Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease

Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC₅₀s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI–EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.     

Quantifying the Effects of Aging on Morphological and Cellular Properties of Human Female Pelvic Floor Muscles

Annals of Biomedical Engineering - Age-related pelvic floor muscle (PFM) dysfunction is a critical defect in the progression to pelvic floor disorders (PFDs). Despite dramatic prevalence of PFDs in...     

Plasma concentration of atrial natriuretic peptide is related to the duration of atrial fibrillation in patients with advanced heart failure

BACKGROUND: Plasma concentration of atrial natriuretic peptide (ANP) is elevated in patients with atrial fibrillation (AF) and in patients with chronic heart failure (CHF).Aim. To assess ANP level in patients with permanent AF and advanced CHF. METHODS: The study group consisted of 41 patients (27 males, mean age 62+/-8 years) with AF of a mean duration of 8.8 months. Twenty six (63%) patients were in NYHA class II, and 15 (37%) - in NYHA class III or IV. All patients underwent clinical and echocardiographic evaluation as well as ANP plasma concentration assessment. Multiple regression analysis was used to identify factors which determine ANP plasma concentration. RESULTS: Mean ANP plasma concentration was 52.4+/-22.7 pg/ml in the whole study group; 38.6+/-10.8 pg/ml in NYHA class II patients and 74.9+/-18.7 pg/ml in NYHA class III-IV subjects (p<0.0001). Among echocardiographic parameters, patients with NYHA class III or IV had significantly lower left ventricular ejection fraction and greater left atrial volume than patients with NYHA class II (32% versus 56%, p<0.0001 and 101.0+/-23.8 cm(3) versus 83.4+/-16.1 cm(3), p<0.006, respectively). Multiple regression analysis revealed a significant negative correlation between AF duration and ANP level (p=0.0013) in a group of patients with NYHA class III or IV and identified AF duration as an independent predictor of ANP plasma concentration in this group of patients. CONCLUSIONS: ANP plasma concentration in patients with persistent AF and advanced CHF is determined by AF duration - the longer the AF duration the lower the ANP level.     

An update on red blood cell storage lesions,as gleaned through biochemistry and omics technologies

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high‐energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long‐stored RBCs and promote the rapid clearance of up to one‐fourth of long‐stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects.