Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by mutation.

Introduction: Increasing evidence implicates proteostatic dysfunction as an early event in the development of frontotemporal dementia (FTD). This study aimed to explore potential cerebrospinal fluid (CSF) biomarkers associated with the proteolytic systems in genetic FTD caused by mutation.

Methods: Combining solid-phase extraction and parallel reaction monitoring mass spectrometry, a panel of 47 peptides derived from 20 proteins was analyzed in CSF from 31 members of the Danish -FTD family.

Serum Neurofilament Light in Patients with Frontotemporal Dementia Caused by CHMP2B Mutation.

Introduction: The potential of neurofilament light (NfL) as a blood-based biomarker is currently being investigated in autosomal dominant neurodegenerative disease. This study explores the clinical utility of serum-NfL in frontotemporal dementia due to CHMP2B mutation (FTD-3).

Methods: This cross-sectional study included serum and CSF data from 38 members of the Danish FTD-3 family: 12 affected CHMP2B mutation carriers, 10 presymptomatic carriers, and 16 noncarriers.

Peripheral neuropathy in hereditary spastic paraplegia caused by REEP1 variants.

SPG31 is a hereditary spastic paraplegia (HSP) caused by pathogenic variants in the REEP1 gene. The phenotype (SPG31) has occasionally been described with peripheral nervous system involvement, in additional to the gradually progressing lower limb spasticity that characterizes HSP. The objective of this study was to characterize patients with pathogenic REEP1 variants and neurophysiologically assess the extent of peripheral nerve involvement in this patient group.

Concentrations of Intact Insulin Concurs With FDA and EMA Standards When Measured by HPLC in Different Parts of the Distribution Cold Chain.

Background: The article by Carter and Heinemann raised serious concerns about the concentrations of insulin in vials being sold in US pharmacies. To study the claims made in the manuscript, we reviewed Novo Nordisk data on insulin concentration.

Methods: Insulin concentrations within vials from three different sources along the distribution chain were evaluated utilizing currently accepted US Pharmacopeia methodology: (1) insulin content and stability based on production batches covering 7 years of insulin production, (2) insulin content in samples returned to Novo Nordisk over the last three years in the United States, and (3) data from eight years of independent EMA testing.

Biomarkers in Recurrent Grade III Glioma Patients Treated with Bevacizumab and Irinotecan.

Predictive biomarkers and prognostic models are required to identify recurrent grade III glioma patients who benefit from existing treatment. In this study of 62 recurrent grade III glioma patients, a range of clinical and paraclinical factors are tested for association with progression-free survival, overall survival, and response to bevacizumab and irinotecan therapy. Significant factors from univariate screening are included in multivariate analysis.

Early Visible Improvements during K101-03 Treatment: An Open-Label Multicenter Clinical Investigation in Patients with Onychomycosis and/or Nail Psoriasis.

Introduction: Onychomycosis and nail psoriasis can be embarrassing to patients, so improving the appearance of affected nails should be one of the key short-term goals of treatment.

Methods: An 8-week open-label multicenter study was conducted to assess whether K101-03, a marketed topical treatment containing propylene glycol, glycerol, urea, and lactic acid, could produce rapid cosmetic improvements in affected nails. Adult patients with a big toenail or thumbnail (the "target" nail) affected by onychomycosis (n = 72) or psoriasis (n = 34) or both (n = 1) applied K101-03 to their affected nails once a day for 8 weeks.

Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients.

Background: Bevacizumab combined with chemotherapy produces clinical durable response in 25-30% of recurrent glioblastoma patients. This group of patients has shown improved survival and quality of life. The aim of this study was to investigate changes in gene expression associated with response and resistance to bevacizumab combination therapy.

Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients.

Background: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers for bevacizumab response in recurrent glioblastoma patients.

Methods: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable.

Development and validation of a prognostic model for recurrent glioblastoma patients treated with bevacizumab and irinotecan.

Background: Predictive markers and prognostic models are required in order to individualize treatment of recurrent glioblastoma (GBM) patients. Here, we sought to identify clinical factors able to predict response and survival in recurrent GBM patients treated with bevacizumab (BEV) and irinotecan.

Material And Methods: A total of 219 recurrent GBM patients treated with BEV plus irinotecan according to a previously published treatment protocol were included in the initial population.

Bactericidal effect of colistin on planktonic Pseudomonas aeruginosa is independent of hydroxyl radical formation.

The bactericidal effect of several major types of antibiotics has recently been demonstrated to be dependent on the formation of toxic amounts of hydroxyl radicals (OH·) resulting from oxidative stress in metabolically active cells. Since killing by the antimicrobial peptide colistin does not require bacterial metabolic activity, we tested whether the bactericidal effect of colistin depends on the formation of OH·. In Pseudomonas aeruginosa cultures, OH-mediated killing by ciprofloxacin was demonstrated by decreased bacterial survival and induction of 3'-(p-hydroxyphenyl) fluorescein (HPF) fluorescence.

Clinical effectiveness of biphasic insulin aspart 30:70 versus biphasic human insulin 30 in UK general clinical practice: a retrospective database study.

Background: Premixed, or biphasic, insulins containing varying proportions of rapid- and intermediate-acting insulin components have been developed to limit the number of daily injections for patients who require both prandial and basal insulin injections.

Objectives: This study was conducted to determine whether there were differences in glycosylated hemoglobin (HbA(1c)), weight change, hypoglycemia occurrence, and treatment discontinuation between patients treated with biphasic insulin aspart 30 (BIAsp-30) or biphasic human insulin 30 (BHI-30) in UK general practice.

Methods: Data were from >350 general practices from the United Kingdom.

Source and kinetics of interleukin-6 in humans during exercise demonstrated by a minimally invasive model.

The objective of this study was to use a novel and non-invasive model to explore whether: (1) exercise-induced increases in systemic levels of interleukin-6 (IL-6) and other cytokines can be ascribed to local production in working muscle; and (2) how acute release of retained blood from an exercised limb impacts on metabolites in the systemic circulation. On two experimental days, at least 3 weeks apart, six healthy moderately trained male subjects performed one-legged knee-extensor exercise for 2 h at 60% of their maximal workload. On one occasion venous outflow from the exercised leg was inhibited for 18 min by inflating a cuff around the thigh as proximally as possible immediately following exercise.

Cytokine response to eccentric exercise in young and elderly humans.

To examine the plasma interleukin (IL)-6 response in elderly (E) and young (Y) humans, 10 E and 10 Y subjects completed 60 min of eccentric lower limb exercise at the same relative oxygen uptake. Plasma IL-6 was measured before, immediately after, and 5 days into recovery from exercise, as were the biochemical markers of muscle damage, creatine kinase (CK), and myoglobin. In both groups, IL-6 increased (P < 0.

Prolonged exercise, lymphocyte apoptosis and F2-isoprostanes.

Exercise induces a post-exercise decline in the number of circulating lymphocytes. The aim of the present study was to investigate whether strenuous exercise induces lymphocyte apoptosis and generation of reactive oxygen species. Eleven healthy male subjects exercised for 2.