Targeting melanoma by small molecules: challenges ahead

Significant progress has been made in targeting melanoma using small molecule inhibitors, but challenges remain. Here we describe the history of screening approaches in melanoma and their limitations. We propose several approaches to refine our screening models to enhance the discovery process. It is hoped that this discussion will stimulate further improvements in our development of small molecules inhibitors for treatment of melanoma patients.     

Meta‐analysis of the association between body mass index and health‐related quality of life among adults,assessed by the SF‐36

Objective:

Obesity is associated with impaired overall health‐related quality of life but individual studies suggest the relationship may differ for mental and physical quality of life. A systematic review using Medline, Embase, PsycINFO and ISI Web of Knowledge, and random effects meta‐analysis was undertaken.

Design and Methods:

Studies were included in the meta‐analysis if they were conducted on adults (defined as age >16 years), reported an overall physical and mental component score of the SF‐36, and, or both. Heterogeneity was assessed using I² statistics and publication and small study biases using funnel plots and Egger's test. Between‐study heterogeneity was explored using meta‐regression.

Results:

Eight eligible studies provided 42 estimates of effect size, based on 43,086 study participants. Adults with higher than normal body mass index had significantly reduced physical quality of life with a clear dose‐response relationship across all categories. Among class III obese adults, the score was reduced by 9.72 points (95% Confidence Interval 7.24, 12.20, P < 0.001). Mental quality of life was also significantly reduced among class III obese (?1.75, 95% confidence interval ?3.33, ?0.16, P = 0.031), but was not significantly different among obese (class I and class II) individuals, and was significantly increased among overweight adults (0.42, 95% confidence interval 0.17, 0.67, P = 0.001), compared to normal weight individuals. Heterogeneity was high in some categories, but there was no significant publication or small study bias.

Conclusions:

Different patterns were observed for physical and mental HRQoL, but both were impaired in obese individuals. This meta‐analysis provides further evidence on the impact of obesity on both aspects of health‐related quality of life.

     

Freshwater salinization syndrome: from emerging global problem to managing risks

Freshwater salinization is an emerging global problem impacting safe drinking water, ecosystem health and biodiversity, infrastructure corrosion, and food production. Freshwater salinization originates from diverse anthropogenic and geologic sources including road salts, human-accelerated weathering, sewage, urban construction, fertilizer, mine drainage, resource extraction, water softeners, saltwater intrusion, and evaporative concentration of ions due to hydrologic alterations and climate change. The complex interrelationships between salt ions and chemical, biological, and geologic parameters and consequences on the natural, social, and built environment are called Freshwater Salinization Syndrome (FSS). Here, we provide a comprehensive overview of salinization issues (past, present, and future), and we investigate drivers and solutions. We analyze the expanding global magnitude and scope of FSS including its discovery in humid regions, connections to human-accelerated weathering and mobilization of ‘chemical cocktails.’ We also present data illustrating: (1) increasing trends in salt ion concentrations in some of the world’s major freshwaters, including critical drinking water supplies; (2) decreasing trends in nutrient concentrations in rivers due to regulations but increasing trends in salinization, which have been due to lack of adequate management and regulations; (3) regional trends in atmospheric deposition of salt ions and storage of salt ions in soils and groundwater, and (4) applications of specific conductance as a proxy for tracking sources and concentrations of groups of elements in freshwaters. We prioritize FSS research needs related to better understanding: (1) effects of saltwater intrusion on ecosystem processes, (2) potential health risks from groundwater contamination of home wells, (3) potential risks to clean and safe drinking water sources, (4) economic and safety impacts of infrastructure corrosion, (5) alteration of biodiversity and ecosystem functions, and (6) application of high-frequency sensors in state-of-the art monitoring and management. We evaluate management solutions using a watershed approach spanning air, land, and water to explore variations in sources, fate and transport of different salt ions (e.g. monitoring of atmospheric deposition of ions, stormwater management, groundwater remediation, and managing road runoff). We also identify tradeoffs in management approaches such as unanticipated retention and release of chemical cocktails from urban stormwater management best management practices (BMPs) and unintended consequences of alternative deicers on water quality. Overall, we show that FSS has direct and indirect effects on mobilization of diverse chemical cocktails of ions, metals, nutrients, organics, and radionuclides in freshwaters with mounting impacts. Our comprehensive review suggests what could happen if FSS were not managed into the future and evaluates strategies for reducing increasing risks to clean and safe drinking water, human health, costly infrastructure, biodiversity, and critical ecosystem services.

     

Characterization, Genetic Diversity, and Evolutionary Link of Cucumber mosaic virus Strain New Delhi from India

The genome of Cucumber mosaic virus New Delhi strain (CMV-ND) from India, obtained from tomato, was completely sequenced and compared with full genome sequences of 14 known CMV strains from subgroups I and II, for their genetic diversity. Sequence analysis suggests CMV-ND shares maximum sequence identity at the nucleotide level with a CMV strain from Taiwan. Among all 15 strains of CMV, the encoded protein 2b is least conserved, whereas the coat protein (CP) is most conserved. Sequence identity values and phylogram results indicate that CMV-ND belongs to subgroup I. Based on the recombination detection program result, it appears that CMV is prone to recombination, and different RNA components of CMV-ND have evolved differently. Recombinational analysis of all 15 CMV strains detected maximum recombination breakpoints in RNA2; CP showed the least recombination sites.     

Effect of codon-optimized E. coli signal peptides on recombinant Bacillus stearothermophilus maltogenic amylase periplasmic localization,yield and activity

Recombinant proteins can be targeted to the Escherichia coli periplasm by fusing them to signal peptides. The popular pET vectors facilitate fusion of target proteins to the PelB signal. A systematic comparison of the PelB signal with native E. coli signal peptides for recombinant protein expression and periplasmic localization is not reported. We chose the Bacillus stearothermophilus maltogenic amylase (MA), an industrial enzyme widely used in the baking and brewing industry, as a model protein and analyzed the competence of seven, codon-optimized, E. coli signal sequences to translocate MA to the E. coli periplasm compared to PelB. MA fusions to three of the signals facilitated enhanced periplasmic localization of MA compared to the PelB fusion. Interestingly, these three fusions showed greatly improved MA yields and between 18- and 50-fold improved amylase activities compared to the PelB fusion. Previously, non-optimal codon usage in native E. coli signal peptide sequences has been reported to be important for protein stability and activity. Our results suggest that E. coli signal peptides with optimal codon usage could also be beneficial for heterologous protein secretion to the periplasm. Moreover, such fusions could even enhance activity rather than diminish it. This effect, to our knowledge has not been previously documented. In addition, the seven vector platform reported here could also be used as a screen to identify the best signal peptide partner for other recombinant targets of interest.     

Impact of a Participatory Intervention with Women’s Groups on Psychological Distress among Mothers in Rural Bangladesh: Secondary Analysis of a Cluster-Randomised Controlled Trial

Background

Perinatal common mental disorders (PCMDs) are a major cause of disability among women and disproportionately affect lower income countries. Interventions to address PCMDs are urgently needed in these settings, and group-based and peer-led approaches are potential strategies to increase access to mental health interventions. Participatory women’s health groups led by local women previously reduced postpartum psychological distress in eastern India. We assessed the effect of a similar intervention on postpartum psychological distress in rural Bangladesh.

Method

We conducted a secondary analysis of data from a cluster-randomised controlled trial with 18 clusters and an estimated population of 532,996. Nine clusters received an intervention comprising monthly meetings during which women’s groups worked through a participatory learning and action cycle to develop strategies for improving women’s and children’s health. There was one group for every 309 individuals in the population, 810 groups in total. Mothers in nine control clusters had access to usual perinatal care. Postpartum psychological distress was measured with the 20-item Self Reporting Questionnaire (SRQ-20) between six and 52 weeks after delivery, during the months of January to April, in 2010 and 2011.

Results

We analysed outcomes for 6275 mothers. Although the cluster mean SRQ-20 score was lower in the intervention arm (mean 5.2, standard deviation 1.8) compared to control (5.3, 1.2), the difference was not significant (β 1.44, 95% CI 0.28, 3.08).

Conclusions

Despite promising results in India, participatory women’s groups focused on women’s and children’s health had no significant effect on postpartum psychological distress in rural Bangladesh.     

Numerical Solution to Generalized Burgers'-Fisher Equation Using Exp-Function Method Hybridized with Heuristic Computation

In this paper, a new heuristic scheme for the approximate solution of the generalized Burgers''-Fisher equation is proposed. The scheme is based on the hybridization of Exp-function method with nature inspired algorithm. The given nonlinear partial differential equation (NPDE) through substitution is converted into a nonlinear ordinary differential equation (NODE). The travelling wave solution is approximated by the Exp-function method with unknown parameters. The unknown parameters are estimated by transforming the NODE into an equivalent global error minimization problem by using a fitness function. The popular genetic algorithm (GA) is used to solve the minimization problem, and to achieve the unknown parameters. The proposed scheme is successfully implemented to solve the generalized Burgers''-Fisher equation. The comparison of numerical results with the exact solutions, and the solutions obtained using some traditional methods, including adomian decomposition method (ADM), homotopy perturbation method (HPM), and optimal homotopy asymptotic method (OHAM), show that the suggested scheme is fairly accurate and viable for solving such problems.     

Developing the Evidence Base to Inform Best Practice: A Scoping Study of Breast and Cervical Cancer Reviews in Low- and Middle-Income Countries

Background

Breast and cervical cancers have emerged as major global health challenges and disproportionately lead to excess morbidity and mortality in low- and middle-income countries (LMICs) when compared to high-income countries. The objective of this paper was to highlight key findings, recommendations, and gaps in research and practice identified through a scoping study of recent reviews in breast and cervical cancer in LMICs.

Methods

We conducted a scoping study based on the six-stage framework of Arskey and O’Malley. We searched PubMed, Cochrane Reviews, and CINAHL with the following inclusion criteria: 1) published between 2005-February 2015, 2) focused on breast or cervical cancer 3) focused on LMIC, 4) review article, and 5) published in English.

Results

Through our systematic search, 63 out of the 94 identified cervical cancer reviews met our selection criteria and 36 of the 54 in breast cancer. Cervical cancer reviews were more likely to focus upon prevention and screening, while breast cancer reviews were more likely to focus upon treatment and survivorship. Few of the breast cancer reviews referenced research and data from LMICs themselves; cervical cancer reviews were more likely to do so. Most reviews did not include elements of the PRISMA checklist.

Conclusion

Overall, a limited evidence base supports breast and cervical cancer control in LMICs. Further breast and cervical cancer prevention and control studies are necessary in LMICs.     

Eggs Distribution Behaviour of Dubas Bug (Ommatissus Lybicus: Homoptera: Tropiduchidae) in Relation to Seasons and Some Physico- Morphic Characters of Date Palm Leaves

Dubas bug, Ommatissus lybicus, is a major pest of date palm in Panjgur Balochistan. Both the nymphs and adults suck the sap from fruit stalk, leaves and may cause about 50 % of economic losses. Chlorophyll contents and leaf thickness was measured by using SPAD-502 chlorophyll meter and vernier caliper respectively. Eggs distribution density was highly significant in different frond rows and within frond during spring (1^st) and summer (2^nd) generations. In both generations number of eggs per leaflet decreased towards the apex fronds rows and within frond number of eggs decreased towards the terminal leaflets. Eggs distribution had negative correlation with leaf thickness; chlorophyll contents (SPAD value) and frond row (bottom to top). Apparently shade affect the eggs laying behaviour of dubas bug.     

Molecular classification of Pakistani collared dove through DNA barcoding

Pakistan is bestowed by a diversified array of wild bird species including collared doves of which the taxonomy has been least studied and reported. DNA barcoding is a geno-taxonomic tool that has been used for characterization of bird species using mitochondrial cytochrome c oxidase I gene (COI). This study aimed to identify taxonomic order of Pakistani collared dove using DNA barcoding. Purposely herein, we present a phylogenetic analysis of Pakistani collared dove based on 650 base pairs of COI gene sequences. Analysis of phylogenetic tree revealed that Pakistani collared dove shared a common clade with Eurasian collared dove (Streptopelia decaocto) and African collared dove (Streptopelia roseogrisea) which indicated a super-species group in Streptopelia genus. This is the first report of molecular classification of Pakistani collared dove using DNA barcoding.