Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles

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Biology‐Driven Gene‐Gene Interaction Analysis of Age‐Related Cataract in the eMERGE Network

Bioinformatics approaches to examine gene‐gene models provide a means to discover interactions between multiple genes that underlie complex disease. Extensive computational demands and adjusting for multiple testing make uncovering genetic interactions a challenge. Here, we address these issues using our knowledge‐driven filtering method, Biofilter, to identify putative single nucleotide polymorphism (SNP) interaction models for cataract susceptibility, thereby reducing the number of models for analysis. Models were evaluated in 3,377 European Americans (1,185 controls, 2,192 cases) from the Marshfield Clinic, a study site of the Electronic Medical Records and Genomics (eMERGE) Network, using logistic regression. All statistically significant models from the Marshfield Clinic were then evaluated in an independent dataset of 4,311 individuals (742 controls, 3,569 cases), using independent samples from additional study sites in the eMERGE Network: Mayo Clinic, Group Health/University of Washington, Vanderbilt University Medical Center, and Geisinger Health System. Eighty‐three SNP‐SNP models replicated in the independent dataset at likelihood ratio test P < 0.05. Among the most significant replicating models was rs12597188 (intron of CDH1)–rs11564445 (intron of CTNNB1). These genes are known to be involved in processes that include: cell‐to‐cell adhesion signaling, cell‐cell junction organization, and cell‐cell communication. Further Biofilter analysis of all replicating models revealed a number of common functions among the genes harboring the 83 replicating SNP‐SNP models, which included signal transduction and PI3K‐Akt signaling pathway. These findings demonstrate the utility of Biofilter as a biology‐driven method, applicable for any genome‐wide association study dataset.     

Fluid resuscitation in pre-hospital management of septic shock

Background

Septic shock is associated with hypovolemia resulting in organs failure and poor prognosis. The first step in hemodynamic resuscitation relies on early fluid expansion. In this study, we describe qualitative and quantitative fluid resuscitation of septic shock initially managed in a pre-hospital setting by a mobile intensive care unit.

Regurgitations in a Lamb with Acute Coenurosis-A case Report

Coenurosis is a disease of the central nervous system in sheep, caused by Coenurus cerebralis, the larval stage of Multiceps multiceps, which inhabits the small intestine of Canidae. A case of regurgitations in a 2.5 month old lamb with acute coenurosis is being reported. The lamb was presented with a sudden onset of ataxia and regurgitations for 10 days. The post-mortem examination revealed 4 immature C. cerebralis cysts between 0.5 and 1.5 cm in diameter located in the brainstem and cerebellum, and histopathological examination revealed multifocal pyogranulomatous meningoencephalitis, so a diagnosis of acute coenurosis was established. Thus, acute coenurosis should be included in the differential diagnosis of regurgitations in lambs.     

The diagnosis of Gestational Diabetes Mellitus and its impact on In Vitro Fertilization pregnancies. A pilot study

BackgroundIn Vitro Fertilization (IVF) is increasingly becoming a necessary mode of reproduction. This high risk group is prone to Gestational Diabetes Mellitus (GDM) which further exposes these pregnancies to an increased risk of adverse outcomes. In light of the limited data in the current literature, further investigation is needed regarding the time of GDM diagnosis in IVF pregnancies as well as the outcome of IVF pregnancies complicated by GDM.MethodsIn this three center pilot cross sectional study, the data of 101 singleton IVF pregnancies complicated by GDM were analyzed. Prompt GDM diagnosis in IVF pregnancies was accomplished by self-blood glucose monitoring (SMBG) from the first antenatal visit and confirmed by an OGTT. To evaluate pregnancy outcome, maternal and fetal complications in the 101 GDM IVF group was compared to 101 IVF as well as 101 spontaneous conceptions (SC). The three groups were matched by age. The effect of demographic and glycemic parameters on the outcome of GDM IVF pregnancies was investigated.ResultsGDM diagnosis was made before the 24th week in 37.6% of the GDM IVF group. The week of delivery was earlier for the GDM IVF group (37 ± 1.7) relative to the IVF (37.9 ± 0.9, p < 0.001) and the SC group (38.1 ± 0.8, p < 0.001). GDM IVF pregnancies exhibited greater preeclampsia rates and 84.8% underwent caesarian section. No significant difference regarding LGA and SGA birth weights was found. Complications of GDM IVF pregnancies were associated with the 1-h postprandial BG (r = 0.267, p = 0.007).ConclusionGDM screening in IVF pregnancies may be considered earlier than the 24th week. IVF pregnancies affected by GDM are prone to increased maternal and fetal complications which are associated with 1-h postprandial BG.     

Thoracoscopic surgery in elderly lung cancer patients

Age is a recognized risk factor for death after thoracotomy in elderly patients with lung cancer. Among other factors, the genesis of this risk is the physiologic debilitation that occurs after division of the intrathoracic respiratory muscles during thoracotomy, as well as the loss of lung tissue after lung resection. Recent advances in video-assisted thoracic surgery (VATS) techniques provide an alternative to standard thoracotomy in elderly lung cancer patients, resulting in decreased recovery times and fewer perioperative complications. Likewise, smaller lung resections (VATS-guided limited wedge resection versus lobectomy with thoracotomy) can be adequate oncologic procedures in patients with a limited life expectancy but resectable disease. We studied these alternative procedures in a cohort of thoracic surgical patients at the Brigham and Women's Hospital in Boston, MA. Proposed investigations of the psychosocial implications of thoracic surgery in the elderly, irrespective of the safety of these maneuvers, are addressed.