Pain after posterolateral versus nerve-sparing thoracotomy: A randomized trial

Objectives

Post-thoracotomy pain leads to patient discomfort, pulmonary complications, and increased analgesic use. Intercostal nerve injury during thoracotomy or its entrapment during closure can contribute to post-thoracotomy pain. We hypothesized that a modified technique of posterolateral thoracotomy and closure, preserving the intercostal neurovascular bundle, would reduce acute and chronic post-thoracotomy pain.

Motor and language deficits correlate with resting state functional magnetic resonance imaging networks in patients with brain tumors

Background and purpose

Evidence of pre-operative resting state functional magnetic resonance (RS-fMRI) validation by correlating it with clinical pre-operative status in brain tumor patients is scarce. Our aim was to validate the functional relevance of RS-fMRI by investigating the association between RS-fMRI and pre-operative motor and language function performance in patients with brain tumor.

Dose optimization of moxifloxacin and linezolid against tuberculosis using mathematical modeling and simulation

Introduction

There is an urgent need for new anti-tuberculosis (TB) drugs and optimization of current TB treatment. Moxifloxacin and linezolid are valuable options for the treatment of drug-resistant TB; however, it is crucial to find a dose at which these drugs not only show high efficacy but also suppress the development of further drug resistance.

Detection of Memory B Activity Against a Therapeutic Protein in Treatment-Naïve Subjects

Bridging immunoassays commonly used to detect and characterize immunogenicity during biologic development do not provide direct information on the presence or development of a memory anti-drug antibody (ADA) response. In this study, a B cell ELISPOT assay method was used to evaluate pre-existing ADA for anti-TNFR1 domain antibody, GSK1995057, an experimental biologic in treatment naive subjects. This assay utilized a 7-day activation of PBMCs by a combination of GSK1995057 (antigen) and polyclonal stimulator followed by GSK1995057-specific ELISPOT for the enumeration of memory B cells that have differentiated into antibody secreting cells (ASC) in vitro. We demonstrated that GSK1995057-specific ASC were detectable in treatment-naïve subjects with pre-existing ADA; the frequency of drug-specific ASC was low and ranged from 1 to 10 spot forming units (SFU) per million cells. Interestingly, the frequency of drug-specific ASC correlated with the ADA level measured using an in vitro ADA assay. We further confirmed that the ASC originated from CD27⁺ memory B cells, not from CD27^?-naïve B cells. Our data demonstrated the utility of the B cell ELISPOT method in therapeutic protein immunogenicity evaluation, providing a novel way to confirm and characterize the cell population producing pre-existing ADA. This novel application of a B cell ELISPOT assay informs and characterizes immune memory activity regarding incidence and magnitude associated with a pre-existing ADA response.     

New molecular diagnostic trends and biomarkers for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disorder. Two forms are recognized, familial (FALS) that accounts for 5–10% of ALS cases, and sporadic (SALS) that accounts for the rest. Early diagnosis of ALS is important because it improves their therapeutic efficacy. Current diagnosis is based on clinical assessment and requires approximately 12 months, leading to a significant delay in drug administration. Therefore, new methods are required for the earlier diagnosis of ALS. Screening for pathogenic variants in known ALS‐associated genes is already exploited as a diagnostic tool in ALS but cannot be applied for population‐based screening. New circulating biomarkers (proteins or small molecules) are needed for initial screening, whereas specific diagnostic methods can be applied to confirm the presence of pathogenic variants in the selected population subgroup. Lipids appear as promising biomarkers for population‐based screening and for monitoring disease progression. Genetic analysis can also assist in the prediction of disease progression by analyzing disease‐modifying genes, for example, EPHA4 and CHGB. Furthermore, molecular diagnosis will aid the stratification of ALS patients for improved pharmacological approaches. Here, we discuss current and novel diagnostic strategies and how they can be applied to revolutionize the field of ALS molecular diagnosis.     

Preliminary Associations among Relational Victimization,Targeted Rejection,and Suicidality in Adolescents: A Prospective Study

This study examined associations between multiple types of interpersonal and noninterpersonal stressors and the subsequent occurrence of suicide ideation and attempts among female adolescents. Adolescents ages 12 to 18 years old (n = 160) at elevated risk for suicidal thoughts and behaviors were followed for 18 months, divided into two 9-month epochs for data analysis (Periods 1 and 2). Exposure to acute relational victimization, targeted rejection, nonspecified interpersonal, and noninterpersonal life stressors over the first 9-month epoch (Period 1) was assessed using semistructured interviews and an independent life stress rating team. Participants also completed phone-based semistructured interviews of suicidal thoughts and behaviors. Preliminary analyses showed significant prospective associations between acute targeted rejection and nonspecified interpersonal stress during Period 1 and suicide ideation during Period 2, as well as relational victimization and noninterpersonal stress during Period 1 and suicide attempts during Period 2. However, in logistic regression analyses that adjusted for prior suicidality and depressive symptoms, relational victimization during Period 1 (but not targeted rejection, nonspecified interpersonal or noninterpersonal events) was associated with increased odds of suicide attempt during Period 2. Therefore, acute relational victimization exposure is associated with heightened risk for suicidal behaviors in female adolescents. Future studies should examine potential mediators and moderators of this association, and these stressors should be considered for inclusion in clinical screening tools.