Assessment of Anthelmintic Efficacy of Mebendazole in School Children in Six Countries Where Soil-Transmitted Helminths Are Endemic

Background

Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained for similarly conducted trials of a single oral dose of albendazole (ALB; 400 mg).

Methodology

The efficacy of MEB, as assessed by FECR, was determined in six trials involving 5,830 school children in Brazil, Cambodia, Cameroon, Ethiopia, United Republic of Tanzania, and Vietnam. The efficacy of MEB was compared to that of ALB as previously assessed in 8,841 school children in India and all the above-mentioned study sites, using identical methodologies.

Principal Findings

The estimated FECR rate [95% confidence interval] of MEB was highest for A. lumbricoides (97.6% [95.8; 99.5]), followed by hookworm (79.6% [71.0; 88.3]). For T. trichiura, the estimated FECR rate was 63.1% [51.6; 74.6]. Compared to MEB, ALB was significantly more efficacious against hookworm (96.2% [91.1; 100], p<0.001) and only marginally, although significantly, better against A. lumbricoides infections (99.9% [99.0; 100], p = 0.012), but equally efficacious for T. trichiura infections (64.5% [44.4; 84.7], p = 0.906).

Conclusions/Significance

A minimum FECR rate of 95% for A. lumbricoides, 70% for hookworm, and 50% for T. trichiura is expected in MEB-dependent PC programs. Lower FECR results may indicate the development of potential drug resistance.     

Accumulation of cyclophilin A isoforms in conditioned medium of irradiated breast cancer cells

Secreted proteins play a key role in cell signaling and communication. We recently showed that ionizing radiations induced a delayed cell death of breast cancer cells, mediated by the death receptor pathways through the expression of soluble forms of "death ligands." Using the same cell model, the objective of our work was the identification of diffusible factors, secreted following cell irradiation, potentially involved in cell death signaling. Differential proteomic analysis of conditioned media using 2DE resulted in detection of numerous spots that were significantly modulated following cell irradiation. The corresponding proteins were identified using MALDI-TOF MS and LC-MS/MS approaches. Interestingly, five isoforms of cyclophilin A were observed as increased in conditioned medium of irradiated cells. These isoforms differed in isoelectric points and in accumulation levels. An increase of cyclophilin A secretion was confirmed by Western blotting of conditioned media of irradiated or radiosentive mammary cells. These isoforms displayed an interesting pattern of protein maturation and post-translational modifications, including an alternating removal of N-terminal methionine, associated with a combination of acetylations and methylations. The role of the protein is discussed in relation with its potential involvement in the mechanisms of intercells relationships and radiosensitivity.     

Designing connected marine reserves in the face of global warming

Marine reserves are widely used to protect species important for conservation and fisheries and to help maintain ecological processes that sustain their populations, including recruitment and dispersal. Achieving these goals requires well‐connected networks of marine reserves that maximize larval connectivity, thus allowing exchanges between populations and recolonization after local disturbances. However, global warming can disrupt connectivity by shortening potential dispersal pathways through changes in larval physiology. These changes can compromise the performance of marine reserve networks, thus requiring adjusting their design to account for ocean warming. To date, empirical approaches to marine prioritization have not considered larval connectivity as affected by global warming. Here, we develop a framework for designing marine reserve networks that integrates graph theory and changes in larval connectivity due to potential reductions in planktonic larval duration (PLD) associated with ocean warming, given current socioeconomic constraints. Using the Gulf of California as case study, we assess the benefits and costs of adjusting networks to account for connectivity, with and without ocean warming. We compare reserve networks designed to achieve representation of species and ecosystems with networks designed to also maximize connectivity under current and future ocean‐warming scenarios. Our results indicate that current larval connectivity could be reduced significantly under ocean warming because of shortened PLDs. Given the potential changes in connectivity, we show that our graph‐theoretical approach based on centrality (eigenvector and distance‐weighted fragmentation) of habitat patches can help design better‐connected marine reserve networks for the future with equivalent costs. We found that maintaining dispersal connectivity incidentally through representation‐only reserve design is unlikely, particularly in regions with strong asymmetric patterns of dispersal connectivity. Our results support previous studies suggesting that, given potential reductions in PLD due to ocean warming, future marine reserve networks would require more and/or larger reserves in closer proximity to maintain larval connectivity.     

Physiological Alterations and Heavy Metal Accumulation in the Lichen Pyxine cocoes (Sw.) Nyl. of Mandi District,Himachal Pradesh

Journal of Plant Growth Regulation - Pyxine cocoes&nbsp;(Sw.) Nyl., foliose lichen is widespread in the region and grows luxuriantly on the various substrata. For the elemental concentration...     

Phosphorylation dynamics of membrane proteins from Arabidopsis roots submitted to salt stress

An excess of NaCl in the soil is detrimental for plant growth. It interferes with mineral nutrition and water uptake and leads to accumulation of toxic ions in the plant. Understanding the response of roots to NaCl stress may facilitate the development of crops with increased tolerance to this and other stresses. Since controls achieved at the posttranslational level are of critical importance for regulating protein function, the present work used a robust label‐free quantitative proteomic methodology to quantify phosphorylation events that affect root membrane proteins in Arabidopsis, in response to short‐term (up to 2 h) NaCl treatments. This work identified 302 proteotypic phosphopeptides including 77 novel phosphorylated sites. NaCl treatment significantly altered the abundance of 74 phosphopeptides, giving novel insights into the regulation of major classes of membrane proteins, including ATPases, sodium transporters, and aquaporins. The data provide a unique access to phosphorylation reprogramming of ionic equilibrium in plant cells under NaCl stress. The use of predictive bioinformatic tools for kinase motifs suggested that root membrane proteins are substrates of cAMP‐dependent protein kinase, cGMP‐dependent protein kinase, and protein kinase C families, also called AGC kinases, arguing for an important role of lipid signaling in abiotic stress responses. It also pointed to cross‐talks between protein kinase families during NaCl stress.     

Patterns and determinants of elephant attacks on humans in Nepal

Attacks on humans by Asian elephant (Elephas maximus) is an extreme form of human–elephant conflict. It is a serious issue in southern lowland Nepal where elephant‐related human fatalities are higher than other wildlife. Detailed understanding of elephant attacks on humans in Nepal is still lacking, hindering to devising appropriate strategies for human–elephant conflict mitigation. This study documented spatiotemporal pattern of elephant attacks on humans, factors associated with the attacks, and human/elephant behavior contributing to deaths of victims when attacked. We compiled all the documented incidences of elephant attacks on humans in Nepal for last 20 years across Terai and Chure region of Nepal. We also visited and interviewed 412 victim families (274 fatalities and 138 injuries) on elephant attacks. Majority of the victims were males (87.86%) and had low level of education. One fourth of the elephant attacks occurred while chasing the elephants. Solitary bulls or group of subadult males were involved in most of the attack. We found higher number of attacks outside the protected area. People who were drunk and chasing elephants using firecrackers were more vulnerable to the fatalities. In contrast, chasing elephants using fire was negatively associated with the fatalities. Elephant attacks were concentrated in proximity of forests primarily affecting the socioeconomically marginalized communities. Integrated settlement, safe housing for marginalized community, and community grain house in the settlement should be promoted to reduce the confrontation between elephants and humans in entire landscape for their long‐term survival.