Local tissue expression of the cell death ligand, fas ligand, plays a central role in the development of extrapulmonary acute lung injury

Indirect acute lung injury (ALI) is a common manifestation in critically ill patients. Using a model of indirect ALI in mice, our laboratory has shown that local/pulmonary inhibition of extrinsic death receptor protein (Fas) leads to a decrease in lung inflammation and improved survival. However, it is unknown if local, i.e., autocrine/paracrine, inhibition of Fas ligand (FasL) affects Fas-expressing target cells itself or blockade of the actions of a more distal/endocrine source of FasL that accounts for these findings. To examine this, we used a model of indirect ALI in mice (dual insult of hemorrhagic shock followed 24 h later by cecal ligation and puncture, in which animals received FasL small interfering RNA (siRNA) intratracheally (local silencing) or intravenously (systemic/distal delivery) after hemorrhage. After intratracheal delivery of FasL siRNA, there was a significant decrease in inflammatory cytokines, myeloperoxidase activity, and caspase 3 activity in lung tissue along with protein leak as compared with controls. There was no difference found in these various outcome markers between those treated with intravenously administered FasL siRNA versus controls. The observation that local silencing of FasL, as opposed to distal/systemic silencing, ameliorates the effects of indirect ALI suggests not only that FasL produced in an autocrine/paracrine fashion in local tissues has pathological consequences within the lungs, but also that FasL might be a valuable pulmonary therapeutic target.     

Impaired passive maintenance and spared manipulation of internal representations in patients with schizophrenia

Working memory (WM) impairment is a core feature of schizophrenia (SZ), but the integrity of the various components of WM is unclear. After encoding, mental representations must be maintained in WM during the delay period. In addition to maintenance, manipulation of internal representation can occur in WM. It has been argued that manipulation of items in WM is more impaired than simple maintenance in SZ, but direct empirical data to support this claim have been mixed. Discrepant findings among studies might be explained by task parameters, specifically the degree to which the manipulation task places demands on encoding and maintenance processes. The present study set out to examine these components of WM in patients with SZ (n = 20) and demographically matched healthy controls (n = 19) using a spatial delayed response task (DRT) to measure maintenance processes and 2 mental rotation tasks (allocentric and egocentric) with no delay period or restriction on encoding time to measure manipulation processes. Consistent with previous findings, patients were impaired on the spatial DRT. However, patients performed equally well on the egocentric mental rotation task and were more accurate than controls on the allocentric mental rotation task as the required degree of rotation increased. These results indicated impaired maintenance and spared manipulation of representations in WM and suggest a pocket of cognitive function that might be enhanced in SZ.     

Strategies for Effective Stakeholder Engagement in Strengthening Referral Networks for Management of Hypertension Across Health Systems in Kenya

BackgroundIneffective referral networks in low- and middle-income countries hinders access to evidence-based therapies by hypertensive patients, leading to high cardiovascular mortality and morbidity. The STRENGTHS (Strengthening Referral Networks for Management of Hypertension Across Health Systems) study evaluates strategies to improve referral processes utilizing the International Association of Public Participation framework to engage stakeholders.ObjectivesThis study sought to identify and engage key stakeholders involved in referral of patients in the Ministry of Health, western Kenya.MethodsKey stakeholders involved in policy formulation, provision, or consumption of public health care service were mapped out and contacted by phone, letters, and emissaries to schedule meetings, explain research objectives, and obtain feedback.ResultsKey stakeholders identified were the Ministry of Health, the Academic Model Providing Access to Healthcare, health professionals, communities and their leadership, and patients. Engaging them resulted in permission to contact research in their areas of jurisdiction and enabled collaboration in updating care protocols with emphasis on timely and appropriate referrals.ConclusionsEarly stakeholder identification and engagement using the International Association of Public Participation model eased explanation of research objectives, building consensus, and shaping the interventions to improve the referral process.     

Locking versus non-locking plating system in the treatment of mandibular fractures: A randomized comparative study

To evaluate fracture stability and complications such as infections, need for hardware removal, malunion, and nonunion when using 2.0-mm locking plating system in fixation of mandible fractures and to compare these to those associated with the 2.0-mm non-locking plating system.A prospective clinical study was conducted in a cohort of mandible fracture patients who were randomly assigned to two groups. Patients in the non-locking group were treated with 2.0-mm non-locking plating system, and those in locking group were treated with 2.0-mm locking plating system. Fracture stability, need for maxillomandibular fixation (MMF) and postoperative complications were assessed and compared.A total of 60 patients (30 in each group) were recruited. Significant differences were found between the two groups with respect to postoperative fracture stability (P = 0.001) and need for MMF (P = 0.005). Multivariate analysis revealed that type of fixation was not the only dependent variable which affected fracture stability. There were no significant differences in postoperative complications between the two groups.The 2.0-mm locking plating system provides greater stability and early functional restoration than the 2.0-mm non-locking plating system, with similar rates of postoperative complications. Thus, it can be used as a reliable and effective treatment modality for treating mandibular fractures.     

En Bloc Excision of Phyllodes Tumor of the Breast: Radical Approach Heralds Better Outcome

IntroductionSurgery is the primary treatment of phyllodes tumor of the breast, and margins are the most important risk factor associated with local recurrence. We conducted a retrospective audit of 433 patients treated at our center.Patients and MethodsWomen who presented with phyllodes tumors between 1999 and 2017 were included in the analysis. Data was collected from the hospital medical records, telephonic interviews, and electronic mail.ResultsOf the 433 women included in this study, 177 (40.9%) had benign phyllodes tumors, 84 (19.4%) were borderline, 131 (30.3%) were malignant, and 41 (9.5%) had sarcoma. A history of previous excision was noted in 154 (35.6%) patients, of which 104 presented with local recurrence. Of the total patients, 209 (48.3%) underwent breast conservation surgery; the median pT was 6 cm. At a median follow-up of 37.9 months, the 5-year disease-free survival (DFS) was 82.9%. On multivariate analysis, the factors that impacted DFS were histology (hazard ratio, 4.1; 95% confidence interval [CI], 1.5-10.9; P = .005) and history of previous excision biopsy (hazard ratio, 3.39; 95% CI, 1.76-6.52; P < .001). We analyzed 231 women who presented without any prior excision separately, wherein at a median follow-up of 44.1 months, the DFS was 92.1% (95% CI, 92.05%-92.15%). In addition, less recurrences were noted in this cohort (5.6% [13/231] in no-excision biopsy vs. 12.5% with surgery done prior to presentation to our institute).ConclusionA previous history of excision and the histologic subtype of phyllodes tumor are factors that have an impact on DFS, thus emphasizing the need for appropriate surgical planning and en bloc excision of the phyllodes at presentation.