Venous thromboembolism after Diaphragm Pacing in amyotrophic lateral sclerosis

Introduction: Patients with amyotrophic lateral sclerosis (ALS) are prone to venous thromboembolism (VTE) and secondary complications. Because there is an increased incidence of VTE after surgical procedures, placement of a Diaphragm Pacing System (DPS) in ALS patients as treatment for respiratory muscle weakness could potentially increase the incidence of VTE, especially in patients with limited mobility. Methods: We implanted a DPS in 10 ALS patients who met the criteria for this procedure. They underwent a preoperative evaluation as recommended by the guidelines. Results: We report 2 patients with no symptoms of deep vein thrombosis (DVT) before the surgical procedure who then developed perioperative VTE. Conclusions: These patients highlight the need to consider preoperative screening for DVT and postoperative thromboprophylaxis in high‐risk ALS patients who undergo DPS placement. Muscle Nerve 50 : 863–865, 2014     

The clinical landmark of infraorbital foramen in Chinese population: a prospective measurement study

Background

Infraorbital nerve block can only be administered effectively with good knowledge of the location of the infraorbital foramen (IOF). In this article, we will describe the clinical landmark of the IOF with references to the infraorbital rim (IOR), mid-pupillary line (MPL), and facial midline (FML).

Methods

In our division, maxillary swing approach was adopted for the access of the nasopharynx and skull base. Through a Weber-Ferguson-Longmire incision, the maxilla was freed from its bony connections and swung out to expose the skull base. With this approach, the infraorbital foramen and nerve were identified under direct vision. Prospective measurements were taken intraoperatively on a series of patients who underwent maxillary swing operation. The distances between the IOF and various reference points (IOR, MPL, and FML) were measured with caliper. Means, standard deviations, and ranges were determined.

Results

From April 2009 to October 2012, 30 patients were included in this study. The locations of 30 infraorbital foramina were analyzed. The distances between IOF and IOR, MPL, and FML ranged from 8 to 12 (mean 9.6?±?1.3) mm, 4 to 14 (mean 9.3?±?2.4) mm, and 24 to 38 (mean 32.7?±?3.4) mm, respectively.

Conclusions

To our knowledge, this is the first study in the literature demonstrating the clinical landmark of IOF on living persons and adopting MPL as a reference point. We believe that the IOR and MPL are convenient reference points for the accurate localization of IOF. Level of Evidence: Level IV, diagnostic study.     

Understanding Misdemeanor Enforcement: The Roles of Calls for Service and Community Characteristics

This study examines the roles of calls for service (i.e., police-related 911 calls) and community characteristics in explaining variation in enforcement rates for low-level, misdemeanor offenses, which make up the large majority of police enforcement activity. The study site is Prince George's County, Maryland, and the unit of analysis is the police department's 65 patrol beats, studied over a 10-year period, during 2006–2015. Overall, misdemeanor enforcement rates vary at the beat level, and that variation can be largely explained using a combination of indicators about community characteristics and calls for service. The findings indicate, though, that the calls for service rate is the most important variable in explaining misdemeanor enforcement variation. These findings inform both future research on police activity, and current policy debates about what drives enforcement rates and the role of discretion in enforcement outcomes.     

Evolution of neuronal and glial tau isoforms in chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy characterized by accumulation of hyperphosphorylated tau (p‐tau) in perivascular aggregates in neurons and glia at the depths of neocortical sulci and progresses to diffuse neocortical, allocortical and brainstem structures. The strongest risk factor is exposure to repetitive head impacts acquired most commonly through contact sports and military service. Given that CTE can only be definitively diagnosed after death, a better understanding of the cellular and molecular changes in CTE brains may lead to identification of mechanisms that could be used for novel biomarkers, monitoring progression or therapeutic development. Disruption of alternative pre‐mRNA splicing of tau mRNA plays a pathogenic role in tauopathy, with multiple characteristic patterns of isoform accumulation varying among tauopathies. Limited data are available on CTE, particularly at early stages. Using biochemical and histological approaches, we performed a detailed characterization of tau isoform signatures in post‐mortem human brain tissue from individuals with a range of CTE stages (n = 99). In immunoblot analyses, severity was associated with decreased total monomeric tau and increased total oligomeric tau. Immunoblot with isoform‐specific antisera revealed that oligomeric tau with three and four microtubule binding domain repeats (3R and 4R) also increased with CTE severity. Similarly, immunohistochemical studies revealed p‐tau accumulation consisting of both 3R and 4R in perivascular lesions. When the ratio of 4R:3R was analyzed, there was mixed expression throughout CTE stages, although 4R predominated in early CTE stages (I‐II), a 3R shift was observed in later stages (III‐IV). While neurons were found to contain both 3R and 4R, astrocytes only contained 4R. These 4R‐positive cells were exclusively neuronal at early stages. Overall, these findings demonstrate that CTE is a mixed 4R/3R tauopathy. Furthermore, histologic analysis reveals a progressive shift in tau isoforms that correlates with CTE stage and extent of neuronal pathology.     

EFTUD2 missense variants disrupt protein function and splicing in mandibulofacial dysostosis Guion‐Almeida type

Pathogenic variants in the core spliceosome U5 small nuclear ribonucleoprotein gene EFTUD2/SNU114 cause the craniofacial disorder mandibulofacial dysostosis Guion‐Almeida type (MFDGA). MFDGA‐associated variants in EFTUD2 comprise large deletions encompassing EFTUD2, intragenic deletions and single nucleotide truncating or missense variants. These variants are predicted to result in haploinsufficiency by loss‐of‐function of the variant allele. While the contribution of deletions within EFTUD2 to allele loss‐of‐function are self‐evident, the mechanisms by which missense variants are disease‐causing have not been characterized functionally. Combining bioinformatics software prediction, yeast functional growth assays, and a minigene (MG) splicing assay, we have characterized how MFDGA missense variants result in EFTUD2 loss‐of‐function. Only four of 19 assessed missense variants cause EFTUD2 loss‐of‐function through altered protein function when modeled in yeast. Of the remaining 15 missense variants, five altered the normal splicing pattern of EFTUD2 pre‐messenger RNA predominantly through exon skipping or cryptic splice site activation, leading to the introduction of a premature termination codon. Comparison of bioinformatic predictors for each missense variant revealed a disparity amongst different software packages and, in many cases, an inability to correctly predict changes in splicing subsequently determined by MG interrogation. This study highlights the need for laboratory‐based validation of bioinformatic predictions for EFTUD2 missense variants.     

Fearlessness About Death is Related to Diminished Late Positive Potential Responses When Viewing Threatening and Mutilation Images in Suicidal Ideators

Cognitive Therapy and Research - Very few people who desire death by suicide ever make a suicide attempt, highlighting the importance of determining factors that influence the capability to enact...     

Intermediate Susceptibility to Ciprofloxacin among Salmonella enterica Serovar Typhi Isolates in Lima,Peru

Thirty-three Salmonella enterica serovar Typhi blood isolates from Lima, Peru (2008 to 2012), were fully susceptible to trimethoprim-sulfamethoxazole, chloramphenicol, ceftriaxone, and tetracycline; 8/33 (24.2%) showed intermediate susceptibility to ciprofloxacin carrying mutations in the quinolone resistance-determining region of the gyrA gene (Ser83-Phe and Asp87-Asn) and in the gyrB gene (Ser464-Phe).     

Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome.