Outcomes of Operatively Treated Acute Knee Dislocations

Knee dislocation is a complex and rare injury often presenting in the context of high velocity trauma. The aim of this study is to establish the subjective outcomes of surgically treated knee dislocations. A total of 20 knees dislocations treated by open repair were reviewed. Their progress and outcomes were assessed by using a modified Lysholm score questionnaire. Data was obtained on patient demographics, details of injury, investigation, treatment, rehabilitation, 24 months objective outcome and subjective outcomes. Six patients had a vascular deficit and six had neurological deficits. The median range of motion was 0°-100°. Patients with an initially lower pre-injury level of function were able to return an activity level comparable to their pre-injury status. 22% of competitive athletes retuned to competitive sports. 38% of patients undertaking heavy activity returned to comparable pre-injury level of activity and 67% of patients undertaking moderate level of activity before injury returned to a comparable level after repair. 68% regularly had problems running, 70% problem squatting, 40% swelling and 42% problem with stairs. Most patients however did not have locking of the knee or problems with knees giving way. Patients pain scores decreased over time to an acceptable level. Despite the severity of the injury, majority of patients achieved a satisfactory outcome, although none of the patients reached the same level of function as before the injury. 80% of the patients were satisfied with their outcome. All dissatisfied patients suffered postoperative complications

Optical Imaging of Bacterial Infections

The rise in multidrug resistant (MDR) bacteria has become a global crisis. Rapid and accurate diagnosis of infection will facilitate antibiotic stewardship and preserve our ability to treat and cure patients from bacterial infection. Direct in situ imaging of bacteria offers the prospect of accurately diagnosing disease and monitoring patient outcomes and response to treatment in real-time. There have been many recent advances in the field of optical imaging of infection; namely in specific probe and fluorophore design. This combined with the advances in imaging device technology render direct optical imaging of infection a feasible approach for accurate diagnosis in the clinic. Despite this, there are currently no licensed molecular probes for clinical optical imaging of infection. Here we report some of the most promising and interesting probes and approaches under development for this purpose, which have been evaluated in in vivo models within the laboratory setting

Diacylglycerol regulates acute hypoxic pulmonary vasoconstriction via TRPC6

Background: Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism of the lung that matches blood perfusion to alveolar ventilation to optimize gas exchange. Recently we have demonstrated that acute but not sustained HPV is critically dependent on the classical transient receptor potential 6 (TRPC6) channel. However, the mechanism of TRPC6 activation during acute HPV remains elusive. We hypothesize that a diacylglycerol (DAG)-dependent activation of TRPC6 regulates acute HPV. Methods: We investigated the effect of the DAG analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) on normoxic vascular tone in isolated perfused and ventilated mouse lungs from TRPC6-deficient and wild-type mice. Moreover, the effects of OAG, the DAG kinase inhibitor R59949 and the phospholipase C inhibitor U73122 on the strength of HPV were investigated compared to those on non-hypoxia-induced vasoconstriction elicited by the thromboxane mimeticum U46619. Results: OAG increased normoxic vascular tone in lungs from wild-type mice, but not in lungs from TRPC6-deficient mice. Under conditions of repetitive hypoxic ventilation, OAG as well as R59949 dose-dependently attenuated the strength of acute HPV whereas U46619-induced vasoconstrictions were not reduced. Like OAG, R59949 mimicked HPV, since it induced a dose-dependent vasoconstriction during normoxic ventilation. In contrast, U73122, a blocker of DAG synthesis, inhibited acute HPV whereas U73343, the inactive form of U73122, had no effect on HPV. Conclusion: These findings support the conclusion that the TRPC6-dependency of acute HPV is induced via DAG

Posttraumatic stress disorder (PTSD) in children after paediatric intensive care treatment compared to children who survived a major fire disaster

<p>Abstract</p> <p>Background</p> <p>The goals were to determine the presence of posttraumatic stress disorder (PTSD) in children after paediatric intensive care treatment, to identify risk factors for PTSD, and to compare this data with data from a major fire disaster in the Netherlands.</p> <p>Methods</p> <p>Children completed the Dutch Children's Responses to Trauma Inventory at three and nine months after discharge from the paediatric intensive care unit (PICU). Comparison data were available from 355 children survivors who completed the same questionnaire 10 months after a major fire disaster.</p> <p>Results</p> <p>Thirty-six children aged eight to 17 years completed questionnaires at three month follow-up, nine month follow-up, or both. More than one third (34.5%) of the children had subclinical PTSD, while 13.8% were likely to meet criteria for PTSD. Maternal PTSD was the strongest predictor for child PTSD. There were no significant differences in (subclinical) PTSD symptoms either over time or compared to symptoms of survivors from the fire disaster.</p> <p>Conclusion</p> <p>This study shows that a considerable number of children have persistent PTSD after PICU treatment. Prevention of PTSD is important to minimize the profound adverse effects that PTSD can have on children's well-being and future development.</p

Emerging role of the calcium-activated, small conductance, SK3 K ⁺ channel in distal tubule function: Regulation by TRPV4

The Ca2+-activated, maxi-K (BK) K+ channel, with low Ca2+-binding affinity, is expressed in the distal tubule of the nephron and contributes to flow-dependent K+ secretion. In the present study we demonstrate that the Ca2+-activated, SK3 (KCa2.3) K + channel, with high Ca2+-binding affinity, is also expressed in the mouse kidney (RT-PCR, immunoblots). Immunohistochemical evaluations using tubule specific markers demonstrate significant expression of SK3 in the distal tubule and the entire collecting duct system, including the connecting tubule (CNT) and cortical collecting duct (CCD). In CNT and CCD, main sites for K+ secretion, the highest levels of expression were along the apical (luminal) cell membranes, including for both principal cells (PCs) and intercalated cells (ICs), posturing the channel for Ca2+- dependent K+ secretion. Fluorescent assessment of cell membrane potential in native, split-opened CCD, demonstrated that selective activation of the Ca2+-permeable TRPV4 channel, thereby inducing Ca2+ influx and elevating intracellular Ca2+ levels, activated both the SK3 channel and the BK channel leading to hyperpolarization of the cell membrane. The hyperpolarization response was decreased to a similar extent by either inhibition of SK3 channel with the selective SK antagonist, apamin, or by inhibition of the BK channel with the selective antagonist, iberiotoxin (IbTX). Addition of both inhibitors produced a further depolarization, indicating cooperative effects of the two channels on Vm. It is concluded that SK3 is functionally expressed in the distal nephron and collecting ducts where induction of TRPV4-mediated Ca2+ influx, leading to elevated intracellular Ca2+ levels, activates this high Ca2+- affinity K+ channel. Further, with sites of expression localized to the apical cell membrane, especially in the CNT and CCD, SK3 is poised to be a key pathway for Ca2+-dependent regulation of membrane potential and K+ secretion. © 2014 Berrout et al

Functional annotation of the transcriptome of Sorghum bicolor in response to osmotic stress and abscisic acid

<p>Abstract</p> <p>Background</p> <p>Higher plants exhibit remarkable phenotypic plasticity allowing them to adapt to an extensive range of environmental conditions. Sorghum is a cereal crop that exhibits exceptional tolerance to adverse conditions, in particular, water-limiting environments. This study utilized next generation sequencing (NGS) technology to examine the transcriptome of sorghum plants challenged with osmotic stress and exogenous abscisic acid (ABA) in order to elucidate genes and gene networks that contribute to sorghum's tolerance to water-limiting environments with a long-term aim of developing strategies to improve plant productivity under drought.</p> <p>Results</p> <p>RNA-Seq results revealed transcriptional activity of 28,335 unique genes from sorghum root and shoot tissues subjected to polyethylene glycol (PEG)-induced osmotic stress or exogenous ABA. Differential gene expression analyses in response to osmotic stress and ABA revealed a strong interplay among various metabolic pathways including abscisic acid and 13-lipoxygenase, salicylic acid, jasmonic acid, and plant defense pathways. Transcription factor analysis indicated that groups of genes may be co-regulated by similar regulatory sequences to which the expressed transcription factors bind. We successfully exploited the data presented here in conjunction with published transcriptome analyses for rice, maize, and Arabidopsis to discover more than 50 differentially expressed, drought-responsive gene orthologs for which no function had been previously ascribed.</p> <p>Conclusions</p> <p>The present study provides an initial assemblage of sorghum genes and gene networks regulated by osmotic stress and hormonal treatment. We are providing an RNA-Seq data set and an initial collection of transcription factors, which offer a preliminary look into the cascade of global gene expression patterns that arise in a drought tolerant crop subjected to abiotic stress. These resources will allow scientists to query gene expression and functional annotation in response to drought.</p