Synthesis and antitumor activities of aquayamycin and analogues of derhodinosylurdamycin A.

Total syntheses of aquayamycin (3) and a number of analogues of angucycline antitumor antibiotic derhodinosylurdamycin A bearing various 2-deoxy sugar subunits (4-7) have been achieved. These molecules (3-7) were synthesized based on a convergent strategy for the synthesis of derhodinosylurdamycin A (2) previously reported from our group. In particular, our recently developed mild cationic gold-catalyzed glycosylation with S-but-3-ynyl thioglycoside donors was employed for the synthesis of analogues (6 and 7) bearing disaccharide subunits containing α-l-olivoside and α-l-olioside moiety, respectively. Aquayamycin (3), analogues (4-7), and our previously synthesized derhodinosylurdamycin A (2) were then submitted to the Development Therapeutics Program of the National Cancer Institute of National Institutes of Health for the NCI-60 Human Tumor Cell Lines Screening using standard protocols. It was found that derhodinosylurdamycin A (2), aquayamycin (3), and three other analogues (5-7) bearing sugar subunits did not show significant antiproliferative activity against those cancer cell lines. Interestingly, analogue (4) bearing no sugar subunit demonstrates good potential for growth inhibition and cytotoxic activity against a variety of human cancer cell lines.

Reduced healthcare utilization following successful hepatitis C virus treatment in HIV-co-infected patients with mild liver disease.

New direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection have achieved high cure rates in many patient groups previously considered difficult-to-treat, including those HIV/HCV co-infected. The high price of these medications is likely to limit access to treatment, at least in the short term. Early treatment priority is likely to be given to those with advanced disease, but a more detailed understanding of the potential benefits in treating those with mild disease is needed. We hypothesized that successful HCV treatment within a co-infected population with mild liver disease would lead to a reduction in the use and costs of healthcare services in the 5 years following treatment completion. We performed a retrospective cohort study of HIV/HCV-co-infected patients without evidence of fibrosis/cirrhosis who received a course of HCV therapy between 2004 and 2013. Detailed analysis of healthcare utilization up to 5 years following treatment for each patient using clinical and electronic records was used to estimate healthcare costs. Sixty-three patients were investigated, of whom 48 of 63 (76.2%) achieved sustained virological response 12 weeks following completion of therapy (SVR12). Individuals achieving SVR12 incurred lower health utilization costs (£5,000 per-patient) compared to (£10 775 per-patient) non-SVR patients in the 5 years after treatment. Healthcare utilization rates and costs in the immediate 5 years following treatment were significantly higher in co-infected patients with mild disease that failed to achieve SVR12. These data suggest additional value to achieving cure beyond the prevention of complications of disease.

Ethical approval in developing countries is not optional.

When conducting health and medical research it is important to do the research ethically and to apply for prior ethical approval from the relevant authorities. The latter requirement is true for developed countries as well as developing countries. The authors argue that simply applying for research ethics approval from an institutional review board at a university based in a developed country is not enough to start a health research project in a developing country. The paper also suggests a number of reasons why researchers may fail to seek local research ethics permission in developing countries. The authors use a recent paper reporting research conducted in Nepal and published in an international journal as a case study to highlight the importance of being sensitive to local requirements regarding applying for and registering health and medical research.

Facile Synthesis of Sugar Lactols via Bromine-Mediated Oxidation of Thioglycosides.

Synthesis of a variety of sugar lactols (hemiacetals) has been accomplished in moderate to excellent yields by using bromine-mediated oxidation of thioglycosides. It was found that acetonitrile is the optimal solvent for this oxidation reaction. This approach involving bromine as oxidant is superior to that using N-bromosuccimide (NBS) which produces byproduct succinimide often difficult to separate from the lactol products.

Health and lifestyle of Nepalese migrants in the UK.

BACKGROUND: The health status and lifestyle of migrants is often poorer than that of the general population of their host countries. The Nepalese represent a relatively small, but growing, immigrant community in the UK, about whom very little is known in term of public health. Therefore, our study examined the health and lifestyle of Nepalese migrants in the UK. METHODS: A cross-sectional survey of Nepalese migrants in UK was conducted in early 2007 using a postal, self-administered questionnaire in England and Scotland (n = 312), and telephone interviews in Wales (n = 15). The total response rate was 68% (327 out of 480). Data were analyzed to establish whether there are associations between socio-economic and lifestyle factors. A multivariate binary logistic regression was applied to find out independent effect of personal factors on health status. RESULTS: The majority of respondents was male (75%), aged between 30 and 45 (66%), married or had a civil partner (83%), had university education (47%) and an annual family income (69%) ranging from pound5,035 to pound33,300. More than one third (39%) of the respondents have lived in the UK for 1 to 5 years and approximately half (46%) were longer-term residents. Most (95%) were registered with a family doctor, but only 38% with a dentist. A low proportion (14%) of respondents smoked but more than half (61%) consumed alcohol. More than half (57%) did not do regular exercises and nearly one fourth (23%) of respondents rated their health as poor. Self reported 'good' health status of the respondents was independently associated with immigration status and doing regular exercise CONCLUSION: The self reported health status and lifestyle, health seeking behaviour of Nepalese people who are residing in UK appears to be good. However, the overall regular exercise and dentist registration was rather poor. Health promotion, especially aimed at Nepalese migrants could help encourage them to exercise regularly and assist them to register with a dentist.

Utilisation of postnatal care among rural women in Nepal.

BACKGROUND: Postnatal care is uncommon in Nepal, and where it is available the quality is often poor. Adequate utilisation of postnatal care can help reduce mortality and morbidity among mothers and their babies. Therefore, our study assessed the utilisation of postnatal care at a rural community level. METHODS: A descriptive, cross-sectional study was carried out in two neighbouring villages in early 2006. A total of 150 women who had delivered in the previous 24 months were asked to participate in the study using a semi-structured questionnaire. RESULTS: The proportion of women who had received postnatal care after delivery was low (34%). Less than one in five women (19%) received care within 48 hours of giving birth. Women in one village had less access to postnatal care than women in the neighbouring one. Lack of awareness was the main barrier to the utilisation of postnatal care. The woman's own occupation and ethnicity, the number of pregnancies and children and the husband's socio-economic status, occupation and education were significantly associated with the utilisation of postnatal care. Multivariate analysis showed that wealth as reflected in occupation and having attended antenatal are important factors associated with the uptake of postnatal care. In addition, women experiencing health problems appear strongly motivated to seek postnatal care. CONCLUSION: The postnatal care has a low uptake and is often regarded as inadequate in Nepal. This is an important message to both service providers and health-policy makers. Therefore, there is an urgent need to assess the actual quality of postnatal care provided. Also there appears to be a need for awareness-raising programmes highlighting the availability of current postnatal care where this is of sufficient quality.

Neurobrucellosis Presenting as Pseudotumor Cerebri: First Report from Oman.

A ten-year-old boy presented to the hospital with body ache and joint pains for two months and headache, vomiting, and skin rash for three days. He was drowsy and lethargic at admission. Physical examination revealed bilateral papilledema. There were no cranial nerve involvement, neuromotor deficit, or signs of meningeal irritation. Computed tomography and magnetic resonance imaging of the brain did not reveal any evidence of cerebral edema or space occupying lesion. In view of the high endemicity of brucellosis in the area, Brucella agglutination test (BAT) was done at the time of admission and was negative. However, on the eighth day of admission, blood culture showed growth of Brucella melitensis. A repeat BAT at this time was strongly positive with a titer of 1:1 280. The initial one was negative due to prozone phenomenon caused by very high antibody titers. A diagnosis of neurobrucellosis with pseudotumor cerebri was made. He was treated with gentamicin, rifampicin, and septrin along with acetazolamide for raised intracranial pressure. The boy responded well to therapy and made a complete clinical recovery with resolution of papilledema. In areas endemic for brucellosis, a high index of suspicion for neurobrucellosis should be entertained in any child presenting with diverse neurological signs.

Identifying the gaps in Nepalese migrant workers' health and well-being: a review of the literature.

BACKGROUND: The health and well-being of migrant workers from low-income countries is often neglected in travel medicine. This article uses Nepal as a case study to highlight key issues affecting this particular group of international travellers. METHODS: This narrative review used a comprehensive systematic literature search to identify relevant studies on Nepal. The included articles were thematically analysed leading to four key themes or risk factors. RESULTS: The search found 18 articles from which we identified 3 key themes related directly to migrant workers: (1) sexual risk taking; (2) occupational health and (3) lifestyles, and a fourth theme related to partners and family of migrant workers who are left behind in Nepal. Of the 18 included articles, 11 articles discussed sexual risk taking and HIV, whilst considerably fewer focused on work-related risk factors and lifestyle factors in migrant workers. CONCLUSIONS: Migrant workers who are generally healthy appear to be similar to tourist travellers in regarding sexual health as a key issue related to being abroad. Risky sexual behaviour increases in individuals separated from their usual sexual partners, away from their own communities and families, leading to the so-called 'situational disinhibition'. Considering the recent media coverage of deaths and injuries among migrant workers in the Middle East, it is interesting to see that their sexual health is more prevalent in the research literature. This article argues that travel medicine should provide more emphasis to the health and well-being of migrant workers as a highly vulnerable group of travellers with additional impact on the health of those left behind.

Synthesis of S-linked trisaccharide glycal of derhodinosylurdamycin A: Discovery of alkyl thiocyanate as an efficient electrophile for stereoselective sulfenylation of 2-deoxy glycosyl lithium.

Stereoselective synthesis of S-linked trisaccharide glycal of angucycline antitumor antibiotic derhodinosylurdamycin A is described. The synthesis has been accomplished employing our previously reported umpolung S-glycosylation strategy - stereoselective sulfenylation of 2-deoxy glycosyl lithium. It was found that sugar-derived thiocyanate was a better electrophile than corresponding asymmetric disulfide in this type of stereoselective sulfenylation.

Factors Influencing Sexual Behaviour Between Tourists and Tourism Employees: A Systematic Review.

BACKGROUND: Increased travel abroad has a significant impact on the incidence and prevalence of Sexually Transmitted Infections (STIs). Previous reviews have focused on the knowledge, attitudes and behaviour of tourists and acquisition of STIs. Less is known about the impact on tourism operators in countries visited by tourists. The aim of this review is to ascertain factors influencing sexual behaviour between workers in the tourism industry and tourists; exploring the prevalence of sexual behaviour between the two populations, their perceptions of sexual risk while engaging in sexual activities and the knowledge of tourism operators regarding STIs. METHODS: A systematic review was conducted. Database searches were performed in Medline/Ovid, EMBASE, Cochrane library and CINAHL for studies published between 2000 and March 2016. Grey literature searches were completed in the NHS database and Google Scholar between 2000 and December 2013. Papers were independently selected by two researchers. Data were extracted and critically appraised using a pre-designed extraction form and adapted CASP checklist. RESULTS: The search identified 1,602 studies and 16 were included after review of the full text. Studies were conducted in nine countries. Findings suggest that STI knowledge, attitude and practice were fairly good among tourists and tourism workers, but there is a need for pre-travel advice for travellers, especially those travelling to low and middle-income countries. Greater importance was given to tourists than to tourism operators and locals interacting with tourists. Studies suggest that as a group both tourist and tourist workers were likely to engage in sexual activities. Overall, both condom use and STI screening were low, among tourists as well as tourism operators. Furthermore, studies reported links between drug and alcohol use and sexual behaviour and risk taking. CONCLUSION: Although less research appeared to have been conducted among tourism workers than tourists, it does demonstrate the need for education, training and promotion of travel medicine. STI screening, pre-travel advice, travel history in terms of contracting STIs and safe-sex awareness-raising are needed. More and better sexual health education and relevant tourism policies are needed globally.

Women's knowledge of and attitude towards disability in rural Nepal.

PURPOSE: What is perceived to be a disability is both culturally specific and related to levels of development and modernity. This paper explores knowledge and attitudes towards people with disabilities among rural women in Nepal, one of the poorer countries in South Asia. METHOD: Four hundred and twelve married women of reproductive age (aged 15-49 years), from four villages in two different parts of Nepal, who had delivered a child within the last 24 months preceding the study, completed a standard questionnaire. RESULTS: The majority of the participants only considered physical conditions that limit function of an individual and are visible to naked eyes, such as missing a leg or arm, to be disability. Attitudes towards people with disability were generally positive, for example most women believed that disabled people should have equal rights and should be allowed to sit on committees or get married. Most respondents thought that disability could result from: (i) accidents; (ii) medical conditions; or (iii) genetic inheritance. Fewer women thought that disability was caused by fate or bad spirits. CONCLUSIONS: There is need to educate the general population on disability, especially the invisible disabilities. There is also a need for further research on disability and its social impact. IMPLICATIONS FOR REHABILITATION: • There is need to educate the general population on disability, especially the invisible disabilities and its rehabilitation. There is also a need for further research on disability and its social impact.

Knowledge, attitude, and prevalence of overweight and obesity among civil servants in Nepal.

Obesity threatens developing countries as urbanization increases, with civil servants being particularly vulnerable. The authors assess overweight/obesity prevalence among Nepalese civil servants along with their knowledge and attitudes. A cross-sectional questionnaire survey conducted among 341 participants (97.4% response rate) also recorded height and weight. Participants were 40 ± 6.6 years, mostly males, married, and from a single ethnic group. Overweight/obesity prevalence was 33.4%. Knowledge of obesity was good. However, some attitudes toward obese people were negative, despite half of the participants believing obesity to indicate prosperity. Logistic regression indicated marriage and/or having a better job increased the overweight/obese risk by nearly 8 and 9 times, respectively. Heavier people were more likely to disagree with attitudes that obese people were "lazier" and "untidy." Obesity prevalence among Nepalese civil servants is already higher than the general population level. Health education and interventions are needed to translate knowledge into attitude and behavior changes in order to prevent this becoming an epidemic.

Health and medical research in Nepal: a bibliometric review.

This study aimed to quantify the following: (1) health research in academic journals covering Nepal, (2) location of authors, and (3) most prevalent specialties. Published health research conducted in Nepal during 1996 to May 2007 was assessed by searching from 4 electronic databases, and 631 research articles met the inclusion criteria. Only 11% was published in Nepalese journals. Most research covered urban districts. About two thirds of articles had Nepalese authors, but only 41% had a Nepalese first author. Child health and nutrition (11%), maternal health and women's health (11%), and sexual reproductive health and HIV/AIDS, and family planning (11%) were the most common topics. Most articles (78%) reported quantitative methods. The number of research articles from Nepal is fairly small and concentrated on a limited number of topics and districts. Strategic planning is required to improve the research capacity of Nepal to achieve public health improvements using locally produced evidence.