Prevention of violence against women and girls: A cost-effectiveness study across 6 low- and middle-income countries

BackgroundViolence against women and girls (VAWG) is a human rights violation with social, economic, and health consequences for survivors, perpetrators, and society. Robust evidence on economic, social, and health impact, plus the cost of delivery of VAWG prevention, is critical to making the case for investment, particularly in low- and middle-income countries (LMICs) where health sector resources are highly constrained. We report on the costs and health impact of VAWG prevention in 6 countries.Methods and findingsWe conducted a trial-based cost-effectiveness analysis of VAWG prevention interventions using primary data from 5 randomised controlled trials (RCTs) in sub-Saharan Africa and 1 in South Asia. We evaluated 2 school-based interventions aimed at adolescents (11 to 14 years old) and 2 workshop-based (small group or one to one) interventions, 1 community-based intervention, and 1 combined small group and community-based programme all aimed at adult men and women (18+ years old). All interventions were delivered between 2015 and 2018 and were compared to a do-nothing scenario, except for one of the school-based interventions (government-mandated programme) and for the combined intervention (access to financial services in small groups). We computed the health burden from VAWG with disability-adjusted life year (DALY). We estimated per capita DALYs averted using statistical models that reflect each trial’s design and any baseline imbalances. We report cost-effectiveness as cost per DALY averted and characterise uncertainty in the estimates with probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEACs), which show the probability of cost-effectiveness at different thresholds. We report a subgroup analysis of the small group component of the combined intervention and no other subgroup analysis. We also report an impact inventory to illustrate interventions’ socioeconomic impact beyond health. We use a 3% discount rate for investment costs and a 1-year time horizon, assuming no effects post the intervention period. From a health sector perspective, the cost per DALY averted varies between US$222 (2018), for an established gender attitudes and harmful social norms change community-based intervention in Ghana, to US$17,548 (2018) for a livelihoods intervention in South Africa. Taking a societal perspective and including wider economic impact improves the cost-effectiveness of some interventions but reduces others. For example, interventions with positive economic impacts, often those with explicit economic goals, offset implementation costs and achieve more favourable cost-effectiveness ratios. Results are robust to sensitivity analyses. Our DALYs include a subset of the health consequences of VAWG exposure; we assume no mortality impact from any of the health consequences included in the DALYs calculations. In both cases, we may be underestimating overall health impact. We also do not report on participants’ health costs.ConclusionsWe demonstrate that investment in established community-based VAWG prevention interventions can improve population health in LMICs, even within highly constrained health budgets. However, several VAWG prevention interventions require further modification to achieve affordability and cost-effectiveness at scale. Broadening the range of social, health, and economic outcomes captured in future cost-effectiveness assessments remains critical to justifying the investment urgently required to prevent VAWG globally.

In a cost-effectiveness study, Dr. Giulia Ferrari and colleagues examine the costs and health impact of prevention of violence against women and girls in six low- and middle-income countries.     

Conformational and ion-binding properties of cyclolinopeptide A isolated from linseed

The conformation of the cyclic nonaPePtide from linseed, cyclolinoPePtide A in methanol and in acetonitrile has been elucidated by one-and two-dimensional nuclear magnetic resonance. The molecule is folded in a β-turn conformation. CyclolinoPePtide A interacts and weakly comPlexes with Tb³⁺ (a Ca²⁺ mimic ion) with the metal ion Positioned Proximally to the Phe residue, but with no substantial structural alteration uPon metal binding. CyclolinoPePtide A is also seen to aid the translocation of Pr³⁺ (another Ca²⁺ mimic) across unilamellar liPosomes. However, cyclolinoPePtide A does not Phase transfer or act as an ionoPhore of calcium ion myself. ExPeriments using lanthanide ions thus do not necessarily indicate any ionoPhoretic ability of the comPlexone towards calcium ions.     

The role of the omega subunit of RNA polymerase in expression of the relA gene in Escherichia coli

The rpoZ gene for the omega subunit of Escherichia coli RNA polymerase constitutes single operon with the spoT gene, which is responsible for the maintenance of stringent response under nutrient starvation conditions. To identify the physiological role of the omega subunit, we compared the gene expression profile of wild-type Escherichia coli with that of an rpoZ deleted strain by microarray analysis using an E. coli DNA chip. Here we report on a set of genes which show changes in expression profile following the removal of rpoZ. We have seen that relA, which is responsible for the synthesis of the stringent factor ppGpp and many ribosomal proteins, exhibited noticeable changes in mRNA levels and were therefore further analyzed for their expression using a GFP/RFP two-fluorescent protein promoter assay vector. In the absence of rpoZ, the promoter for the relA gene was severely impaired, but the promoters from the ribosomal protein genes were not affected as much. Taking these results together we propose that the omega subunit is involved in regulation of the relA gene, but induction of the stringently controlled genes in the absence of rpoZ is, at least in part, attributable to a decrease in ppGpp level.     

Functional complementation between mutations at two distant positions in Escherichia coli RNA polymerase as revealed by second-site suppression

Subunit-subunit interactions are critical for the assembly of the core of Escherichia coli RNA polymerase. The mutant alpha-subunit C131A is unable to complement the temperature-sensitive alpha-R45C mutant strain, which is defective for binding of the beta-subunit. In vitro reconstitution experiments, however, indicate that the alpha-C131A variant is able to form the intermediate alpha2beta, but is defective in contacting the beta'-subunit. We used this alpha-C131A mutant to isolate a suppressor mutation in the beta'-subunit. Genetic and biochemical characterization of the beta' suppressor indicates the allele-specific nature of its effect. Sequence analysis of the suppressor revealed a single substitution of Gly at position 333, an evolutionarily conserved position in the conserved region C of the beta'-subunit, by Asp. However, the crystal structure of the bacterial RNA polymerase indicates that the primary mutation (alpha-C131A) and its suppressor lie far apart. Thus, we propose that long-range interactions, as in this case, may play an important role in the functional assembly of E. coli RNA polymerase.     

LIBS Based Screening of Glycemic Elements of Ficus religiosa

The effectiveness of various trace element concentrations in medicinal plants in the cure of various diseases can be determined by their quantitative estimation. Elemental concentrations of aqueous extract of F. religiosa leaves were measured by Laser-induced breakdown spectroscopy (LIBS). LIBS is a very powerful and efficient analytical tool for determining elemental constitution. The present study deals with the LIBS-based validation of elements responsible for the glycemic potential of aqueous extract of F. religiosa leaves in streptozotocin-induced diabetic models. The significant decrease in blood glucose level and marked improvement in glucose tolerance test of diabetic models is correlated to the concentration of elements present in the extract as revealed by LIBS spectra. Elements such as Mg and Ca have been observed in the LIBS spectra of F. religiosa.     

Effect of extracellular pH and DNFB treatment on the mechanical performance of frog skeletal muscle

isometric tension and maximum velocity of shortening of frog sartorious and biceps muscles were measured at varying pH and compared with the values obtained for muscles treated with DNFB. Both To and Vmax exhibited increase with increase in pH above neutral pH upto pH 9, and decreased as the pH was decreased up to 5. Muscle treated with DNFB at pH 7 showed about 30% decrement but these too improved at pH 9 to almost 105% and 130% respectively compared to untreated muscle at pH 7. Using the number of short duration tetanic contractions, which reduce To and Vmax by half, as an index for the onset of fatigue, high pH was found to have a positive effect in both normal and DNFB-treated muscle. Thus, the crucial factor for onset of fatigue is not a fall in ATP level but acidification and treatment with high pH Ringer's solution partially annuls the effect of acidosis, arising either naturally or from DNFB treatment. One additional role of creatine kinase activity to that of ATP regeneration is suggested to be the maintenance of neutral pH in the sarcoplasm.     

Serum proteomics of lung adenocarcinomas induced by targeted overexpression of c-raf in alveolar epithelium identifies candidate biomarkers

We previously reported a proteome map of lung adenocarcinomas in serine-threonine kinase of the Raf family (c-raf) transgenic mice. We now extend our initial studies to serum proteins at early stage (1 month) and advanced stages of tumorigenesis (12 months). Notably, serum proteins from wild-type and tumor bearing mice were extracted with a lysis buffer containing 5 mol/L urea, 2 mol/L thiourea, 40 mmol/L Tris, 4% CHAPS, 100 mmol/L DTT, 0.5% BioLyte 3-10, separated by 2-DE and studied by image analysis. On average 400 protein spots per gel were excised and analyzed by MALDI-TOF MS. We identified 45 common and 5 uniquely expressed proteins in wild-type and tumor bearing mice. Apart from uniquely identified proteins we observed for n = 9 proteins differential expression when wild-type and tumor bearing mice were compared. This included serpins and other protease inhibitors, lipocalins, transthyretins, globins, and Igs. Notably, we demonstrate significant regulation of alpha-1-antitrypsin, alpha-2-macroglobulin, hemoglobin subunit alpha, vitamin D-binding protein, major urinary proteins, and transthyretin (up to eight-fold) in serum of lung tumor bearing mice. Disease association of these proteins in human malignancies has been reported. Thus, an identification of regulated serum proteins in this lung cancer disease model provides excellent opportunities for the search of novel biomarkers.     

Correlation between NS5A Dimerization and Hepatitis C Virus Replication

Hepatitis C virus (HCV) is the main agent of acute and chronic liver diseases leading to cirrhosis and hepatocellular carcinoma. The current standard therapy has limited efficacy and serious side effects. Thus, the development of alternate therapies is of tremendous importance. HCV NS5A (nonstructural 5A protein) is a pleiotropic protein with key roles in HCV replication and cellular signaling pathways. Here we demonstrate that NS5A dimerization occurs through Domain I (amino acids 1-240). This interaction is not mediated by nucleic acids because benzonase, RNase, and DNase treatments do not prevent NS5A-NS5A interactions. Importantly, DTT abrogates NS5A-NS5A interactions but does not affect NS5A-cyclophilin A interactions. Other reducing agents such as tris(2-carboxyethyl)phosphine and 2-mercaptoethanol also abrogate NS5A-NS5A interactions, implying that disulfide bridges may play a role in this interaction. Cyclophilin inhibitors, cyclosporine A, and alisporivir and NS5A inhibitor BMS-790052 do not block NS5A dimerization, suggesting that their antiviral effects do not involve the disruption of NS5A-NS5A interactions. Four cysteines, Cys-39, Cys-57, Cys-59, and Cys-80, are critical for dimerization. Interestingly, the four cysteines have been proposed to form a zinc-binding motif. Supporting this notion, NS5A dimerization is greatly facilitated by Zn(2+) but not by Mg(2+) or Mn(2+). Importantly, the four cysteines are vital not only for viral replication but also critical for NS5A binding to RNA, revealing a correlation between NS5A dimerization, RNA binding, and HCV replication. Altogether our data suggest that NS5A-NS5A dimerization and/or multimerization could represent a novel target for the development of HCV therapies.