Changes in growth,anaemia, and iron deficiency among children aged 6–23 months in two districts in Nepal that were part of the post‐pilot scale‐up of an integrated infant and young child feeding and micronutrient powder intervention

There is limited research on integrated infant and young child feeding (IYCF) and micronutrient powders (MNPs) programmes operating at scale, despite widespread implementation. This study uses cross‐sectional baseline (n = 2,542) and endline (n = 2,578) surveys representative of children 6–23 months in two districts in Nepal that were part of a post‐pilot scale‐up of a IYCF–MNP programme. Multivariable log‐binomial regression models were used to estimate prevalence ratios (PRs) for stunting (length‐for‐age z‐score <?2), wasting (weight‐for‐length z‐score <?2), underweight (weight‐for‐age z‐score <?2), anaemia (altitude‐adjusted haemoglobin <110 μg/L), moderate or severe anaemia (altitude‐adjusted haemoglobin <100 g/L), iron deficiency (inflammation‐adjusted ferritin <12 μg/L), and iron deficiency anaemia (iron deficiency + anaemia [IDA]) at endline versus baseline and also to compare children in the endline survey based on frequency of mothers' interactions with female community health volunteers (FCHVs; >1× per month or monthly vs. <1× per month) and MNP coverage (1 or ≥2 distributions vs. none among children 12–23 months). Endline children were significantly less likely to be stunted than baseline children in both districts (multivariable‐adjusted PR [95% CI]: 0.77 [0.69, 0.85], P < 0.001 and 0.82 [0.75, 0.91], P < 0.001 in Kapilvastu and Achham, respectively); however, only Achham had significantly lower prevalences of underweight, moderate/severe anaemia, iron deficiency, and IDA at endline. At endline, 53.5% and 71.4% of children had tried MNP in Kapilvastu and Achham districts, respectively, consuming an average of 24 sachets from the last distribution. Frequent maternal–FCHV interactions were associated with a reduced risk of stunting and underweight at endline, whereas repeat MNP coverage was associated with reduced risk of anaemia and IDA. Future research using experimental designs should verify the potential of integrated IYCF–MNP programmes to improve children's nutritional status.     

MRP1 and its role in anticancer drug resistance

The phenomenon of multidrug resistance (MDR) in cancer is associated with the overexpression of the ATP-binding cassette (ABC) transporter proteins, including multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein. MRP1 plays an active role in protecting cells by its ability to efflux a vast array of drugs to sub-lethal levels. There has been much effort in elucidating the mechanisms of action, structure and substrates and substrate binding sites of MRP1 in the last decade. In this review, we detail our current understanding of MRP1, its clinical relevance and highlight the current environment in the search for MRP1 inhibitors. We also look at the capacity for the rapid intercellular transfer of MRP1 phenotype from spontaneously shed membrane vesicles known as microparticles and discuss the clinical and therapeutic significance of this in the context of cancer MDR.     

KDEL peptide gold nanoconstructs: promising nanoplatforms for drug delivery

Gold nanoparticles (AuNPs) have been widely investigated as potential nanocarriers for drug delivery. In the present study, AuNPs were conjugated to a peptide that has a C-terminal Lys–Asp–Glu–Leu (KDEL) motif. In a pulse-chase study, time-course sampling revealed that AuNP-delivered KDEL peptides were rapidly localized to the endoplasmic reticulum (ER) in 5 to 15 min, and after 1 h the majority of peptides were localized to the ER. Clathrin-coated vesicles and Golgi apparatus were also involved during the intracellular trafficking of KDEL peptide gold (AuNP-KDEL) nanoconstructs. Furthermore, overexpression of KDEL receptor (KDELR) significantly enhanced KDEL peptide uptake in both free and AuNP-conjugated forms. These data indicate that the AuNP-KDEL nanoconstructs are internalized via a clathrin-mediated pathway and trafficked to the ER via a retrograde transport pathway, bypassing the lysosomal degradation pathway. Thus, this novel approach to development of nanoconstruct-based drug delivery has the potential to evade intracellular degradation, enhancing drug efficacy.From the Clinical EditorIn this study, gold nanoparticles were conjugated to a peptide with KDEL motif, resulting in internalization via a clathrin-mediated pathway and trafficking to the ER via retrograde transport meanwhile bypassing the lysosomal degradation pathway. This method results in a potential evasion of intracellular degradation, and enhanced drug efficacy.     

In vitro iontophoretic delivery of nicorandil

The present investigation is aimed at assessing the iontophoretic permeability of nicorandil to evaluate its feasibility for the development of an actively delivered transdermal system. Excised porcine skin was used for permeation study, and steady state flux was optimized with respect to donor concentration, current density, and voltage. Constant current iontophoresis was carried out at 0.3, 0.5, and 0.7 mA/cm(2), whereas constant voltage studies were carried out at 3, 5, and 6.5 V. The effect of donor drug concentration (11.8, 55.8, and 104.8 mg/mL) was studied at the optimized condition of 5 V. An apparent increase in steady state flux was observed in constant current studies, but the increment over the passive diffusion was statistically insignificant (P > 0.05). In contrast, steady state flux was found to be higher than that of passive fluxes when permeation was carried out at 5 and 6.5 V (P < 0.001). Incorporation of alcohol in the donor vehicle increased solubility, but there was a tradeoff in terms of lag time. Conformity with the Nernst-Planck convective transport model suggested that electroosmosis was the dominant mechanism of permeation.     

Screening of potential chemopreventive compounds from Poncirus trifoliata Raf

Chemopreventive agents induce a battery of genes whose protein products can protect cells from chemical-induced carcinogenesis. In this study, we isolated three different coumarins compounds (1; poncimarin, 2; heraclenol 3'-methyl ester and 3; oxypeucedanin methanolate) from Poncirus trifoliata Raf., and studied whether these compounds increase glutathione S-transferase (GST) expression and activity in the H4IIE cell-line (a rat hepatocyte cell line). CDNB (1-chloro-2,4-dinitrobenzene; GST subtype-nonspecific) and NBD (7-chloro-4-nitrobenzo-2-oxa-1,3-diazole; GSTalpha-type-specific) assays revealed that compound 1 most potently increased GST enzyme activities. Western blot analysis using subtype-specific antibodies confirmed that these three coumarins also selectively increased GSTalpha-protein expression, and that compound 1 most actively induced GSTalpha. In contrast, the expressions of the GSTmu and GSTmu subtypes were not altered by these three coumarins. Reporter gene analysis using an antioxidant response element (ARE) containing construct and subcellular fractionation assays, revealed that GSTalpha-induction by compound 1 might be associated with Nrf2/ARE activation. These results suggest that these three coumarin compounds from Poncirus trifoliata Raf possess phase II enzyme inducible functions, and in particular, that poncimarin has chemopreventive potential.     

Chiral tubule self-assembly from an achiral diynoic lipid

Tubules possessing microm-scale chiral substructure self-assemble from an achiral isomer of the tubule-forming diynoic phosphatidylcholine, 1,2-bis(10,12-tricosadiynoyl)sn-glycero-3-phosphocholine [DC(8,9)PC], showing that molecular chirality is not essential for tubule formation. CD spectroscopy shows that these structures' helical sense of handedness instead originates in a spontaneous cooperative chiral symmetry-breaking process. We conclude that the chiral symmetry-breaking must originate in the unusual feature common to the chiral and achiral tubule-forming molecules, the diynes centered in their hydrocarbon tails.     

Refractive Error Study in Children: results from Mechi Zone, Nepal

PURPOSE: To assess the prevalence of refractive error and vision impairment in school age children in the terai area of the Mechi zone in Eastern Nepal. METHODS: Random selection of village-based clusters was used to identify a sample of children 5 to 15 years of age. Children in the 25 selected clusters were enumerated through a door-to-door household survey and invited to village sites for examination. Visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and anterior segment, media, and fundus examinations were done from May 1998 through July 1998. Independent replicate examinations for quality assurance monitoring took place in all children with reduced vision and in a sample of those with normal vision in seven villages. RESULTS: A total of 5,526 children from 3,724 households were enumerated, and 5,067 children (91.7%) were examined. The prevalence of uncorrected, presenting, and best visual acuity 0.5 (20/40) or worse in at least one eye was 2.9%, 2.8%, and 1.4%, respectively; 0.4% had best visual acuity 0.5 or worse in both eyes. Refractive error was the cause in 56% of the 200 eyes with reduced uncorrected vision, amblyopia in 9%, other causes in 19%, with unexplained causes in the remaining 16%. Myopia -0.5 diopter or less in either eye or hyperopia 2 diopters or greater was observed in less than 3% of children. Hyperopia risk was associated with female gender and myopia risk with older age. CONCLUSIONS: The prevalence of reduced vision is very low in school-age children in Nepal, most of it because of correctable refractive error. Further studies are needed to determine whether the prevalence of myopia will be higher for more recent birth cohorts.     

Visual functioning and quality of life outcomes among cataract operated and unoperated blind populations in Nepal

BACKGROUND—Visual acuity and vision related quality of life outcomes in cataract surgery were evaluated in a population based survey in two geographic zones in Nepal.
METHODS—Case finding was based on random sampling using a stratified cluster design with door to door enumeration of people aged 45 years followed by eye examinations at village sites. All aphakics/pseudophakics, those with visual acuity less than 6/60 in either eye, and a sample of those with normal visual acuity were administered visual functioning (VF) and quality of life (QOL) questionnaires.
RESULTS—15% of the 159 cataract operated cases had presenting visual acuity 6/18 in both eyes, 38% with best corrected visual acuity. 21% were still blind with presenting visual acuity <6/60 in both eyes, 7% with best correction. On a 0-100 scale, mean VF and QOL scores were 87.2 and 93.9 respectively in normally sighted unoperated individuals, dropping to 15.6 and 29.5 for those severely blind (<3/60). Among the cataract operated, mean VF and QOL scores were 47.5 and 55.4, respectively. VF and QOL scores correlated with vision status at statistically significant levels (p <0.0001)
CONCLUSION—Cataract surgery outcomes, whether measured by traditional visual acuity or by patient reported VF/QOL, are at levels many would consider unacceptably low. It is apparent that in the quest to reduce cataract blindness much more attention must be given to improving surgery outcomes.

Keywords: cataract surgery; visual acuity; visual functioning; quality of life