Fourier Transform Infrared spectrometers and measures chemicals passively and in real time in the vicinity of the breathing zone. The spectrometer has a folded optical path that can be enclosed, similar to an extractive system. The enclosure can be removed, enabling the optical path to be open to the atmosphere; thus, the instrument could be operated as an open-path spectrometer. A field study was conducted in three different occupational settings, including a prosthodontics dental laboratory, a surgery recovery area, and a cytology laboratory. Chemicals that were identified and quantified included methyl methacrylate, nitrous oxide, xylene isomers, toluene, and ethanol. Simultaneous side-by-side sampling was conducted with the prototype instrument and recognized National Institute of Occupational Safety and Health (NIOSH) analytical methods. The distinct infrared "fingerprint" of each chemical made identification and quantification of multiple chemicals possible with the prototype instrument. This attribute allowed the industrial hygienist to quantify short-term exposures and ceiling levels, correlate work practices with concentration levels, evaluate the effectiveness of engineering controls, and identify the presence of unexpected compounds. There was no significant difference between the mean time-weighted averages (TWAs) of the prototype instrument and traditional methods (p > 0.03). Regression analysis found good correlation between the two methods with no significant differences between the slope and unity and between the y-intercept and zero (p > 0.03). The technology and design of the prototype instrument incorporated a unique combination of features and advantages not found in other methods or instruments. The instrument produced results comparable to recognized analytical methods under field conditions and shows promise as a powerful tool in industrial hygiene air monitoring applications.

Finding health information on the Internet: health professionals.

This article discusses some of the key problems that clinicians encounter when searching the Internet for health information. Guidance is provided on how best to search the Internet to find high-quality information and resources. The Internet is a dynamic and valuable source of information for health professionals, but information accessed through the Internet should be critically evaluated before being applied to practice.

Finding health information on the Internet: health consumers.

The quality of health information on the Internet is extremely variable. This article highlights some of the problems consumers encounter when searching for health information and suggests ways in which these can be overcome.