The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis

In a randomized trial in Malawi of azithromycin versus placebo in over 2,000 pregnant women, Jim Neilson and colleagues show no benefit of azithromycin for a number of outcomes including preterm birth and prenatal death

A Didactic Model of Macromolecular Crowding Effects on Protein Folding

A didactic model is presented to illustrate how the effect of macromolecular crowding on protein folding and association is modeled using current analytical theory and discrete molecular dynamics. While analytical treatments of crowding may consider the effect as a potential of average force acting to compress a polypeptide chain into a compact state, the use of simulations enables the presence of crowding reagents to be treated explicitly. Using an analytically solvable toy model for protein folding, an approximate statistical thermodynamic method is directly compared to simulation in order to gauge the effectiveness of current analytical crowding descriptions. Both methodologies are in quantitative agreement under most conditions, indication that both current theory and simulation methods are capable of recapitulating aspects of protein folding even by utilizing a simplistic protein model

Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen (CEA) Gold 4 epitope and designed for radioimmunotherapy (RIT) of colorectal cancers

BACKGROUND: Human monoclonal antibodies (MAbs) are needed for colon cancer radioimmunotherapy (RIT) to allow for repeated injections. Carcinoembryonic antigen (CEA) being the reference antigen for immunotargeting of these tumors, we developed human anti-CEA MAbs. METHODS: XenoMouse(®)-G2 animals were immunized with CEA. Among all the antibodies produced, two of them, VG-IgG2κ and VG-IgM, were selected for characterization in vitro in comparison with the human-mouse chimeric anti-CEA MAb X4 using flow cytometry, surface plasmon resonance, and binding to radiolabeled soluble CEA and in vivo in human colon carcinoma LS174T bearing nude mice. RESULTS: Flow cytometry analysis demonstrated binding of MAbs on CEA-expressing cells without any binding on NCA-expressing human granulocytes. In a competitive binding assay using five reference MAbs, directed against the five Gold CEA epitopes, VG-IgG2κ and VG-IgM were shown to be directed against the Gold 4 epitope. The affinities of purified VG-IgG2κ and VG-IgM were determined to be 0.19 ± 0.06 × 10(8 )M(-1 )and 1.30 ± 0.06 × 10(8 )M(-1), respectively, as compared with 0.61 ± 0.05 × 10(8 )M(-1 )for the reference MAb X4. In a soluble phase assay, the binding capacities of VG-IgG2κ and VG-IgM to soluble CEA were clearly lower than that of the control chimeric MAb X4. A human MAb concentration of about 10(-7 )M was needed to precipitate approximatively 1 ng (125)I-rhCEA as compared with 10(-9 )M for MAb X4, suggesting a preferential binding of the human MAbs to solid phase CEA. In vivo, 24 h post-injection, (125)I-VG-IgG2κ demonstrated a high tumor uptake (25.4 ± 7.3%ID/g), close to that of (131)I-X4 (21.7 ± 7.2%ID/g). At 72 h post-injection, (125)I-VG-IgG2κ was still concentrated in the tumor (28.4 ± 11.0%ID/g) whereas the tumor concentration of (131)I-X4 was significantly reduced (12.5 ± 4.8%ID/g). At no time after injection was there any accumulation of the radiolabeled MAbs in normal tissues. A pertinent analysis of VG-IgM biodistribution was not possible in this mouse model in which IgM displays a very short half-life due to poly-Ig receptor expression in the liver. CONCLUSION: Our human anti-CEA IgG2κ is a promising candidate for radioimmunotherapy in intact form, as F(ab')(2 )fragments, or as a bispecific antibody

Functional outcome following excision of a tumour and reconstruction of the distal radius

We retrospectively studied the functional and oncological results of 15 patients after reconstruction of the distal radius with osteoarticular allograft or non-vascularised fibular graft following wide excision of an aggressive benign or malignant tumour. Eight patients underwent osteoarticular allograft and seven patients had a non-vascularised autogenous fibular graft reconstruction. The average time for incorporation of the graft was 6 and 5 months in each reconstruction respectively. There was no tumour recurrence after follow up over 41.5–95.5 (average 60.5) months. All patients had good and excellent functional results. Three patients in the group reconstructed with osteoarticular allograft had plate loosening and graft fractures which were successfully treated subsequently

Autonomic changes in young smokers: acute effects of inspiratory exercise

One of the most important consequences of smoking is the development of cardiovascular diseases. However, little is known about the early consequences of smoking and the acute effects of a single inspiratory muscle exercise session (IME). We evaluated the acute effects of an IME on cardiac parameters of young smokers.Twelve nonsmokers (C) and fifteen smokers [S; 2.08 (1.0-3.2) pack-years] underwent an acute IME. We evaluated blood pressure (BP) and lactate, and we recorded RR interval for posterior analysis of heart rate variability (HRV), before and after IME.At baseline, systolic BP and HRV parameters in time and frequency domains were changed in S group in comparison with the C. Following IME, S group reduced systolic BP (-8 %), low frequency band (LF) (-21.4 %), LF/high frequency (HF) (-57 %), as well as increased RR variance (+105 %) and HF band.Our findings indicate that a single session of inspiratory muscle exercise was able to both reduce systolic BP and improve parasympathetic and sympathetic modulations in young smokers. the results of the current study highlight the importance of furthering research on this area to better elucidate the acute and chronic effects of inspiratory muscle training on early cardiovascular and pulmonary changes of cigarette smoking.Univ Sao Judas Tadeu, Human Movement Lab, BR-03166000 São Paulo, BrazilUniv São Paulo, Sch Med, Heart Inst InCor, Hypertens Unit, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilNove de Julho Univ, Translat Physiol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc