Assessing the effect of introducing a new method into family planning programs in India, Peru, and Rwanda

ABSTRACT: BACKGROUND: Introducing a new method into family planning programs requires careful attention to ensure it meets an actual need and has a positive effect on program goals. The Standard Days Method(R) is a fertility awareness-based method of family planning that is being introduced into family planning programs in countries around the world. It is different from other methods offered by programs, and may bring new couples into family planning, and increase contraceptive prevalence. The study assesses the effect on contraceptive use and prevalence of Introducing Standard Days Method into existing family planning services in whole regions of India, Peru, and Rwanda. METHODS: In collaboration with the Ministry of Health, health providers were given a contraceptive update on all methods, then trained in counseling on Standard Days Method. Efforts were made to promote demand in the context of informed choice. Routine monthly service statistics in control and intervention areas were used to assess the effect of Standard Days Method introduction at the clinic level; baseline and endline household-based surveys were undertaken to obtain results at the community level (n > 3400 women at endline). RESULTS: Demand for the method is evident in countries with different levels of contraceptive prevalence. The method attracts couples new to family planning, and introducing it into services may increase overall contraceptive prevalence. CONCLUSIONS: Introducing Standard Days Method into existing family planning has the potential of benefiting men and women in diverse settings and populations. This study illustrates the critical role of evidence in scaling up a health innovation.     

Adenosine bronchial provocation with computerized wheeze detection in young infants with prolonged cough: correlation with long-term follow-up

BACKGROUND: Chronic cough in babies is often associated with bronchial hyperreactivity (BHR). The objective documentation of BHR in babies is difficult, and acoustic methods have been described (provocative concentration of a substance causing wheeze) for conducting bronchial provocation tests (BPTs). We conducted a study to evaluate automatic computerized wheeze detection (CWD) in determining BHR in young infants with prolonged cough, and its correlation with the subsequent development of wheezing. METHODS: Infants aged < 24 months with prolonged cough (ie, > 2 months) underwent acoustic BPTs with the response determined by CWD and auscultation by a physician. Telephone interviews with parents were conducted after 1 month and yearly for the next 3 years. RESULTS: A total of 28 infants who were 4 to 24 months old with prolonged cough were included in the study. Twenty of these infants (71.4%) had BHR as determined by a positive acoustic BPT result. In 11 of these 20 tests, the CWD occurred earlier, and in 9 tests it occurred at the same step as auscultation by a physician. Rhonchi or whistles often preceded wheezes. Seventeen of the 20 patients with BHR completed 3 years of follow-up. Of these, 14 had recurrent episodes of wheezing and shortness of breath, and 3 were well. Six of the eight adenosine-negative patients completed 3 years of follow-up and had no symptoms of BHR. CONCLUSIONS: Acoustic BPT is a technically feasible test for the detection of BHR in young infants. CWD provides an earlier detection of wheeze than stethoscope auscultation. In our group of infants, a positive acoustic BPT result had high correlation with symptoms compatible with BHR over the next 3 years.     

Respiratory virus infections in transplant recipients after reduced-intensity conditioning with Campath-1H: high incidence but low mortality

Respiratory virus infections can cause serious morbidity and mortality after conventional allogeneic stem cell transplantation. However, the incidence and outcome of these infections after reduced intensity conditioning has not been reported. Between 1997 and 2001, 35 episodes of respiratory virus infections were noted in 25 of 83 transplant recipients conditioned with fludarabine, melphalan and Campath-1H, and 80% of them received early antiviral therapy. Parainfluenza virus (PIV) 3 was the commonest isolate (45.7%) followed by respiratory syncytial virus (37%). Patients with myeloma were more susceptible to these infections [odds ratio (OR) 4.1, P = 0.01] which were often recurrent in patients with severe acute or chronic graft-versus-host disease (GVHD) (OR 10.6, P = 0.03). Infection within the first 100 d (OR 5.0, P = 0.05) and PIV 3 (OR 9.2, P = 0.01) isolation were risk factors for developing lower respiratory infection. Although more than half of the episodes progressed to lower respiratory infection, the mortality was only 8%. This could have been due to early initiation of antiviral therapy, but the attenuation of pulmonary damage due to the reduced-intensity conditioning, low incidence of GVHD and, paradoxically, the low CD4+ T-cell subset in this setting might also have been contributory factors.     

Genetic characterization of HA gene of low pathogenic H9N2 influenza viruses isolated in Israel during 2006–2012 periods

H9N2 influenza viruses are isolated in Israel since 2000 and became endemic. From November 2006 to the beginning of 2012, many H9N2 viruses were identified, all belonged to the Asian G1-like lineage represented by A/qu/Hong Kong/G1/97 (H9N2). In the present study, 66 isolates were selected for their hemagglutinin gene characterization. Most H9N2 isolates were distributed between two main groups, identified as the 4th and 5th introductions. The 5th introduction, was represented by a compact cluster containing viruses isolated in 2011–2012; the 4th introduction was subdivided into two subgroups, A and B, each containing at least two clusters, which can be identified as A-1, A-2, B-1, and B2, respectively. Genetic analysis of the deduced HA proteins of viruses, belonging to the 4th and 5th introductions, revealed amino acid variations in 79 out of 542 positions. All isolates had typical low pathogenicity motifs at the hemagglutinin (HA) cleavage site. Most viruses had leucine at position 216 in a receptor binding pocket that enables the virus to bind successfully with the cellular receptors intrinsic to mammals, including humans. It was shown that the differences between the HA proteins of viruses used for vaccine production and local field isolates increased in parallel with the duration and intensity of vaccine use, illustrating the genetic diversity of the H9N2 viruses in Israel.     

The docking protein FRS2α is a critical regulator of VEGF receptors signaling

Vascular endothelial growth factors (VEGFs) signal via their cognate receptor tyrosine kinases designated VEGFR1-3. We report that the docking protein fibroblast growth factor receptor substrate 2 (FRS2α) plays a critical role in cell signaling via these receptors. In vitro FRS2α regulates VEGF-A and VEGF-C–dependent activation of extracellular signal-regulated receptor kinase signaling and blood and lymphatic endothelial cells migration and proliferation. In vivo endothelial-specific deletion of FRS2α results in the profound impairment of postnatal vascular development and adult angiogenesis, lymphangiogenesis, and arteriogenesis. We conclude that FRS2α is a previously unidentified component of VEGF receptors signaling.Vascular endothelial growth factors (VEGFs) are key regulators of blood and lymphatic vessel development and homeostasis. The absence of VEGF-A during development results in a complete failure of blood vasculature formation (1), whereas VEGF-C knockout abolishes lymphangiogenesis (2). Both VEGF-A and VEGF-C play equally critical roles in postnatal formation and maintenance of various blood and lymphatic vessel beds (3–6). The two VEGFs signal via, respectively, the two receptor tyrosine kinases (RTK) VEGFR2 and VEGFR3 with the former primarily expressed in the arterial and venous vasculature and the latter in the lymphatic vasculature in adult tissues (7). The other VEGF receptor, VEGFR1, is thought to function largely as a “decoy” receptor in endothelial cells but can transmit signaling in mononuclear cells (7).All VEGF receptors share a number of structural similarities including an extracellular ligand binding domain, a single transmembrane region, and a cytoplasmic domain containing a tyrosine kinase domain with an insert region. Receptor activation requires ligand-induced dimerization that results in autophosphorylation of cytoplasmic tyrosines that serve as binding sites for various signaling proteins. In the case of VEGF-A receptor, VEGFR2 phosphorylation of Y¹⁰⁵⁴/Y¹⁰⁵⁹ is required for maximal VEGFR2 kinase activity that leads to phosphorylation of Y¹¹⁷⁵ (a phospholipase Cγ1 binding site also required for ERK activation) and Y⁹⁵¹ (a TSAd binding site leading to Src activation) among others (7). VEGF-C signals via VEGFR3 in a similar manner.In the course of studying fibroblast growth factor (FGF) signaling, we noticed that an endothelial knockdown or deletion of a scaffold protein FRS2α, known to be involved in FGF and neural growth factor (NGF) receptor signaling (8–10), also affects VEGF signaling. FRS2α is a docking protein that contains an N-terminal myristylation site, a PTB domain, and a large C-terminal tail that contains four binding sites for the SH2 domain of the adaptor protein Grb2 and two binding sites for the SH2 domain of the tyrosine phosphatase Shp2 (11). Tyrosine phosphorylation of FRS2α at these binding sites leads to activation of MAPK signaling (12).In this study, we found that FRS2α plays a central role in regulation of VEGF signaling in blood and lymphatic endothelial cells. Its deletion profoundly reduced VEGF signaling in vitro and in vivo and resulted in impairment of postnatal vascular development and adult angiogenesis, lymphangiogenesis, and arteriogenesis.