The contribution of female community health volunteers (FCHVs) to maternity care in Nepal: a qualitative study.

BACKGROUND: In resource-poor settings, the provision of basic maternity care within health centres is often a challenge. Despite the difficulties, Nepal reduced its maternal mortality ratio by 80% from 850 to an estimated 170 per 100,000 live births between 1991 and 2011 to achieve Millennium Development Goal Five. One group that has been credited for this is community health workers, known as Female Community Health Volunteers (FCHVs), who form an integral part of the government healthcare system. This qualitative study explores the role of FCHVs in maternal healthcare provision in two regions: the Hill and Terai. METHODS: Between May 2014 and September 2014, 20 FCHVs, 11 health workers and 26 service users were purposefully selected and interviewed using semi-structured topic guides. In addition, four focus group discussions were held with 19 FCHVs. Data were analysed using thematic analysis. RESULTS: All study participants acknowledged the contribution of FCHVs in maternity care. All FCHVs reported that they shared key health messages through regularly held mothers' group meetings and referred women for health checks. The main difference between the two study regions was the support available to FCHVs from the local health centres. With regular training and access to medical supplies, FCHVs in the hill villages reported activities such as assisting with childbirth, distributing medicines and administering pregnancy tests. They also reported use of innovative approaches to educate mothers. Such activities were not reported in Terai. In both regions, a lack of monetary incentives was reported as a major challenge for already overburdened volunteers followed by a lack of education for FCHVs. CONCLUSIONS: Our findings suggest that the role of FCHVs varies according to the context in which they work. FCHVs, supported by government health centres with emphasis on the use of local approaches, have the potential to deliver basic maternity care and promote health-seeking behaviour so that serious delays in receiving healthcare can be minimised. However, FCHVs need to be reimbursed and provided with educational training to ensure that they can work effectively. The study underlines the relevance of community health workers in resource-poor settings

A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year ( with possible extension for responders). The dose was titrated according to serum calcium levels. The treatment effect was evaluated by regular CT scans. Out of 33 patients evaluable for tumour response, two had complete response (CR), 12 stable disease and 19 progressive disease. The CRs appeared after 6 and 24 months of treatment, and lasted for 29 and at least 36 months ( patient still in remission when data censored). Seocalcitol was well tolerated; the most frequent toxicity was hypercalcaemia and related symptoms. Most patients tolerated a daily dose of 10 mug of Seocalcitol. This is the first study showing activity, by reduction in tumour dimensions, of a differentiating agent in patients with an advanced bulky, solid tumour. Seocalcitol may have an effect in the treatment of HCC, especially in early disease when a prolonged treatment can be instituted. The survival benefit with or without tumour response should be determined in controlled studies

EGFR Kinase Promotes Acquisition of Stem Cell-Like Properties: A Potential Therapeutic Target in Head and Neck Squamous Cell Carcinoma Stem Cells

Members of the EGFR/ErbB family of tyrosine kinases are found to be highly expressed and deregulated in many cancers, including head and neck squamous cell carcinoma (HNSCC). The ErbB family, including EGFR, has been demonstrated to play key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these characteristics have been linked to a small subpopulation of cells classified as cancer stem cells (CSCs) which are believed to be responsible for tumor initiation and maintenance. In this study, we investigated the possible role of EGFR as a regulator of “stemness” in HNSCC cells. Activation of EGFR by the addition of EGF ligand or ectopic expression of EGFR in two established HNSCC cell lines (UMSCC-22B and HN-1) resulted in the induction of CD44, BMI-1, Oct-4, NANOG, CXCR4, and SDF-1. Activation of EGFR also resulted in increased tumorsphere formation, a characteristic ability of cancer stem cells. Conversely, treatment with the EGFR kinase inhibitor, Gefinitib (Iressa), resulted in decreased expression of the aforementioned genes, and loss of tumorsphere-forming ability. Similar trends were observed in a 99.9% CD44 positive stem cell culture derived from a fresh HNSCC tumor, confirming our findings for the cell lines. Additionally, we found that these putative cancer stem cells, when treated with Gefitinib, possessed a lower capacity to invade and became more sensitive to cisplatin-induced death in vitro. These results suggest that EGFR plays critical roles in the survival, maintenance, and function of cancer stem cells. Drugs that target EGFR, perhaps administered in combination with conventional chemotherapy, might be an effective treatment for HNSCC

In vivo incorporation of fenfluramine and norfenfluramine into pigmented and nonpigmented hair of rats measured by HPLC-fluorescence detection

The incorporation profiles for fenfluramine (Fen) and its metabolite norfenfluramine (Norf) into black hair and white hair of Zucker rats and into white hair of Wistar rats after intraperitoneal (i.p.) administration of Fen or N-nitrosofenfluramine (N-Fen) were studied in great detail. The target compounds were determined by high-performance liquid chromatography with fluorescence detection using 4-(4,5-diphenyl-1 H-imidazol-2-yl)benzoyl chloride as a derivatization reagent. After repeated i.p. administration of Fen (5 mg/kg) for 4 days to Zucker rats, shaft and root samples of black and white hair were obtained 1 week after the first administration. It was surprising that Fen and Norf levels in root samples of white hair were much higher than those in shaft or root samples of black hair, strongly suggesting that unknown mechanisms other than the action of melanin take place in the white hair root. Time course profiles for Fen and Norf after administration of a single i.p. dose of Fen or N-Fen were constructed for Zucker and Wistar rats. The percent level of Fen or Norf in white hair was 15-50% of that in black hair at any interval within 600 min after a single administration of Fen in Zucker rats. Even with Wistar rats having only white hair, we could demonstrate the time courses for incorporation of Fen and Norf into white hair. Finally, time course profiles for Fen and Norf were also followed after a single i.p. administration of N-Fen; this experiment showed that the levels of Norf were much higher than those of Fen for both black and white hair samples of Zucker rats at any interval tested

On Randomizing Hash Functions to Strengthen the Security of Digital Signatures

Halevi and Krawczyk proposed a message randomization algorithm called RMX as a front-end tool to the hash-then-sign digital signature schemes such as DSS and RSA in order to free their reliance on the collision resistance property of the hash functions. They have shown that to forge a RMX-hash-then-sign signature scheme, one has to solve a cryptanalytical task which is related to finding second preimages for the hash function. In this article, we will show how to use Dean’s method of finding expandable messages for finding a second preimage in the Merkle-Damgård hash function to existentially forge a signature scheme based on a t-bit RMX-hash function which uses the Davies-Meyer compression functions (e.g., MD4, MD5, SHA family) in 2 t/2 chosen messages plus 2 t/2 + 1 off-line operations of the compression function and similar amount of memory. This forgery attack also works on the signature schemes that use Davies-Meyer schemes and a variant of RMX published by NIST in its Draft Special Publication (SP) 800-106. We discuss some important applications of our attack

Candida albicans-produced farnesol stimulates Pseudomonas quinolone signal production in LasR-defective Pseudomonas aeruginosa strains

Candida albicans has been previously shown to stimulate the production of Pseudomonas aeruginosa phenazine toxins in dual-species colony biofilms. Here, we report that P. aeruginosa lasR mutants, which lack the master quorum sensing system regulator, regain the ability to produce quorum-sensing-regulated phenazines when cultured with C. albicans. Farnesol, a signalling molecule produced by C. albicans, was sufficient to stimulate phenazine production in LasR− laboratory strains and clinical isolates. P. aeruginosa ΔlasR mutants are defective in production of the Pseudomonas quinolone signal (PQS) due to their inability to properly induce pqsH, which encodes the enzyme necessary for the last step in PQS biosynthesis. We show that expression of pqsH in a ΔlasR strain was sufficient to restore PQS production, and that farnesol restored pqsH expression in ΔlasR mutants. The farnesol-mediated increase in pqsH required RhlR, a transcriptional regulator downstream of LasR, and farnesol led to higher levels of N-butyryl-homoserine lactone, the small molecule activator of RhlR. Farnesol promotes the production of reactive oxygen species (ROS) in a variety of species. Because the antioxidant N-acetylcysteine suppressed farnesol-induced RhlR activity in LasR− strains, and hydrogen peroxide was sufficient to restore PQS production in las mutants, we propose that ROS are responsible for the activation of downstream portions of this quorum sensing pathway. LasR mutants frequently arise in the lungs of patients chronically infected with P. aeruginosa. The finding that C. albicans, farnesol or ROS stimulate virulence factor production in lasR strains provides new insight into the virulence potential of these strains