RationaleSepsis is a common cause of death in the intensive care unit with mortality up to 70% when accompanied by multiple organ dysfunction. Rapid diagnosis and the institution of appropriate antibiotic therapy and pressor support are therefore critical for survival. MicroRNAs are small non-coding RNAs that play an important role in the regulation of numerous cellular processes, including inflammation and immunity.ObjectivesWe hypothesized changes in expression of microRNAs during sepsis may be of diagnostic value in the intensive care unit (ICU).MethodsMassively parallel sequencing of microRNAs was utilised for screening microRNA candidates. Putative microRNAs were validated using quantitative real-time PCR (qRT-PCR). This study includes data from both a training cohort (UK) and an independent validation cohort (Sweden). A linear discriminant statistical model was employed to construct a diagnostic microRNA signature.ResultsA panel of known and novel microRNAs were detectable in the blood of patients with sepsis. After qRT-PCR validation, microRNA miR-150 and miR-4772-5p-iso were able to discriminate between patients who have systemic inflammatory response syndrome and patients with sepsis. This finding was also validated in independent cohort with an average diagnostic accuracy of 86%. Fractionating the cellular components of blood reveals miR-4772-5p-iso is expressed differentially in monocytes. Functional experiments using primary human monocytes demonstrate that it expressed in response to TLR ligation.ConclusionsTaken together, these data provide a novel microRNA signature of sepsis that should allow rapid point-of-care diagnostic assessment of patients on ICU and also provide greater insight into the pathobiology of this severe disease.

Solid organ transplantation is the standard treatment to improve both the quality of life and survival in patients with various end-stage organ diseases. The primary barrier against successful transplantation is recipient alloimmunity and the need to be maintained on immunosuppressive therapies with associated side effects. Despite such treatments in renal transplantation, after death with a functioning graft, chronic allograft dysfunction (CAD) is the most common cause of late allograft loss. Recipient recognition of donor histocompatibility antigens, via direct, indirect, and semidirect pathways, is critically dependent on the antigen-presenting cell (APC) and elicits effector responses dominated by recipient T cells. In allograft rejection, the engagement of recipient and donor cells results in recruitment of T-helper (Th) cells of the Th1 and Th17 lineage to the graft. In cases in which the alloresponse is dominated by regulatory T cells (Tregs), rejection can be prevented and the allograft tolerated with minimum or no immunosuppression. Here, we review the pathways of allorecognition that underlie CAD and the T-cell effector phenotypes elicited as part of the alloresponse. Future therapies including depletion of donor-reactive lymphocytes, costimulation blockade, negative vaccination using dendritic cell subtypes, and Treg therapy are inferred from an understanding of these mechanisms of allograft rejection.

Current data indicate the presence of both subsets during allograft rejection, although their precise role is unclear. An improved understanding of the factors that influence the differentiation and function of these cell types will assist in the development of future immunomodulatory therapies.

The sphenoid sinus is located in the center of the cranial base and is surrounded by numerous neurovascular structures. The aim of this study was to determine sphenoid sinus types and subtypes, dimensions of the sinus and cranium, and the relations of these to age and gender. Computed tomography data was obtained from 144 patients to determine right sphenoidal volume (sphVOLR), left sphenoidal volume (sphVOLL), total sphenoidal volume (sphVOLT), anteroposterior length of the sphenoid sinus (sphAP), laterolateral length of the sphenoid sinus (sphLL), head circumference (crHC), fronto-occipital length (crFO), and biparietal length (crBP), with OSIRIX software. The patients’ ages ranged between 9 and 83 years (mean age 38 ± 15.5 years). The study included 89 males (mean age 39 ± 15.5 years) and 55 females (mean age 38 ± 15.6 years). Conchal (1.4%), presellar (8.3%), sellar (23.6%), and postsellar (66.7%) type sphenoid sinuses were determined based on the extension of pneumatization around the sella turcica. Each type of sphenoid sinus was classified into the following 5 types based on the direction of pneumatization: body, full lateral, pterygoid, lesser wing, and greater wing subtypes. Mean sphAP was determined as 29.72 mm and mean sphLL as 37.73 mm. In 5 patients only (3.4%), the sphenoid sinus was not divided into right and left by the intersphenoidal septum. The variations in the extensions of pneumatization of the sphenoid sinus and its dimensions might be used to estimate the selection of a surgical approach to lesions bordering the sinus.

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Summary The use of preimplantation kidney biopsies (PIKBs) to aid deceased donor kidney utilization decisions is controversial. Outcomes of transplants that had been biopsied after the decision had been made to implant were analysed, in order to determine the association between chronic histological changes at implantation and graft outcomes. A retrospective analysis of transplants between the year range 2006–2015 was performed. Karpinski scores on biopsies were collected, and graft outcomes were analysed using univariate and multivariable techniques. Also, Karpinski scores from single and dual kidney transplants from older donors were examined to determine if knowledge of the score preoperatively would have altered utilization. Four hundred and eight single kidneys were transplanted. Although kidneys with scores >4 had lower 1‐ and 3‐year median (IQR) estimated glomerular filtration rates (eGFRs) than those scoring 0–4 (51 (37–66) vs. 35 (26–52) ml/min/1.73 m2, P < 0.001, and 52 (34–64) vs. 35 (24–52) ml/min/1.73 m2, P < 0.001, respectively), there was no significant association between Karpinski score and death‐censored graft survival on univariate or multivariable analyses. The utilization analysis (75 single and 25 dual kidney transplant recipients) suggested that systematic use of PIKBs would have resulted in 29% fewer patients being transplanted. This analysis does not support the systematic use of PIKBs to determine deceased donor kidney utilization.

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This study was carried out to investigate the bony structures relevant to skull of roe deer, sheep and goat. The skull of five sheep weighing 45-50 kg, three goat weighing 50-60 kg and five roe deer weighing 20-25 kg were used in this study. Macerations of the cranium were performed by the boiling method. The skull of the roe deer was notably similar to that of sheep with the presence of external lacrimal fossa, and to the goat with due to the presence of two points (lateral and medial) on the septal process and a significant fissure formed between the nasal, lacrimal, frontal and maxillary bones. In addition to these similarities, the formations which were specific to the roe deer were structures such as the number and position of the lacrimal foramen and presence of an uncertain muscular tubercle in the basilar portion of the occipital bone. In addition, the craniometric parameters specific to the roe deer’s skull were determined as the zygomatic, interorbital, neurocranium and nasal lengths