Formulation and Evaluation of Chitosan-Based Ampicillin Trihydrate Nanoparticles

Purpose: To develop ampicillin trihydrate-loaded chitosan nanoparticles by modified ionic gelation method and evaluate their antimicrobial activity. Methods: Ampicillin trihydrate-loaded chitosan nanoparticles were prepared by ionic gelation method with the aid of sonication. Parameters such as the zeta potential, polydispersity, particle size, entrapment efficiency and in vitro drug release of the nanoparticles were assessed for optimization. The antibacterial properties of the nanoparticle formulation were evaluated and compared with that of a commercial formulation (reference). Results: Scanning electron microscopy revealed that the nanoparticles were in the nanosize range but irregular in shape. Concentrations of 0.35 %w/v of chitosan and 0.40 %w/v sodium tripolyphosphate (TPP) and a sonication time of 20 min constituted the optimum conditions for the preparation of the nanoparticles. In vitro release data showed an initial burst followed by slow sustained drug release. The nanoparticles demonstrated superior antimicrobial activity to plain nanoparticles and the reference, due probably to the synergistic effect of chitosan and ampicillin trihydrate. Conclusion: Modified ionic gelation method can be utilized for the development of chitosan nanoparticles of ampicillin trihydrate. Polymer and crosslinking agent concentrations and sonication time are rate-limiting factors for the development of the optimized formulation. The chitosan nanoparticles developed would be capable of sustained delivery of ampicillin trihydrate.Keywords: Ampicillin trihydrate; Chitosan; Nanoparticles; Ionic gelation method; Antibacterial activit

Effect of participatory women's groups facilitated by Accredited Social Health Activists on birth outcomes in rural eastern India: a cluster-randomised controlled trial

BACKGROUND: A quarter of the world's neonatal deaths and 15% of maternal deaths happen in India. Few community-based strategies to improve maternal and newborn health have been tested through the country's government-approved Accredited Social Health Activists (ASHAs). We aimed to test the effect of participatory women's groups facilitated by ASHAs on birth outcomes, including neonatal mortality. METHODS: In this cluster-randomised controlled trial of a community intervention to improve maternal and newborn health, we randomly assigned (1:1) geographical clusters in rural Jharkhand and Odisha, eastern India to intervention (participatory women's groups) or control (no women's groups). Study participants were women of reproductive age (15-49 years) who gave birth between Sept 1, 2009, and Dec 31, 2012. In the intervention group, ASHAs supported women's groups through a participatory learning and action meeting cycle. Groups discussed and prioritised maternal and newborn health problems, identified strategies to address them, implemented the strategies, and assessed their progress. We identified births, stillbirths, and neonatal deaths, and interviewed mothers 6 weeks after delivery. The primary outcome was neonatal mortality over a 2 year follow up. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN31567106. FINDINGS: Between September, 2009, and December, 2012, we randomly assigned 30 clusters (estimated population 156 519) to intervention (15 clusters, estimated population n=82 702) or control (15 clusters, n=73 817). During the follow-up period (Jan 1, 2011, to Dec 31, 2012), we identified 3700 births in the intervention group and 3519 in the control group. One intervention cluster was lost to follow up. The neonatal mortality rate during this period was 30 per 1000 livebirths in the intervention group and 44 per 1000 livebirths in the control group (odds ratio [OR] 0.69, 95% CI 0·53-0·89). INTERPRETATION: ASHAs can successfully reduce neonatal mortality through participatory meetings with women's groups. This is a scalable community-based approach to improving neonatal survival in rural, underserved areas of India. FUNDING: Big Lottery Fund (UK)

Formation of unique nanocrystalline Cu-In-Se bulk pn homojunctions for opto-electronic devices

Semiconductor pn junctions, integrated in optoelectronic devices require high quality crystals, made by expensive, technically difficult processes. Bulk heterojunction (BHJ) structures offer practical alternatives to circumvent the cost, flexibility and scale-up challenges of crystalline planar pn junctions. Fabrication methods for the current organic or inorganic BHJ structures invariably create interface mismatch and low doping issues. To overcome such issues, we devised an innovative approach, founded on novel inorganic material system that ensued from single-step electrodeposited copper-indium-selenide compounds. Surface analytical microscopies and spectroscopies reveal unusual phenomena, electro-optical properties and quantum effects. They support the formation of highly-ordered, sharp, abrupt 3-dimensional nanoscale pn BHJs that facilitate efficient charge carrier separation and transport, and essentially perform the same functions as crystalline planar pn junctions. This approach offers a low-cost processing platform to create nanocrystalline films, with the attributes necessary for efficient BHJ operation. It allows roll-to-roll processing of flexible devices in simple thin-film form factor.Partial funding for this work is provided by customers of Xcel Energy through a grant from the Renewable Development Fund. The authors gratefully acknowledge sample preparation, analytical contributions and useful discussions with Sharmila Menezes and Yan Li (InterPhases Solar); Senli Guo (Brucker Nano); Terrence McGuckin (Ephemeron Labs); and Nassim Rahimi (HORIBA Scientific). A. Samantilleke acknowledges Prof. L. M. Peter (Bath University, UK) for introducing EER technique

Community mobilisation with women's groups facilitated by Accredited Social Health Activists (ASHAs) to improve maternal and newborn health in underserved areas of Jharkhand and Orissa: study protocol for a cluster-randomised controlled trial

Background: Around a quarter of the world's neonatal and maternal deaths occur in India. Morbidity and mortality are highest in rural areas and among the poorest wealth quintiles. Few interventions to improve maternal and newborn health outcomes with government-mandated community health workers have been rigorously evaluated at scale in this setting.The study aims to assess the impact of a community mobilisation intervention with women's groups facilitated by ASHAs to improve maternal and newborn health outcomes among rural tribal communities of Jharkhand and Orissa.Methods/design: The study is a cluster-randomised controlled trial and will be implemented in five districts, three in Jharkhand and two in Orissa. The unit of randomisation is a rural cluster of approximately 5000 population. We identified villages within rural, tribal areas of five districts, approached them for participation in the study and enrolled them into 30 clusters, with approximately 10 ASHAs per cluster. Within each district, 6 clusters were randomly allocated to receive the community intervention or to the control group, resulting in 15 intervention and 15 control clusters. Randomisation was carried out in the presence of local stakeholders who selected the cluster numbers and allocated them to intervention or control using a pre-generated random number sequence. The intervention is a participatory learning and action cycle where ASHAs support community women's groups through a four-phase process in which they identify and prioritise local maternal and newborn health problems, implement strategies to address these and evaluate the result. The cycle is designed to fit with the ASHAs' mandate to mobilise communities for health and to complement their other tasks, including increasing institutional delivery rates and providing home visits to mothers and newborns. The trial's primary endpoint is neonatal mortality during 24 months of intervention. Additional endpoints include home care practices and health care-seeking in the antenatal, delivery and postnatal period. The impact of the intervention will be measured through a prospective surveillance system implemented by the project team, through which mothers will be interviewed around six weeks after delivery. Cost data and qualitative data are collected for cost-effectiveness and process evaluations

Protocol for the cost-consequence and equity impact analyses of a cluster randomised controlled trial comparing three variants of a nutrition-sensitive agricultural extension intervention to improve maternal and child dietary diversity and nutritional status in rural Odisha, India (UPAVAN trial)

BACKGROUND: Undernutrition causes around 3.1 million child deaths annually, around 45% of all child deaths. India has one of the highest proportions of maternal and child undernutrition globally. To accelerate reductions in undernutrition, nutrition-specific interventions need to be coupled with nutrition-sensitive programmes that tackle the underlying causes of undernutrition. This paper describes the planned economic evaluation of the UPAVAN trial, a four-arm, cluster randomised controlled trial that tests the nutritional and agricultural impacts of an innovative agriculture extension platform of women's groups viewing videos on nutrition-sensitive agriculture practices, coupled with a nutrition-specific behaviour-change intervention of videos on nutrition, and a participatory learning and action approach. METHODS: The economic evaluation of the UPAVAN interventions will be conducted from a societal perspective, taking into account all costs incurred by the implementing agency (programme costs), community and health care providers, and participants and their households, and all measurable outcomes associated with the interventions. All direct and indirect costs, including time costs and donated goods, will be estimated. The economic evaluation will take the form of a cost-consequence analysis, comparing incremental costs and incremental changes in the outcomes of the interventions, compared with the status quo. Robustness of the results will be assessed through a series of sensitivity analyses. In addition, an analysis of the equity impact of the interventions will be conducted. DISCUSSION: Evidence on the cost and cost-effectiveness of nutrition-sensitive agriculture interventions is scarce. This limits understanding of the costs of rolling out or scaling up programs. The findings of this economic evaluation will provide useful information for different multisectoral stakeholders involved in the planning and implementation of nutrition-sensitive agriculture programmes. TRIAL REGISTRATION: ISRCTN65922679 . Registered on 21 December 2016

Detrimental Effects of Non-Functional Spermatozoa on the Freezability of Functional Spermatozoa from Boar Ejaculate

In the present study, the impact of non-functional spermatozoa on the cryopreservation success of functional boar spermatozoa was evaluated. Fifteen sperm-rich ejaculate fractions collected from five fertile boars were frozen with different proportions of induced non-functional sperm (0 –native semen sample-, 25, 50 and 75% non-functional spermatozoa). After thawing, the recovery of motile and viable spermatozoa was assessed, and the functional of the spermatozoa was evaluated from plasma membrane fluidity and intracellular reactive oxygen species (ROS) generation upon exposure to capacitation conditions. In addition, the lipid peroxidation of the plasma membrane was assessed by the indirect measurement of malondialdehyde (MDA) generation. The normalized (with respect to a native semen sample) sperm motility (assessed by CASA) and viability (cytometrically assessed after staining with Hoechst 33342, propidium iodide and fluorescein-conjugated peanut agglutinin) decreased (p<0.01) as the proportion of functional spermatozoa in the semen samples before freezing decreased, irrespective of the semen donor. However, the magnitude of the effect differed (p<0.01) among boars. Moreover, semen samples with the largest non-functional sperm subpopulation before freezing showed the highest (p<0.01) levels of MDA after thawing. The thawed viable spermatozoa of semen samples with a high proportion of non-functional spermatozoa before freezing were also functionally different from those of samples with a low proportion of non-functional spermatozoa. These differences consisted of higher (p<0.01) levels of intracellular ROS generation (assessed with 5-(and-6) chloromethyl-20,70-dichlorodihydrofluorescein diacetate acetyl ester; CM-H2DCFDA) and increased (p<0.01) membrane fluidity (assessed with Merocyanine 540). These findings indicate that non-functional spermatozoa in the semen samples before freezing negatively influence the freezability of functional spermatozoa

High Efficiency Colloidal Quantum Dot Infrared Light Emitting Diodes via Engineering at the Supra-Nanocrystalline Level

Colloidal quantum dot (CQD) light-emitting diodes (LEDs) deliver a compelling performance in the visible, yet infrared CQD LEDs underperform their visible-emitting counterparts, largely due to their low photoluminescence quantum efficiency. Here we employ a ternary blend of CQD thin film that comprises a binary host matrix that serves to electronically passivate as well as to cater for an efficient and balanced carrier supply to the emitting quantum dot species. In doing so, we report infrared PbS CQD LEDs with an external quantum efficiency of ~7.9% and a power conversion efficiency of ~9.3%, thanks to their very low density of trap states, on the order of 1014 cm−3, and very high photoluminescence quantum efficiency in electrically conductive quantum dot solids of more than 60%. When these blend devices operate as solar cells they deliver an open circuit voltage that approaches their radiative limit thanks to the synergistic effect of the reduced trap-state density and the density of state modification in the nanocomposite.Peer ReviewedPostprint (author's final draft

Chitohexaose Activates Macrophages by Alternate Pathway through TLR4 and Blocks Endotoxemia

Sepsis is a consequence of systemic bacterial infections leading to hyper activation of immune cells by bacterial products resulting in enhanced release of mediators of inflammation. Endotoxin (LPS) is a major component of the outer membrane of Gram negative bacteria and a critical factor in pathogenesis of sepsis. Development of antagonists that inhibit the storm of inflammatory molecules by blocking Toll like receptors (TLR) has been the main stay of research efforts. We report here that a filarial glycoprotein binds to murine macrophages and human monocytes through TLR4 and activates them through alternate pathway and in the process inhibits LPS mediated classical activation which leads to inflammation associated with endotoxemia. The active component of the nematode glycoprotein mediating alternate activation of macrophages was found to be a carbohydrate residue, Chitohexaose. Murine macrophages and human monocytes up regulated Arginase-1 and released high levels of IL-10 when incubated with chitohexaose. Macrophages of C3H/HeJ mice (non-responsive to LPS) failed to get activated by chitohexaose suggesting that a functional TLR4 is critical for alternate activation of macrophages also. Chitohexaose inhibited LPS induced production of inflammatory molecules TNF-α, IL-1β and IL-6 by macropahges in vitro and in vivo in mice. Intraperitoneal injection of chitohexaose completely protected mice against endotoxemia when challenged with a lethal dose of LPS. Furthermore, Chitohexaose was found to reverse LPS induced endotoxemia in mice even 6/24/48 hrs after its onset. Monocytes of subjects with active filarial infection displayed characteristic alternate activation markers and were refractory to LPS mediated inflammatory activation suggesting an interesting possibility of subjects with filarial infections being less prone to develop of endotoxemia. These observations that innate activation of alternate pathway of macrophages by chtx through TLR4 has offered novel opportunities to cell biologists to study two mutually exclusive activation pathways of macrophages being mediated through a single receptor

Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.

BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis