Sociodemographic factors affecting not receiving COVID-19 vaccine in Japan among people who originally intended to vaccinate: a prospective cohort study.

Objective: Vaccine hesitancy is a major issue for acquiring herd immunity. However, some individuals may go unvaccinated owing to inhibitory factors other than vaccine hesitancy. If there is even a small number of such people, support is needed for equitable vaccine distribution and acquiring herd immunity. We investigated sociodemographic factors that affected not undergoing COVID-19 vaccination in Japan among individuals who had strong intention to vaccinate before beginning the vaccination. Methods: We conducted this prospective cohort study on workers aged 20-65 years from December 2020 (baseline), to December 2021 using a self-administered questionnaire survey. There were 27,036 participants at baseline and 18,560 at follow-up. We included 6,955 participants who answered yes to this question at baseline: "Would you like to receive a COVID-19 vaccine as soon as it becomes available?" We applied multilevel logistic regression analyses to examine the association between sociodemographic factors and being unvaccinated at follow-up. Results: In all, 289 participants (4.2%) went unvaccinated. The odds ratios (ORs) for being unvaccinated were significantly higher for participants aged 30-39 and 40-49 than those aged 60-65 years. Being divorced, widowed, or single, having low income, and having COVID-19 infection experience also had higher ORs. Discussion: We found that some participants who initially had strong intention to vaccinate may have gone unvaccinated owing to vaccine side effects and the financial impact of absenteeism due to side effects. It is necessary to provide information repeatedly about the need for vaccination as well as social support to ensure that those who intend to vaccinate are able to do so when aiming for acquiring herd immunity through vaccination against COVID-19 as well as other potential infection pandemics in the future.

Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

Health-related quality of life in parous women with pelvic organ prolapse and/or urinary incontinence in Bangladesh.

INTRODUCTION AND HYPOTHESIS: We assessed the association of pelvic organ prolapse (POP) and urinary incontinence (UI), alone and in combination (POP-UI), and related factors with health-related quality of life (HRQOL) in parous women in Bangladesh. METHODS: The study included 357 parous women: 107 with POP alone, 124 with POP-UI, and 126 with UI alone. Data were collected on sociodemographic characteristics, comorbidities, symptom duration, UI severity and type, POP stage, and the 12-item Short-Form Health Survey (SF-12). RESULTS: The median scores of the SF-12 Physical and Mental Component Summary (PCS and MCS) were 29.1 and 35.7 for POP alone, 28.0 and 35.1 for POP-UI, and 33.9 and 42.0 for UI alone, and there were significant differences among the three groups (p < 0.001). Participants with mixed UI had lower scores on both components than those with stress or urgency UI. UI severity was associated with lower MCS scores, but not with POP stage. Multiple regression analysis showed that the coexistence of POP and UI was associated with significantly worse PCS scores than UI or POP alone and worse MCS scores than UI alone. Age ≥ 46 years was associated with lower PCS scores, and not completing primary school was associated with lower MCS scores. CONCLUSION: POP and UI were associated with HRQOL, especially in those who had POP-UI, were older, and had a low educational level, mixed UI, and severe UI. Healthcare providers should understand the significance of these illnesses and address them to improve women's HRQOL.

Experiences of romantic relationships and desires to marry and have children among youth in a low-fertility society.

Introduction: This study aims to explore experiences of romantic relationships and to examine determinants of desires to marry and have children in the future among Japanese university students. Methods: A cross-sectional study was conducted among undergraduate students of A University, located in the capital city of a Japanese prefecture, using an anonymous self-administered and structured questionnaire developed by an online survey software. Results: A total of 815 respondents with complete data were analyzed by logistic regression analysis. Over 80% of males and females expressed the desire to marry and have children in the future. It was found that for both female and male respondents, the "desire to marry" was associated with currently being in a romantic relationship or having experience of sexual intercourse. On the contrary, the "desire to have children" was associated with currently being in a romantic relationship or having experience of sexual intercourse only among male respondents, and no significant association was observed among female respondents. Conclusion: "Currently being in a romantic relationship" and "having experience of sexual intercourse" were associated with wanting to marry and have children in the future among male university students. This suggests that these may be important factors in providing a positive perception regarding having children when they attain childbearing age.

Perception and practice of 'healthy' diet in relation to noncommunicable diseases among the urban and rural people in northern Ethiopia: a community-based qualitative study.

Dietary habits are related to the risks of noncommunicable diseases (NCDs), such as cardiovascular disease and diabetes, of which burdens are increasing in low-income countries including Ethiopia. Although several epidemiological studies of NCD risk factors were conducted in Ethiopia, qualitative studies on people's dietary habit in relation to NCDs have not been conducted yet. This study aims to describe people's perception and practice of 'healthy' diet, and barriers to practice 'healthy' diet, paying attention to the dynamics between the perception and practice. We conducted 16 key informant interviews and eight focus group discussions in an urban and a rural areas in northern Ethiopia between November 2014 and January 2016. Audio-records in local language were transcribed word-for-word, and translated into English. English text data were analyzed qualitatively, through constant comparative analysis following the principles of the grounded theory. Three themes have emerged: (1) dietary habit perceived as 'good' or 'bad' for health; (2) reasons for continuing current 'unhealthy' dietary habit; and (3) current dietary habit perceived as 'traditional.' People's practice was mostly consistent with their perception, while they sometimes practiced contrary to the perception because of personal preference and physical or financial obstacles. People were often indifferent of health implications of their habitual dietary practice, such as drinking a lot of sweet coffee. We showed dynamics between perception and practice of 'healthy' diet among people in northern Ethiopia. It is needed to increase awareness of NCDs both among the urban and rural people and to improve the social environment for removing the obstacles.

Perceptions and behavior related to noncommunicable diseases among slum dwellers in a rapidly urbanizing city, Dhaka, Bangladesh: a qualitative study.

The increasing burden of noncommunicable diseases (NCDs) in Bangladesh can be attributable to rapid urbanization and coinciding changes in lifestyle accompanied by nutrition transition. The objective of this study is to explore respondents' lived experiences and perceptions relating to NCDs and nutrition change in an urban slum community in Dhaka. Qualitative methods were employed to explore a general understanding of behavior related to NCDs among residents of the slum community. We conducted key informant interviews of six men and seven women of various backgrounds and five focus group discussions to focus salient topics emerged from the interviews. The transcriptions of the audio-recordings were thematically analyzed, using the constant comparison method. Four major themes emerged: (1) financial hardship influencing health; (2) urbanized lifestyle affecting diet; (3) tobacco and sweetened tea as cornerstones of social life; and (4) health-seeking behavior utilizing local resources. One notable finding was that even with general economic improvement, respondents perceived poverty to be one of the major causes of NCDs. A promising finding for potentially curbing NCDs was the current trend for women to walk for exercise contrary to the commonly held notion that urban dwellers generally lead sedentary lifestyles. This study described how urban slum dwellers in Dhaka, experiencing a transition from a traditional to urbanized lifestyle, perceived their daily practices in relation to NCDs and nutrition. Our research revealed both adverse and encouraging elements of perceptions and behavior related to NCDs, which may contribute to the optimal design of NCD prevention and health promotion programs.

Prevalence of non-communicable disease risk factors among poor shantytown residents in Dhaka, Bangladesh: a community-based cross-sectional survey.

OBJECTIVES: This study aims to describe the prevalence of non-communicable disease (NCD) risk factors among the urban poor in Bangladesh. DESIGN: We conducted a community-based cross-sectional epidemiological study. SETTING: The study was conducted in a shantytown in the city of Dhaka. There were 8604 households with 34 170 residents in the community. Those households were categorised into two wealth strata based on the housing structure. PARTICIPANTS: The study targeted residents aged 18-64 years. A total of 2986 eligible households with one eligible individual were selected by simple random sampling stratified by household wealth status. A total of 2551 residents completed the questionnaire survey, and 2009 participated in the subsequent physical and biochemical measurements. OUTCOME MEASURES: A modified WHO survey instrument was used for assessing behavioural risk factors and physical and biochemical measurements, including glycated haemoglobin (HbA1c). The prevalence of NCD risk factors, such as tobacco use, fruit and vegetable intake, overweight/obesity, hypertension, diabetes (HbA1c ≥6.5%) and dyslipidaemia, was described according to household wealth status and gender differences. RESULTS: The prevalence of current tobacco use was 60.4% in men and 23.5% in women. Most of them (90.8%) consumed more than 1 serving of fruits and vegetables per day; however, only 2.1% consumed more than 5 servings. Overweight/obesity was more common in women (39.2%) than in men (18.9%), while underweight was more common in men (21.0%) than in women (7.1%). The prevalence of hypertension was 18.6% in men and 20.7% in women. The prevalence of diabetes was 15.6% in men and 22.5% in women, which was much higher than the estimated national prevalence (7%). The prevalence of raised total cholesterol (≥190 mg/dL) was 25.7% in men and 34.0% in women. CONCLUSION: The study identified that tobacco use, both overweight and underweight, diabetes, hypertension and dyslipidaemia were prevalent among the urban poor in Bangladesh.

Population profile and residential environment of an urban poor community in Dhaka, Bangladesh.

OBJECTIVES: A population survey was conducted in an urban shantytown in Bangladesh, as a baseline study of future epidemiological studies. This paper aims to describe the findings of the study, including the population profile and residential environment of the urban poor. METHODS: We conducted a complete count household survey in an urban poor community in Dhaka. Using a brief structured questionnaire in Bengali language, trained interviewers visited each household and asked questions such as: duration of residence; ownership of house, toilet and kitchen; water supply; number of family members; age, sex, education, occupation, tobacco use, and history of diseases of each family member. RESULTS: We found that there were 8604 households and 34,170 people in the community. Average number of household members was 4.0. Most people had access to safe water, but only 16% lived in the house with a toilet. Based on the proxy indicators of household wealth levels, we identified that about 39% were relatively well-off, while the rest were very poor. Tobacco use was prevalent in men regardless of age and in women aged over 35 years. Prevalence of self-reported hypertension and diabetes was slightly higher in women than in men, although over 70% of the respondents didn't know if they had such diseases. Incidences of diarrhea in the last one month were relatively low. CONCLUSIONS: The study showed population profile and sanitation environment in an urban poor community by a complete count survey. We expect the study to serve as a baseline for future epidemiological studies.

Effect of Nerve Growth Factor on Innervation of Perivascular Nerves in Neovasculatures of Mouse Cornea.

Angiogenesis, which is the generation of new vascular networks from existing blood vessels, occurs under normal and pathophysiological conditions. Perivascular nerves, which innervate mature vasculatures, maintain vascular tone and regulate tissue blood flow. However, little is known whether perivascular nerves innervate newborn blood vessels. Therefore, the aim of this study was to investigate the distribution and characterization of perivascular nerves in neovasculatures, which were generated by the mouse corneal micropocket method. Under anesthesia, a pellet containing basic fibroblast growth factor (bFGF) (100 ng/pellet) was implanted into a mouse cornea in one side of the eyeball. Nerve growth factor (NGF) was locally (2 or 20 ng) applied with the pellet, or subcutaneously (40 ng/h for 7 d) administered with an osmotic mini-pump. After the implantation, vascular endothelial cells, smooth muscle cells, and perivascular nerves in the cornea were immunohistochemically studied. Neovessels generated from existing limbal vessels were observed in pellet-implanted cornea. Immunostaining of neovasculatures showed the presence of CD31-like immunoreactive (LI) endothelial cells and α-smooth muscle actin-LI vascular smooth muscles. Perivascular nerves immunostained by protein gene product (PGP) 9.5, an axonal marker, were found in the existing limbal vessels, but they were not observed in neovasculatures. Local and subcutaneous treatment of NGF inhibits bFGF-derived angiogenesis and resulted in loop-shaped vessels that had many anastomoses, and produced innervation of PGP 9.5-LI perivascular nerves around bFGF-derived neovessels. These findings suggest that neovasculatures have no innervation of perivascular nerves, and that NGF facilitates innervations of perivascular nerves to regulate the blood flow in neovessels.

Nerve Growth Factor Facilitates the Innervation of Perivascular Nerves in Tumor-Derived Neovasculature in the Mouse Cornea.

BACKGROUND: Tumor neovascular vessels are not innervated by perivascular nerves. This study was an investigation of the effects of the nerve growth factor (NGF) on the distribution of perivascular nerves and neovessel formation in tumor tissues. METHODS: A gel containing DU145 prostate carcinoma cells or HT1080 fibrosarcoma cells was implanted into mouse corneas. NGF was subcutaneously administered using an osmotic mini-pump. The distribution of perivascular nerves in mouse corneas and densities of CD31-immunopositive neovessels and smooth muscles (α-smooth muscle actin, α-SMA) in tumor tissues were quantified. SUMMARY: Neovessels generated from corneal limber arteries in tumor tissues were observed 4-14 days after the implantation of tumor cells. The density of CD31-immunopositive cells in endothelium increased after the implantation of DU145 or HT1080 cells, while that of α-SMA-immunopositive cells slightly increased. The NGF treatment significantly increased the density of α-SMA- but not that of CD31-immunopositive cells (except for DU145 cells) and resulted in the innervation of perivascular nerves around tumor-derived neovessels, whereas no innervation was observed in the control group. Key Messages: These results suggest that NGF facilitates the innervation of perivascular nerves to regulate blood flow into tumor-derived neovessels.

Health-related quality of life among women in rural Bangladesh after surgical repair of obstetric fistula.

OBJECTIVE: To identify factors influencing health-related quality of life (QOL) among women in Bangladesh after successful surgical repair of obstetric fistula. METHODS: In 2012, a cross-sectional study was conducted of women who had undergone a successful surgical repair of an obstetric fistula at a hospital in northwest Bangladesh between June 2005 and May 2012. Sociodemographic, obstetric, and fistula-related information was collected by interview. Health-related QOL was assessed using the 36-item Short Form Health Survey (SF-36). RESULTS: A total of 113 women were included. Linear regression analysis showed that discrimination experiences negatively affected four of the eight scales of SF-36, as well as both the physical and mental component summaries (P<0.05 for all). Married status had a positive effect on four scales and the mental component summary (P<0.05 for all). Age inversely affected two scales and the physical component summary (P<0.01 for all). Internalized stigma negatively influenced two scales (P<0.05 for both). Not having living children and experiencing two or more previous stillbirths negatively influenced one scale (P<0.05 for both). CONCLUSION: Several factors influence health-related QOL after obstetric fistula repair; a comprehensive approach is needed to address these issues.

Association between social support and place of delivery: a cross-sectional study in Kericho, Western Kenya.

BACKGROUND: An estimated 358,000 maternal deaths still occur worldwide each year. The place of delivery is of great significance to the reduction of maternal mortality. Moreover, socio-economic factors, cultural traits, and local customs are associated with health-seeking behavior. This study aimed to explore determinants of association between social support and place of delivery. METHODS: This cross-sectional study was conducted from September to November 2011 at Sosiot Health Center, Kericho West District, Kenya. Participants were 303 mothers who brought their babies to the health center for immunization within their first year of life. Women underwent a structured interview using a questionnaire on demographic characteristics and their experiences of delivery including place of delivery and social support. RESULTS: The proportion of deliveries at health facilities was significantly higher in unmarried than married women (93% and 78%, respectively; P = 0.008). Unmarried women whose mothers supported them in housework and whose sisters helped them fetch water were more likely to deliver at health facilities (P = 0.002 and 0.042, respectively) than those without this support. However, married women whose husbands supported them in farming and whose neighbors helped them fetch water were less likely to deliver at health facilities (P = 0.003 and 0.021, respectively) than those without this support. Married women who were advised to deliver at a health facility by their mother-in-law or health staff were more likely to deliver at health facilities (P = 0.015 and 0.022, respectively) than those who did not receive this advice. Multivariate analysis revealed that married women were more likely to deliver at health facilities if they were highly educated (odds ratio [OR] = 2.5); had financial capability (OR = 4.3); had medical insurance (OR = 4.2); were primiparous (OR = 3.5); did not have the support of sisters-in-law for fetching water (OR = 2.2); or were advised to deliver at a health facility by family or neighbors (OR = 2.5). CONCLUSIONS: Promotion of delivery at health facilities requires approaches that consider women's social situation, since factors influencing place of delivery differ for married and unmarried women.

Factors associated with facility-based delivery in Mayoyao, Ifugao Province, Philippines.

BACKGROUND: The maternal mortality ratio (MMR) in the Philippines is higher than in most other Southeast Asian countries, and home delivery is a major factor contributing to the high MMR. This study aims to explore the determinants for choice of delivery location in Ifugao Province, where people have poor access to health services. FINDINGS: A household interview survey using a structured questionnaire was conducted to identify the factors associated with delivery location among 354 women. In all, 44.4% of the respondents delivered at a health facility. Using logistic regression analysis, parity (odds ratio [OR] 3.0, 95% confidence interval [C.I.] 1.6-5.6), higher education (OR 5.9, 95% C.I. 2.7-12.9), distance to a health facility (OR 6.9, 95% C.I. 3.4-14.2), health problems identified at antenatal care (OR 2.4, 95% C.I. 1.3-4.6), and the person deciding on the delivery location (e.g., for the husband OR 3.2, 95% C.I. 1.1-9.4) were found to be statistically associated with facility-based delivery. CONCLUSION: Involving the husband and other people in the decision regarding delivery location may influence a woman's choice to use facility-based delivery services. Our findings have useful implications for improving the existing Safe Motherhood program in the Philippines.

Perceptions of caregivers about health and nutritional problems and feeding practices of infants: a qualitative study on exclusive breast-feeding in Kwale, Kenya.

BACKGROUND: Despite the significant positive effect of exclusive breast-feeding on child health, only 32% of children under 6 months old were exclusively breast-fed in Kenya in 2008. The aim of this study was to explore perceptions and feeding practices of caregivers of children under 6 months old with special attention to the caregivers' indigenous knowledge, perceptions about the health and nutritional problems of their infants, and care-seeking behaviors that affect feeding practices. METHODS: The study was exploratory and used an inductive approach. In all, 32 key informants, including mothers, mothers-in-law, and traditional healers, were interviewed in-depth. The number of participants in free-listing of perceived health problems of babies, in ranking of the perceived severity of these health problems, and in free-listing of food and drink given to children under 6 months old were 29, 28, and 32, respectively. Additionally, 28 babies under 6 months old were observed at home with regard to feeding practices. Data obtained using these methods were triangulated to formulate an ethnomedical explanatory model for mothers who do not practice exclusive breast-feeding. RESULTS: The informants stated that various types of food, drink, and medicine were given to infants under 6 months old. Direct observation also confirmed that 2- to 3-month-old babies were given porridge, water, juice, herbal medicine, and over-the-counter medicine. Mothers' perceptions of insufficient breast milk production and a lack of proper knowledge about the value of breast milk were identified in key informant interviews, free-listing, and ranking as important factors associating with the use of food and drink other than breast milk; in addition, perceived ill health of babies appears to be associated with suboptimal practice of exclusive breast-feeding. Caregivers used various folk and popular medicines from the drugstore, their own backyard or garden, and traditional healers so that the mother or child would not be exposed to perceived risks during the vulnerable period after birth. CONCLUSIONS: Mothers should be advised during their antenatal and postnatal care about exclusive breast-feeding. This should be done not as a single vertical message, but in relation to their concerns about the health and nutritional problems of their babies.

[Influence of nerve growth factor (NGF) on distribution of perivascular nerves in tumor neovasculatures of mouse corneal].

Angiogenesis, or new blood vessel formation, is critical for the growth and spread of tumors. The vascular tone and tissue blood flow are maintained and regulated by perivascular nerves. However, many studies have reported that tumor neovascular vessels have no innervation of perivascular nerves. We have shown that nerve growth factor (NGF) facilitated perivascular innervation and suppressed the tumor growth. From these results, we hypothesized that the neuronal regulation of blood flow toward tumors via perivascular nerves may lead suppression of the tumor growth. Therefore, the aim of this study is to investigate effect of NGF on distribution of perivascular nerves and neovessel form in tumor tissues, which were generated by mouse corneal micropocket method. A gel, which contained DU145 prostate carcinoma cells, was implanted into the mouse corneal. NGF or saline was subcutaneously administered using an osmotic mini-pump. After 1 week, the distribution of perivascular nerves in mouse corneal were immunohistochemically studied. Also, the density of neovessels (immunocytochemically stained CD31) and smooth muscles (α-smooth muscle actin; SMA) in tumor tissues was quantified by the computer-assisted image processing. Four days after implantation of tumor cells in mouse corneal, many neovessels generated from corneal limbal vessels were observed in tumor tissues. Treatment of mouse with NGF resulted in innervation of perivascular nerves around tumor neovessels, but not observed in saline-treated group. NGF treatment increased SMA-, but not CD31-, immunopositive cells. These results suggest that NGF may facilitate innervations of perivascular nerve to regulate the blood flow in tumor neovessels.

Demographic, socio-economic, behavioral and clinical factors predicting virologic failure with generic fixed-dose combination antiretroviral therapy before universal health insurance coverage in northern Thailand.

We conducted a 2-year prospective cohort study to investigate multiple aspects of factors predicting the outcome of fixed-dose combination antiretroviral (ARV) therapy with lamivudine, stavudine, and nevirapine (GPOvir) at a government referral hospital in northern Thailand. At 6 and 24 months after the initiation of GPOvir, viral load (VL) was measured to determine virologic failure (>400 RNA copies/ml) and demographic, socio-economic, behavioral and clinical data were collected. From 10 April 2002 to 31 January 2004, 409 patients participated in this study: 64/364 (17.0%) at 6 months and 55/345 (15%) at 24 months virologically failed treatment. On univariate analysis, besides ARV experience [odds ratio (OR), 3.08, 95% confidence interval (CI), 1.71 -5.57] and the frequency of delayed doses (OR, 2.97; 95% CI, 1.47-6.00), we identified one socioeconomic factor significantly associated with virologic failure: "not having child" (OR, 1.85; 95% CI, 1.03 - 3.34). Although the association with "not having child" became marginal on multivariate analysis, results of in-depth interviews and group discussions indicated that having a child was a strong motivating factor for good treatment compliance. We suggest that patients without children may need more attention. Further investigation of socio-economic factors is warranted.

Perception of bleeding as a danger sign during pregnancy, delivery, and the postpartum period in rural Nepal.

Many developing countries implement safe motherhood programs to tackle high maternal mortality rates. The approach requires recognition of the signs of emergency obstetric cases in order to facilitate immediate care seeking, followed by immediate medical care. Whether such signs are recognized in a timely manner at the community level is determined by how the community perceives health problems. We explore the local understanding of one danger sign--bleeding during pregnancy and at delivery--and the meaning attached to it. The study was conducted in the Kavrepalanchowk district of Nepal. Different qualitative methods were applied. The findings indicate that the community's perception of bleeding might be quite different from that of health professionals and that perceptions and meanings attached to bleeding vary depending on the actors in the family. They all have significant implications for what should be the focus of health education and who should be involved in promoting maternal health.

Reduced bactericidal activity and nitric oxide production in metallothionein-deficient macrophages in response to lipopolysaccharide stimulation.

This study was designed to investigate bactericidal activity of and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated peritoneal exudate macrophages (Mvarphi) from metallothionein (MT)-null mice. Control Mvarphi had a bactericidal effect on Staphylococcus aureus, but MT-null Mvarphi had significantly lower activity. NO is an important factor in the bactericidal function of Mvarphi. LPS-stimulated MT-null Mvarphi produced less NO than those of control mice. LPS-stimulated Mvarphi produce cytokines such as tumor necrosis factor (TNF)-alpha. TNF-alpha activate Mvarphi and stimulates NO production. We evaluated NO production by TNF-alpha-stimulated Mvarphi. MT-null Mvarphi produced less NO in response to TNF-alpha stimulation. Levels of expression of inducible NO synthase (iNOS) mRNA and production of iNOS protein in response to LPS stimulation were similar in MT-null and control cells, as were levels of expression of arginase, which competes in arginine metabolism with iNOS. No notable changes were found in arginine uptake or in expression of cationic amino acid transporter 2 (a major arginine transporter in Mvarphi) between control and MT-null Mvarphi. The rate of conversion of [(14)C]-l-arginine to citrulline, which is formed with NO by the action of iNOS, was much lower in MT-null Mvarphi than in control cells. These results indicate that the reduced production of NO in MT-deficient Mvarphi is due mainly to reduced activity of iNOS. Thus, MT plays important roles in bactericidal activity, NO production, and arginine metabolism in activated Mvarphi.

Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects.

OBJECTIVE: It has been demonstrated that ghrelin plays a major role in the regulation of GH secretion and food intake. These actions make ghrelin a strong candidate for the treatment of GH deficiency, anorexia and cachexia. However, only preliminary studies have been performed to assess ghrelin administration in humans. In this study, we have conducted a double-blind, randomized, placebo-controlled trial to investigate the pharmacokinetics, safety, and endocrine and appetite effects of ghrelin in young healthy volunteers. DESIGN: Eighteen male volunteers were randomly assigned into three groups of six subjects: low- and high-dose ghrelin groups, who received intravenous injections of 1 and 5 microg/kg ghrelin (acylated form) respectively, and a placebo group who were injected with mannitol instead of ghrelin. RESULTS: Acylated ghrelin disappeared more rapidly from plasma than total ghrelin, with elimination half life (t(1/2)) of 9-13 and 27-31 min respectively. The number of subjects that experienced adverse effects did not significantly differ among the three groups, and all adverse effects were transient and well tolerated. Both the low and high doses of ghrelin strongly stimulated GH release (peak plasma concentration (C(max,0-90 min)): 124.2+/-63.9 and 153.2+/-52.2 ng/ml for 1 and 5 microg/kg ghrelin respectively). Slight alterations of blood glucose and insulin levels after the injection were observed. Although not statistically significant, ghrelin administration tended to increase hunger sensation in a dose-dependent manner. CONCLUSIONS: These results suggest that ghrelin is safe, and that clinical trials may be started to assess the usefulness of ghrelin for the treatment of disorders related to GH secretion and appetite.

Metallothionein modulates lipopolysaccharide-stimulated tumour necrosis factor expression in mouse peritoneal macrophages.

Metallothionein (MT) is a low-molecular-mass, cysteine-rich metal binding protein thought to be involved in the detoxification of heavy metals and scavenging of free radicals. MT is directly induced not only by heavy metals, but also by hormones and cytokines. The present study, which uses mice with genetic deletions of the MT proteins (MT(-/-) mice), was designed to evaluate the effects of MT on the expression of pro-inflammatory cytokines in macrophages. We found that the production of tumour necrosis factor (TNF) induced by lipopolysaccharide (LPS) in peritoneal macrophages is up-regulated by MT via the modulation of nuclear factor kappaB (NF-kappaB) activity. This conclusion is supported by the following observations: (1) LPS stimulated the secretion of less TNF activity from MT(-/-) peritoneal exudate macrophages (PEMs) than from wild-type controls (MT(+/+) mice) without a difference in the pattern of kinetics; (2) LPS-stimulated expression of TNF-alpha mRNA was decreased in MT(-/-) PEMs; (3) LPS-stimulated activation of NF-kappaB was decreased in MT(-/-) PEMs; and (4) production of TNF in PEMs of MT(-/-) mice after LPS treatment in vivo was decreased (compared with MT(+/+) PEMs). Expression of other inflammatory cytokines, interleukin (IL)-1alpha and IL-6 mRNA, which were modulated by NF-kappaB, were also down-regulated in MT(-/-) PEMs. Thus MT plays a key role in the LPS-induced activation of PEMs via the modulation of NF-kappaB activity.