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1.  Receiving an Alcohol Enquiry from a Physician in Routine Health Care in Sweden: A Population-Based Study of Gender Differences and Predictors 
Research has shown that the provision of brief interventions in the health care system is effective for reducing hazardous drinking. Using a telephone-administered questionnaire, this study provides a population-based investigation on the extent to which physicians address patients’ alcohol habits in the Swedish health care system, whether there are gender differences in the extent to which patients receive questions about alcohol, and predictors for receiving such questions. Data were obtained from monthly telephone surveys with around 72,000 people in 2006–2009. Having received an alcohol enquiry was defined as having been asked about one’s drinking habits by a physician in any health care visit in the last 12 months. Fourteen percent of the total population had received an alcohol enquiry, but there were considerable gender differences: for hazardous drinkers, 13% of the women and 17% of the men had received an alcohol enquiry; among those with sensible alcohol consumption, 10% of women and 15% of men had received an alcohol enquiry. Patients were more likely to have received an alcohol enquiry if they had self-reported alcohol-related problems, were hazardous drinkers and/or daily smokers. Some of the alcohol enquiry predictors differed by gender; social class was an important predictor for women but not for men.
doi:10.3390/ijerph8051296
PMCID: PMC3108110  PMID: 21655120
alcohol enquiry; health care; gender; hazardous drinking; alcohol-related problems; social class
2.  Interpretation of England and Wales cancer mortality data: the effect of enquiries to certifiers for further information. 
British Journal of Cancer  1989;59(5):787-791.
For some death certificates in England and Wales the cause information coded and published in national data is not that initially submitted by the certifier, but instead derives from a subsequent enquiry to the certifier for further information. These enquiries can lead to substantial artefacts in secular mortality data, and also to substantial non-comparability between mortality data for special study groups, such as subjects in cohort studies, and published mortality data. A description of current enquiry policy relevant to cancers, and changes in this policy over recent years is given to aid interpretation of mortality data. The effects on secular data of changes in enquiry policy are illustrated. At 4-digit level of the ICD, changes in enquiry policy can alter published mortality rates by several hundred per cent. At 3-digit level the greatest effects of enquiries at present are to increase the number of deaths coded to cancer of the eye by 35% and cancer of the body of the uterus by 31%; cancers of the thymus, heart and mediastinum are increased by 18%, and pleural cancer by 17%, while decreases of more than 10% are caused for several 'other' and 'unspecified' rubrics, and a decrease of 6% for deaths coded to melanoma.
PMCID: PMC2247208  PMID: 2736214
3.  An Integrated Imaging Approach to the Study of Oxidative Stress Generation by Mitochondrial Dysfunction in Living Cells 
Environmental Health Perspectives  2010;118(7):902-908.
Background
The mechanisms of action of many environmental agents commonly involve oxidative stress resulting from mitochondrial dysfunction. Zinc is a common environmental metallic contaminant that has been implicated in a variety of oxidant-dependent toxicological responses. Unlike ions of other transition metals such as iron, copper, and vanadium, Zn2+ does not generate reactive oxygen species (ROS) through redox cycling.
Objective
To characterize the role of oxidative stress in zinc-induced toxicity.
Methods
We used an integrated imaging approach that employs the hydrogen peroxide (H2O2)-specific fluorophore Peroxy Green 1 (PG1), the mitochondrial potential sensor 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and the mitochondria-targeted form of the redox-sensitive genetically encoded fluorophore MTroGFP1 in living cells.
Results
Zinc treatment in the presence of the Zn2+ ionophore pyrithione of A431 skin carcinoma cells preloaded with the H2O2-specific indicator PG1 resulted in a significant increase in H2O2 production that could be significantly inhibited with the mitochondrial inhibitor carbonyl cyanide 3-chlorophenylhydrazone. Mitochondria were further implicated as the source of zinc-induced H2O2 formation by the observation that exposure to zinc caused a loss of mitochondrial membrane potential. Using MTroGFP1, we showed that zinc exposure of A431 cells induces a rapid loss of reducing redox potential in mitochondria. We also demonstrated that zinc exposure results in rapid swelling of mitochondria isolated from mouse hearts.
Conclusion
Taken together, these findings show a disruption of mitochondrial integrity, H2O2 formation, and a shift toward positive redox potential in cells exposed to zinc. These data demonstrate the utility of real-time, live-cell imaging to study the role of oxidative stress in toxicological responses.
doi:10.1289/ehp.0901811
PMCID: PMC2920907  PMID: 20413366
biosensors; confocal microscopy; hydrogen peroxide; mitochondrial dysfunction; oxidative stress; real-time imaging; ROS
4.  Suicide-related discussions with depressed primary care patients in the USA: gender and quality gaps. A mixed methods analysis 
BMJ Open  2011;1(2):e000198.
Objective
To characterise suicide-risk discussions in depressed primary-care patients.
Design
Secondary analysis of recordings and self reports by physicians and patients. Descriptive statistics of depression and suicide-related discussion, with qualitative extraction of disclosure, enquiry and physician response.
Setting
12 primary-care clinics between July 2003 and March 2005.
Participants
48 primary-care physicians and 1776 adult patients.
Measures
Presence of depression or suicide-related discussions during the encounter; patient and physician demographics; depression symptom severity and suicide ideation as measured by the Patient Health Questionnaire (PHQ9); physician's decision-making style as measured by the Medical Outcomes Study Participatory Decision-Making Scale; support for autonomy as measured by the Health Care Climate Questionnaire; trust in their physician as measured by the Primary Care Assessment Survey; physician response to suicide-related enquiry or disclosure.
Results
Of the 1776 encounters, 128 involved patients scoring >14 on the PHQ9. These patients were seen by 43 of the 48 physicians. Suicide ideation was endorsed by 59% (n=75). Depression was discussed in 52% of the encounters (n=66). Suicide-related discussion occurred in only 11% (n=13) of encounters. 92% (n=12) of the suicide discussions occurred with patients scoring <2 on PHQ9 item 9. Suicide was discussed in only one encounter with a male. Variation in elicitation and response styles demonstrated preferred and discouraged interviewing strategies.
Conclusions
Suicide ideation is present in a significant proportion of depressed primary care patients but rarely discussed. Men, who carry the highest risk for suicide, are unlikely to disclose their ideation or be asked about it. Patient-centred communication and positive healthcare climate do not appear to increase the likelihood of suicide related discussion. Physicians should be encouraged to ask about suicide ideation in their depressed patients and, when disclosure occurs, facilitate discussion and develop targeted treatment plans.
Article summary
Article focus
Determine frequency of suicide-related discussions in routine primary-care encounters with depressed patients along with demographic predictors.
Identify process variables that may or may not influence the likelihood that suicide will be discussed in primary care.
Analyse interview style related to enquiring about suicide and responding to patient responses to enquiry as well as unsolicited disclosure.
Key messages
Suicide is addressed in a small minority of encounters with depressed patients in primary care.
Suicide is rarely discussed with depressed male patients who are at high risk for suicide.
Physician enquiries related to suicide are often made with patients who have the lowest levels of ideation, and the enquiries themselves are often biased to elicit a denial of ideation.
Strengths and limitations of this study
The study involved a large number of primary care physicians and patients representing real-world patient encounters.
It is unknown if the topic of suicide had been discussed in previous encounters and how such discussion influenced the present encounter.
We were unable to identify significant predictors of suicide-related discussion, yet we were able to demonstrate that some likely candidates such as participatory decision-making style and trust were not sufficient.
doi:10.1136/bmjopen-2011-000198
PMCID: PMC3191598  PMID: 22021884
5.  CICATRIZATION OF WOUNDS  
Sodium stearate has no effect upon the bacteriological condition of a wound, but the addition of 4 parts per 1,000 of chloramine-T renders it antiseptic. Experiment I enabled us to compare the action of sodium stearate alone with that of sodium stearate containing 4 parts per 1,000 of chloramine-T. Wounds which had been previously sterilized could be maintained in an aseptic condition by 4 parts per 1,000 of chloramine-T, although in some cases reinfection occurred (Experiments 2, 3, and 5). For this reason the concentration of chloramine-T was increased. Surface wounds, deep-seated wounds, and osseous cavities, which had previously been either completely or almost completely sterilized, could be maintained for days and even weeks in a condition of surgical asepsis by the use of a paste containing 7 and 10 parts per 1,000 of chloramine-T. Experiments 7, 8, 9, 10, and 12 are examples of this. Slightly infected wounds (Experiments 9, II, and 12) were sterilized in the same manner. Next, it was attempted to sterilize wounds which were suppurating and more or less infected, and in some cases accompanied by fracture. This attempt was probably successful because the wounds used for the experiments showed but slight quantities of secretions and only a shallow layer of necrotic tissue. It is useless to attempt to sterilize severely infected wounds with a paste, for the volume of chloramine-T that can be applied is too limited. A large volume of an active substance is required to sterilize a wound which secretes great quantities of pus, for owing, on the one hand, to the dilution of this substance with the secretions, and, on the other, to its combination with the proteins contained in the pus, the concentration of the antiseptic is rapidly diminished. For these reasons it is essential that the antiseptic solution should be constantly renewed, so that the concentration may be sufficiently strong to effect the destruction of the bacteria. Therefore, the chloramine-T paste cannot sterilize a severely infected wound. The concentration of the active substance contained in a paste must at the same time be sufficiently weak to be innocuous to the tissues. We have seen that it should not exceed 15 parts per 1,000. Thus, it is evident that if the secretions from the wounds are abundant, the substance could exert its action upon the microorganisms for the space of only a few hours. For this reason the chloramine paste should only be applied under the conditions specified in our experiments; that is, in connection with moderately infected wounds which have been carefully washed with sodium oleate, and possess but slight quantities of secretion. Under these conditions, the chloramine paste effects the complete disappearance of the bacteria and maintains the sterility thus secured for as long a time as may be wished. If the technique followed in the dressing is not exactly as above described, reinfection will occur. If applied in this manner the chloramine paste is not injurious to the tissues, for the cicatrization curves of the wounds thus treated show but slight modification from the calculated curves. Chloramine paste makes it possible, therefore, to keep wounds sufficiently free from microorganisms so that the effect of substances which are believed to influence cicatrization can be studied.
PMCID: PMC2125525  PMID: 19868140
6.  Inhibition of collagen-induced platelet aggregation by normal plasma 
Journal of Clinical Investigation  1971;50(10):2168-2175.
Normal plasma has been found to inhibit the platelet aggregation-inducing effect of collagen in a time consuming reaction independent of temperature. Collagen treated with serum and washed has reduced reactivity which can be restored to normal by treatment with 1.5 M sodium chloride. On the basis of this result, it is suggested that inhibition results from adsorption to collagen of a plasma component. The inhibitory plasma component is destroyed at 56°C, is unstable below pH 7, and migrates with the alpha globulins on starch block electrophoresis at pH 8.6. On the basis of ultrafiltration and sucrose density gradient ultracentrifugation studies, a molecular weight in the range of 330,000 is suggested and there may be an additional component of considerably greater size. Partial purification can be achieved by ion exchange chromatography. The purified fraction was completely inactivated by incubation with trypsin. Partially purified fractions inhibit cationic platelet aggregators such as collagen, polylysine, and hexadimethrine but do not affect anionic aggregators such as succinylated collagen and sodium stearate. Normal plasma and serum inhibit succinylated collagen and stearate. Stearate is inhibited by crystalline albumin and Cohn fraction IV-4. It is suggested that plasma proteins may regulate platelet adhesion to collagen and other vessel wall materials.
Images
PMCID: PMC292151  PMID: 4107268
7.  Prevention of carcinogenesis and inhibition of breast cancer tumor burden by dietary stearate 
Carcinogenesis  2011;32(8):1251-1258.
Previous studies have shown that stearate (C18:0), a dietary long-chain saturated fatty acid, inhibits breast cancer cell neoplastic progression; however, little is known about the mechanism modulating these processes. We demonstrate that stearate, at physiological concentrations, inhibits cell cycle progression in human breast cancer cells at both the G1 and G2 phases. Stearate also increases cell cycle inhibitor p21CIP1/WAF1 and p27KIP1 levels and concomitantly decreases cyclin-dependent kinase 2 (Cdk2) phosphorylation. Our data also show that stearate induces Ras– guanosine triphosphate formation and causes increased phosphorylation of extracellular signal-regulated kinase (pERK). The MEK1 inhibitor, PD98059, reversed stearate-induced p21CIP1/WAF1 upregulation, but only partially restored stearate-induced dephosphorylation of Cdk2. The Ras/mitogen-activated protein kinase/ERK pathway has been linked to cell cycle regulation but generally in a positive way. Interestingly, we found that stearate inhibits both Rho activation and expression in vitro. In addition, constitutively active RhoC reversed stearate-induced upregulation of p27KIP1, providing further evidence of Rho involvement. To test the effect of stearate in vivo, we used the N-Nitroso-N-methylurea rat breast cancer carcinogen model. We found that dietary stearate reduces the incidence of carcinogen-induced mammary cancer and reduces tumor burden. Importantly, mammary tumor cells from rats on a stearate diet had reduced expression of RhoA and B as well as total Rho compared with a low-fat diet. Overall, these data indicate that stearate inhibits breast cancer cell proliferation by inhibiting key check points in the cell cycle as well as Rho expression in vitro and in vivo and inhibits tumor burden and carcinogen-induced mammary cancer in vivo.
doi:10.1093/carcin/bgr092
PMCID: PMC3149204  PMID: 21586513
8.  Effect of Supplementation with Zinc and Other Micronutrients on Malaria in Tanzanian Children: A Randomised Trial 
PLoS Medicine  2011;8(11):e1001125.
Hans Verhoef and colleagues report findings from a randomized trial conducted among Tanzanian children at high risk for malaria. Children in the trial received either daily oral supplementation with either zinc alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. The investigators did not find evidence from this study that zinc or multi-nutrients protected against malaria episodes.
Background
It is uncertain to what extent oral supplementation with zinc can reduce episodes of malaria in endemic areas. Protection may depend on other nutrients. We measured the effect of supplementation with zinc and other nutrients on malaria rates.
Methods and Findings
In a 2×2 factorial trial, 612 rural Tanzanian children aged 6–60 months in an area with intense malaria transmission and with height-for-age z-score≤−1.5 SD were randomized to receive daily oral supplementation with either zinc alone (10 mg), multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Intervention group was indicated by colour code, but neither participants, researchers, nor field staff knew who received what intervention. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. The primary outcome, an episode of malaria, was assessed among children reported sick at a primary care clinic, and pre-defined as current Plasmodium infection with an inflammatory response, shown by axillary temperature ≥37.5°C or whole blood C-reactive protein concentration ≥8 mg/L. Nutritional indicators were assessed at baseline and at 251 days (median; 95% reference range: 191–296 days). In the primary intention-to-treat analysis, we adjusted for pre-specified baseline factors, using Cox regression models that accounted for multiple episodes per child. 592 children completed the study. The primary analysis included 1,572 malaria episodes during 526 child-years of observation (median follow-up: 331 days). Malaria incidence in groups receiving zinc, multi-nutrients without zinc, multi-nutrients with zinc and placebo was 2.89/child-year, 2.95/child-year, 3.26/child-year, and 2.87/child-year, respectively. There was no evidence that multi-nutrients influenced the effect of zinc (or vice versa). Neither zinc nor multi-nutrients influenced malaria rates (marginal analysis; adjusted HR, 95% CI: 1.04, 0.93–1.18 and 1.10, 0.97–1.24 respectively). The prevalence of zinc deficiency (plasma zinc concentration <9.9 µmol/L) was high at baseline (67% overall; 60% in those without inflammation) and strongly reduced by zinc supplementation.
Conclusions
We found no evidence from this trial that zinc supplementation protected against malaria.
Trial Registration
ClinicalTrials.gov NCT00623857
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Malaria is a serious global public-health problem. Half of the world's population is at risk of this parasitic disease, which kills a million people (mainly children living in sub-Saharan Africa) every year. Malaria is transmitted to people through the bites of infected night-flying mosquitoes. Soon after entering the human body, the parasite begins to replicate in red blood cells, bursting out every 2–3 days and infecting more red blood cells. The presence of the parasite in the blood stream (parasitemia) causes malaria's characteristic recurring fever and can cause life-threatening organ damage and anemia (insufficient quantity of red blood cells). Malaria transmission can be reduced by using insecticide sprays to control the mosquitoes that spread the parasite and by avoiding mosquito bites by sleeping under insecticide-treated bed nets. Effective treatment with antimalarial drugs can also reduce malaria transmission.
Why Was This Study Done?
One reason why malaria kills so many children in Africa is poverty. Many children in Africa are malnourished, and malnutrition—in particular, insufficient micronutrients in the diet—impairs the immune system, which increases the frequency and severity of many childhood diseases. Micronutrients are vitamins and minerals that everyone needs in small quantities for good health. Zinc is one of the micronutrients that helps to maintain a healthy immune system, but zinc deficiency is very common among African children. Zinc supplementation has been shown to reduce the burden of diarrhea in developing countries, so might it also reduce the burden of malaria? Unfortunately, the existing evidence is confusing—some trials show that zinc supplementation protects against malaria but others show no evidence of protection. One possibility for these conflicting results could be that zinc supplementation alone is not sufficient—supplementation with other micronutrients might be needed for zinc to have an effect. In this randomized trial (a study that compares the effects of different interventions in groups that initially are similar in all characteristics except for intervention), the researchers investigate the effect of supplementation with zinc alone and in combination with other micronutrients on the rate of uncomplicated (mild) malaria among children living in Tanzania.
What Did the Researchers Do and Find?
The researchers enrolled 612 children aged 6–60 months who were living in a rural area of Tanzania with intense malaria transmission and randomly assigned them to receive daily oral supplements containing zinc alone, multi-nutrients (including iron) without zinc, multi-nutrients with zinc, or a placebo (no micronutrients). Nutritional indicators (including zinc concentrations in blood plasma) were assessed at baseline and 6–10 months after starting the intervention. During the study period, there were 1,572 malaria episodes. The incidence of malaria in all four intervention groups was very similar (about three episodes per child-year), and there was no evidence that multi-nutrients influenced the effect of zinc (or vice versa). Moreover, none of the supplements had any effect on malaria rates when compared to the placebo, even though the occurrence of zinc deficiency was strongly reduced by zinc supplementation. In a secondary analysis in which they analyzed their data by iron status at baseline, the researchers found that multi-nutrient supplementation increased the overall number of malaria episodes in children with iron deficiency by 41%, whereas multi-nutrient supplementation had no effect on the number of malaria episodes among children who were iron-replete at baseline.
What Do These Findings Mean?
In this study, the researchers found no evidence that zinc supplementation protected against malaria among young children living in Tanzania when given alone or in combination with other multi-nutrients. However, the researchers did find some evidence that multi-nutrient supplementation may increase the risk of malaria in children with iron deficiency. Because this finding came out of a secondary analysis of the data, it needs to be confirmed in a trial specifically designed to assess the effect of multi-nutrient supplements on malaria risk in iron-deficient children. Nevertheless, it is a potentially worrying result because, on the basis of evidence from a single study, the World Health Organization currently recommends that regular iron supplements be given to iron-deficient children in settings where there is adequate access to anti-malarial treatment. This recommendation should be reconsidered, suggest the researchers, and the safety of multi-nutrient mixes that contain iron and that are dispensed in countries affected by malaria should also be carefully evaluated.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001125.
Information is available from the World Health Organization on malaria (in several languages), on micronutrients, and on zinc deficiency; the 2010 World Malaria Report provides details of the current global malaria situation
The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish), including a selection of personal stories about malaria
Information is available from the Roll Back Malaria Partnership on the global control of malaria and on malaria in Africa
The Malaria Centre at the UK London School of Hygiene & Tropical Medicine develops tools, techniques, and knowledge about malaria, and has a strong emphasis on teaching, training, and translating research outcomes into practice
The Micronutrient Initiative, the Global Alliance for Improved Nutrition, and the Flour Fortification Initiative are not-for-profit organizations dedicated to ensuring that people in developing countries get the minerals and vitamins they need to survive and thrive
The International Zinc Nutrition Consultative Group (iZiNCG) is a non-profit organization that aims to promote and assist efforts to reduce zinc deficiency worldwide, through advocacy efforts, education, and technical assistance
MedlinePlus provides links to additional information on malaria (in English and Spanish)
doi:10.1371/journal.pmed.1001125
PMCID: PMC3222646  PMID: 22131908
9.  Modification of composition of a nanoemulsion with different cholesteryl ester molecular species: Effects on stability, peroxidation, and cell uptake 
Purpose:
Use of lipid nanoemulsions as carriers of drugs for therapeutic or diagnostic purposes has been increasingly studied. Here, it was tested whether modifications of core particle constitution could affect the characteristics and biologic properties of lipid nanoemulsions.
Methods:
Three nanoemulsions were prepared using cholesteryl oleate, cholesteryl stearate, or cholesteryl linoleate as main core constituents. Particle size, stability, pH, peroxidation of the nanoemulsions, and cell survival and uptake by different cell lines were evaluated.
Results:
It was shown that cholesteryl stearate nanoemulsions had the greatest particle size and all three nanoemulsions were stable during the 237-day observation period. The pH of the three nanoemulsion preparations tended to decrease over time, but the decrease in pH of cholesteryl stearate was smaller than that of cholesteryl oleate and cholesteryl linoleate. Lipoperoxidation was greater in cholesteryl linoleate than in cholesteryl oleate and cholesteryl stearate. After four hours’ incubation of human umbilical vein endothelial cells (HUVEC) with nanoemulsions, peroxidation was minimal in the presence of cholesteryl oleate and more pronounced with cholesteryl linoleate and cholesteryl stearate. In contrast, macrophage incubates showed the highest peroxidation rates with cholesteryl oleate. Cholesteryl linoleate induced the highest cell peroxidation rates, except in macrophages. Uptake of cholesteryl oleate nanoemulsion by HUVEC and fibroblasts was greater than that of cholesteryl linoleate and cholesteryl stearate. Uptake of the three nanoemulsions by monocytes was equal. Uptake of cholesteryl oleate and cholesteryl linoleate by macrophages was negligible, but macrophage uptake of cholesteryl stearate was higher. In H292 tumor cells, cholesteryl oleate showed the highest uptakes. HUVEC showed higher survival rates when incubated with cholesteryl stearate and smaller survival with cholesteryl linoleate. H292 survival was greater with cholesteryl stearate.
Conclusion:
Although all three nanoemulsion types were stable for a long period, considerable differences were observed in size, oxidation status, and cell survival and nanoemulsion uptake in all tested cell lines. Those differences may be helpful in protocol planning and interpretation of data from experiments with lipid nanoemulsions.
PMCID: PMC2948947  PMID: 20957219
emulsions; cholesterol; drug vehicles; lipoprotein receptors; solid lipid nanoparticles
10.  Degradability Enhancement of Poly(Lactic Acid) by Stearate-Zn3Al LDH Nanolayers 
Recent environmental problems and societal concerns associated with the disposal of petroleum based plastics throughout the world have triggered renewed efforts to develop new biodegradable products compatible with our environment. This article describes the preparation, characterization and biodegradation study of poly(lactic acid)/layered double hydroxide (PLA/LDH) nanocomposites from PLA and stearate-Zn3Al LDH. A solution casting method was used to prepare PLA/stearate-Zn3Al LDH nanocomposites. The anionic clay Zn3Al LDH was firstly prepared by co-precipitation method from a nitrate salt solution at pH 7.0 and then modified by stearate anions through an ion exchange reaction. This modification increased the basal spacing of the synthetic clay from 8.83 Å to 40.10 Å. The morphology and properties of the prepared PLA/stearate-Zn3Al LDH nanocomposites were studied by X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), thermogravimetric analysis (TGA), tensile tests as well as biodegradation studies. From the XRD analysis and TEM observation, the stearate-Zn3Al LDH lost its ordered stacking-structure and was greatly exfoliated in the PLA matrix. Tensile test results of PLA/stearate-Zn3Al LDH nanocomposites showed that the presence of around 1.0–3.0 wt % of the stearate-Zn3Al LDH in the PLA drastically improved its elongation at break. The biodegradation studies demonstrated a significant biodegradation rate improvement of PLA in the presence of stearate-Zn3Al LDH nanolayers. This effect can be caused by the catalytic role of the stearate groups in the biodegradation mechanism leading to much faster disintegration of nanocomposites than pure PLA.
doi:10.3390/ijms13077938
PMCID: PMC3430213  PMID: 22942682
poly(lactic acid); nanocomposites; layered double hydroxide; biodegradability enhancement; flexibility improvement
11.  What effects has the cataract surgery on the development and progression of Age-Related Macular Degeneration (AMD)? 
Background
The cataract (Cataracta senilis) is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology – can be seen as routine surgery. The age related macular degeneration (AMD) is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing number of patients will suffer from cataract and AMD at the same time. This coincidence leads to a greater interest in the question of a mutual influence of both diseases, respectively their therapies, on each other.
Objectives
The aim of this report was the evaluation of the medical and health economic effects of cataract operations on the development and progression of an age related macular degeneration (AMD). It was differentiated between first manifestations of AMD, progression of early stages of AMD and influence on further impairment in late stages of AMD.
Methods
The relevant publications for this report were identified by DIMDI via structured database enquiry as well as common, self-made enquiry and were evaluated, based on the criteria of evidence based medicine. The present report included German and English literature published since 1983.
Results
The database enquiry generated a record of 2769 issue-related publications. Eight medical publications were eligible for analysis in the course of the present HTA report. No relevant studies on health economical, ethical, social or legal issues could be included. Three epidemiological cohort studies provided some evidence for a promoting influence of cataract extractions on the progression of early types of AMD. Two of the epidemiological studies assessed the risk of first manifestation of AMD after cataract extraction. Both came up with up with increased incidences that did not reach statistical significance despite a large number of participants. Only one out of two clinical studies looked at further impairment in late stages of AMD and could not find an interrelation with cataract extraction. Thus the available evidence was not sufficient to come to a conclusion on the contribution of cataract extractions to the first manifestation of AMD and to the further impairment in late stages.
Discussion
The presentation of the evaluated literature made clear that only a small number of publications dealt with the development of age related macula degeneration in consequence of a cataract extraction. The overall scientific level of evidence of these articles was not very high. Therefore it was not possible to obtain a well-defined conclusion on the effect of a cataract extraction on the development or progression of an age related macula degeneration.
Conclusion
Additional well conducted clinical trials, that offer a sufficient number of patients, length of study period and adequate control for confounding variables like age and severity of cataract, are urgently needed. Health economic, ethical, social and legal aspect of the problem could and should be investigated after clarification of the mentioned medical issues.
PMCID: PMC3011353  PMID: 21289972
12.  Review, discussion, and summary: toxicology. 
The research presented in the toxicology session of the Symposium on the Health Effects of Acid Aerosols significantly advances our understanding of the health effects of acid aerosols and clearly illustrates the importance of animal inhalation toxicology to risk assessment. The description of the effects of acid on airway mucus buffering capacity and viscosity helps explain some of the mechanisms responsible for the effects of sulfuric acid on mucociliary clearance and pulmonary function observed in man and animals. Several of the papers illustrate that other pollutants interact with sulfuric acid (H2SO4), causing concern about exposure risks and helping in elucidating the effects observed in epidemiology studies that have not yet been duplicated in a laboratory. For example, H2SO4 absorbed in zinc oxide (ZnO) particles appears to be about a log more potent than H2SO4 alone in causing pulmonary function decrements. Low levels of H2SO4 and O3 were found to be synergistic in increasing collagen synthesis, implying a risk in development of lung fibrosis. More complex mixtures containing H2SO4 cause a variety of interactions, depending upon the end points examined and the chemistry of the mixture. Other reports indicate that dose rate and length of exposure issues are critical to toxicological outcomes. Animal data on mucociliary clearance, which parallels that of human data, was extended to show that concentration of exposure was more important than time of exposure in eliciting a response, although time played a significant role. A recent chronic study showed that H2SO4 caused effects that also can occur in the development of chronic bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)
PMCID: PMC1567562  PMID: 2707198
13.  X-ray diffraction studies of the composition of gallstones from English and Australian patients 
Gut  1969;10(8):681-683.
The crystalline composition of two collections of gallstones from patients in England and Australia have been determined by the x-ray powder diffraction technique. Twelve substances have been identified including a form of cholesterol which hitherto has not been reported. The weighted percentage composition averaged over each collection shows that cholesterol is the major constituent of the Australian stones and cholesterol and cholesterol monohydrate the major constituents of the English calculi. The cholesterol is possibly a decomposition product of the monohydrate. The calcium carbonates—calcite, aragonite, and vaterite—constitute most of the remainder of the calculi. Although their percentage composition is much smaller than that of the cholesterols, they are nevertheless present in a high proportion of stones. Small traces of apatite, whitlockite, sodium chloride, calcium stearate and palmitic acid (or other long-chain compounds having closely related spacings) have been found. Small spheroids scattered throughout some stones appear to be mainly calcium stearate, although the total quantity available is too small and too impure for a definite identification.
PMCID: PMC1552904  PMID: 5822141
14.  Measurement of de novo hepatic lipogenesis in humans using stable isotopes. 
Journal of Clinical Investigation  1991;87(5):1841-1852.
Direct measurement of de novo lipogenesis has not previously been possible in humans. We measured de novo hepatic lipogenesis in normal men by means of stable isotopes and by combining the acetylated-xenobiotic probe technique with mass isotopomer analysis of secreted very low density lipoprotein-fatty acids (VLDL-FA). Sulfamethoxazole (SMX) was administered with [13C]acetate during an overnight fast followed by refeeding with intravenous glucose (7-10 mg/kg of weight per min), oral Ensure (7-10 mg of carbohydrate/kg of weight per min), or a high-carbohydrate mixed-meal breakfast (3.5 g of carbohydrate/kg of weight). Respiratory quotients remained less than 1.0. High-performance liquid chromatography/mass spectrometry-determined enrichments in SMX-acetate attained stable plateau values, and hepatic acetyl-coenzyme A (CoA) dilution rate did not increase with refeeding (approximately 0.024 mmol/kg per min). The fraction of VLDL-palmitate derived from de novo lipogenesis was only 0.91 +/- 0.27% (fasted) and 1.64-1.97% (fed). For stearate, this was 0.37 +/- 0.08% and 0.47-0.64%. Precursor enrichments predicted from isotopomer ratios were close to measured SMX-acetate enrichments, indicating that SMX-acetate samples the true lipogenic acetyl-CoA pool. Stearate synthesis was less than palmitate and the two did not move in parallel. Estimated total VLDL-FA synthesis is less than 500 mg/day. Thus, de novo hepatic lipogenesis is a quantitatively minor pathway, consistent with gas exchange estimates; fatty acid futile cycling (oxidation/resynthesis) is not thermogenically significant; and synthesis rates of different nonessential fatty acids by human liver are not identical in nonoverfed normal men. The contribution and regulation of de novo lipogenesis in other settings can be studied using this technique.
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PMCID: PMC295308  PMID: 2022750
15.  Chronic alcoholic skeletal muscle myopathy: a clinical, histological and biochemical assessment of muscle lipid. 
Journal of Clinical Pathology  1983;36(7):778-784.
Muscle biopsy samples were analysed from five control subjects, four patients with mild to moderate fibre atrophy and four patients with severe atrophy. Patchy increase in lipid was noted with oil red O staining but there was no consistent association of lipid with selective fibre types. Ultrastructural studies demonstrated lipid droplets both subjacent to the sarcolemma and between fibrils. Quantitative analysis showed that the increased lipid was solely due to excess triglyceride. GLC analysis of free and esterified acids was performed. The profiles were essentially similar for the phospholipid and free fatty acid fractions. The triglyceride fraction showed a decrease of myristate, stearate and linoleate with an increase in oleate and arachidate in the alcoholic tissue compared with control. The cholesteryl ester fraction showed an increase in palmitate with a decrease in stearate and oleate in the alcoholic muscle. The accumulation of lipid correlated with mean daily alcohol consumption but not with degree of atrophy suggesting that the two processes probably had different pathogenic mechanisms.
Images
PMCID: PMC498387  PMID: 6863570
16.  High levels of dietary stearate promote adiposity and deteriorate hepatic insulin sensitivity 
Background
Relatively little is known about the role of specific saturated fatty acids in the development of high fat diet induced obesity and insulin resistance. Here, we have studied the effect of stearate in high fat diets (45% energy as fat) on whole body energy metabolism and tissue specific insulin sensitivity.
Methods
C57Bl/6 mice were fed a low stearate diet based on palm oil or one of two stearate rich diets, one diet based on lard and one diet based on palm oil supplemented with tristearin (to the stearate level of the lard based diet), for a period of 5 weeks. Ad libitum fed Oxidative metabolism was assessed by indirect calorimetry at week 5. Changes in body mass and composition was assessed by DEXA scan analysis. Tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analysis and Western blot at the end of week 5.
Results
Indirect calorimetry analysis revealed that high levels of dietary stearate resulted in lower caloric energy expenditure characterized by lower oxidation of fatty acids. In agreement with this metabolic phenotype, mice on the stearate rich diets gained more adipose tissue mass. Whole body and tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and analysis of insulin induced PKBser473 phosphorylation. Whole body insulin sensitivity was decreased by all high fat diets. However, while insulin-stimulated glucose uptake by peripheral tissues was impaired by all high fat diets, hepatic insulin sensitivity was affected only by the stearate rich diets. This tissue-specific pattern of reduced insulin sensitivity was confirmed by similar impairment in insulin-induced phosphorylation of PKBser473 in both liver and skeletal muscle.
Conclusion
In C57Bl/6 mice, 5 weeks of a high fat diet rich in stearate induces a metabolic state favoring low oxidative metabolism, increased adiposity and whole body insulin resistance characterized by severe hepatic insulin resistance. These results indicate that dietary fatty acid composition per sé rather than dietary fat content determines insulin sensitivity in liver of high fat fed C57Bl/6 mice.
doi:10.1186/1743-7075-7-24
PMCID: PMC2852377  PMID: 20346174
17.  Dietary Stearate Reduces Human Breast Cancer Metastasis Burden in Athymic Nude Mice 
Stearate is an 18-carbon saturated fatty acid found in many foods in the western diet, including beef and chocolate. Stearate has been shown to have anti-cancer properties during early stages of neoplastic progression. However, previous studies have not investigated the effect of dietary stearate on breast cancer metastasis. In this study, we present evidence that exogenously supplied dietary stearate dramatically reduces the size of tumors that formed from injected human breast cancer cells within the mammary fat pads of athymic nude mice by approximately 50% and partially inhibits breast cancer cell metastasis burden in the lungs in this mouse model system. This metastatic inhibition appears to be independent of primary tumor size, as stearate fed animals that had primary tumors comparable in size to littermates fed either a safflower oil enriched diet or a low fat diet had reduced lung metastasis. Also stearate fed mice sub-groups had different primary tumor sizes but no difference in metastasis. This anti-metastasis effect may be due, at least in part, to the ability of stearate to induce apoptosis in these human breast cancer cells. Overall, this study suggests the possibility of dietary manipulation with selected long-chain saturated fatty acids such as stearate as a potential adjuvant therapeutic strategy for breast cancer patients wishing to maximize the suppression of metastatic disease.
doi:10.1007/s10585-009-9239-x
PMCID: PMC2946234  PMID: 19267249
Breast cancer; dietary fat; metastasis; linoleic acid; stearic acid; stearate
18.  The spindle pole body of Schizosaccharomyces pombe enters and leaves the nuclear envelope as the cell cycle proceeds. 
Molecular Biology of the Cell  1997;8(8):1461-1479.
The cycle of spindle pole body (SPB) duplication, differentiation, and segregation in Schizosaccharomyces pombe is different from that in some other yeasts. Like the centrosome of vertebrate cells, the SPB of S. pombe spends most of interphase in the cytoplasm, immediately next to the nuclear envelope. Some gamma-tubulin is localized on the SPB, suggesting that it plays a role in the organization of interphase microtubules (MTs), and serial sections demonstrate that some interphase MTs end on or very near to the SPB. gamma-Tubulin is also found on osmiophilic material that lies near the inner surface of the nuclear envelope, immediately adjacent to the SPB, even though there are no MTs in the interphase nucleus. Apparently, the MT initiation activities of gamma-tubulin in S. pombe are regulated. The SPB duplicates in the cytoplasm during late G2 phase, and the two resulting structures are connected by a darkly staining bridge until the mitotic spindle forms. As the cell enters mitosis, the nuclear envelope invaginates beside the SPB, forming a pocket of cytoplasm that accumulates dark amorphous material. The nuclear envelope then opens to form a fenestra, and the duplicated SPB settles into it. Each part of the SPB initiates intranuclear MTs, and then the two structures separate to lie in distinct fenestrae as a bipolar spindle forms. Through metaphase, the SPBs remain in their fenestrae, bound to the polar ends of spindle MTs; at about this time, a small bundle of cytoplasmic MTs forms in association with each SPB. These MTs are situated with one end near to, but not on, the SPBs, and they project into the cytoplasm at an orientation that is oblique to the simple axis. As anaphase proceeds, the nuclear fenestrae close, and the SPBs are extruded back into the cytoplasm. These observations define new fields of enquiry about the control of SPB duplication and the dynamics of the nuclear envelope.
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PMCID: PMC276170  PMID: 9285819
19.  Phytochemistry and medicinal properties of Phaleria macrocarpa (Scheff.) Boerl. extracts 
Pharmacognosy Reviews  2013;7(13):73-80.
Phaleria macrocarpa, commonly known as Mahkota dewa is a medicinal plant that is indigenous to Indonesia and Malaysia. Extracts of P. macrocarpa have been used since years in traditional medicine that are evaluated scientifically as well. The extracts are reported for a number of valuable medicinal properties such as anti-cancer, anti-diabetic, anti-hyperlipidemic, anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant and vasorelaxant effect. The constituents isolated from different parts of P. macrocarpa include Phalerin, gallic acid, Icaricide C, magniferin, mahkoside A, dodecanoic acid, palmitic acid, des-acetylflavicordin-A, flavicordin-A, flavicordin-D, flavicordin-A glucoside, ethyl stearate, lignans, alkaloids andsaponins. The present review is an up-to-date summary of occurrence, botanical description, ethnopharmacology, bioactivity and toxicological studies related to P. macrocarpa.
doi:10.4103/0973-7847.112853
PMCID: PMC3731883  PMID: 23922460
Gallic acid; God's crown; magniferin; Mahkota dewa; phalerin; thymelaceae
20.  The Role of the Toxicologic Pathologist in the Post-Genomic Era# 
Journal of Toxicologic Pathology  2013;26(2):105-110.
An era can be defined as a period in time identified by distinctive character, events, or practices. We are now in the genomic era. The pre-genomic era: There was a pre-genomic era. It started many years ago with novel and seminal animal experiments, primarily directed at studying cancer. It is marked by the development of the two-year rodent cancer bioassay and the ultimate realization that alternative approaches and short-term animal models were needed to replace this resource-intensive and time-consuming method for predicting human health risk. Many alternatives approaches and short-term animal models were proposed and tried but, to date, none have completely replaced our dependence upon the two-year rodent bioassay. However, the alternative approaches and models themselves have made tangible contributions to basic research, clinical medicine and to our understanding of cancer and they remain useful tools to address hypothesis-driven research questions. The pre-genomic era was a time when toxicologic pathologists played a major role in drug development, evaluating the cancer bioassay and the associated dose-setting toxicity studies, and exploring the utility of proposed alternative animal models. It was a time when there was shortage of qualified toxicologic pathologists. The genomic era: We are in the genomic era. It is a time when the genetic underpinnings of normal biological and pathologic processes are being discovered and documented. It is a time for sequencing entire genomes and deliberately silencing relevant segments of the mouse genome to see what each segment controls and if that silencing leads to increased susceptibility to disease. What remains to be charted in this genomic era is the complex interaction of genes, gene segments, post-translational modifications of encoded proteins, and environmental factors that affect genomic expression. In this current genomic era, the toxicologic pathologist has had to make room for a growing population of molecular biologists. In this present era newly emerging DVM and MD scientists enter the work arena with a PhD in pathology often based on some aspect of molecular biology or molecular pathology research. In molecular biology, the almost daily technological advances require one’s complete dedication to remain at the cutting edge of the science. Similarly, the practice of toxicologic pathology, like other morphological disciplines, is based largely on experience and requires dedicated daily examination of pathology material to maintain a well-trained eye capable of distilling specific information from stained tissue slides - a dedicated effort that cannot be well done as an intermezzo between other tasks. It is a rare individual that has true expertise in both molecular biology and pathology. In this genomic era, the newly emerging DVM-PhD or MD-PhD pathologist enters a marketplace without many job opportunities in contrast to the pre-genomic era. Many face an identity crisis needing to decide to become a competent pathologist or, alternatively, to become a competent molecular biologist. At the same time, more PhD molecular biologists without training in pathology are members of the research teams working in drug development and toxicology. How best can the toxicologic pathologist interact in the contemporary team approach in drug development, toxicology research and safety testing? Based on their biomedical training, toxicologic pathologists are in an ideal position to link data from the emerging technologies with their knowledge of pathobiology and toxicology. To enable this linkage and obtain the synergy it provides, the bench-level, slide-reading expert pathologist will need to have some basic understanding and appreciation of molecular biology methods and tools. On the other hand, it is not likely that the typical molecular biologist could competently evaluate and diagnose stained tissue slides from a toxicology study or a cancer bioassay. The post-genomic era: The post-genomic era will likely arrive approximately around 2050 at which time entire genomes from multiple species will exist in massive databases, data from thousands of robotic high throughput chemical screenings will exist in other databases, genetic toxicity and chemical structure-activity-relationships will reside in yet other databases. All databases will be linked and relevant information will be extracted and analyzed by appropriate algorithms following input of the latest molecular, submolecular, genetic, experimental, pathology and clinical data. Knowledge gained will permit the genetic components of many diseases to be amenable to therapeutic prevention and/or intervention. Much like computerized algorithms are currently used to forecast weather or to predict political elections, computerized sophisticated algorithms based largely on scientific data mining will categorize new drugs and chemicals relative to their health benefits versus their health risks for defined human populations and subpopulations. However, this form of a virtual toxicity study or cancer bioassay will only identify probabilities of adverse consequences from interaction of particular environmental and/or chemical/drug exposure(s) with specific genomic variables. Proof in many situations will require confirmation in intact in vivo mammalian animal models. The toxicologic pathologist in the post-genomic era will be the best suited scientist to confirm the data mining and its probability predictions for safety or adverse consequences with the actual tissue morphological features in test species that define specific test agent pathobiology and human health risk.
doi:10.1293/tox.26.105
PMCID: PMC3695332  PMID: 23914052
genomic era; history of toxicologic pathology; molecular biology
21.  The maternal autopsy 
Journal of Clinical Pathology  1982;35(9):909-921.
Careful study of reports prepared for the Confidential Enquiries into Maternal Deaths in England and Wales has made it clear that many maternal autopsy reports are not as informative as they might be. This is, in part at least, because no pathologist who does not work in a maternity unit can expect to see more than a handful of such deaths in a working lifetime. This paper describes briefly the particular features to look for at autopsy, stresses the importance of taking adequate material for histology and discusses some of the more significant histological findings, both of conditions which cause death and of those commonly associated with it.
Images
PMCID: PMC497839  PMID: 7119126
22.  Fulvine and the pulmonary circulation 
Thorax  1971;26(3):249-261.
The pyrrolizidine alkaloid, fulvine, is now accepted as a major cause of veno-occlusive disease of the liver in the West Indies, where it is ingested as a decoction of the plant Crotalaria fulva in bush tea. Fulvine is similar in chemical structure to monocrotaline, which is known to cause pulmonary hypertension in rats.
Thirty young female rats were given a single dose of fulvine either by intraperitoneal injection (50 mg/kg body weight) or by stomach tube (80 mg/kg body weight). Eleven of these rats died of acute haemorrhagic centrilobular necrosis of the liver, and two of pneumonia, within 23 days of receiving fulvine. These 13 showed no evidence of hypertensive pulmonary vascular disease. The remaining 17 rats (which survived from 24 to 37 days) developed hypertensive pulmonary vascular disease with right ventricular hypertrophy together with medial thickening of the pulmonary trunk and muscular pulmonary arteries. The pulmonary arterioles showed hypertensive changes and some contained thrombi. In four animals an acute necrotizing arteritis also occurred.
We have shown that fulvine resembles monocrotaline in its ability to produce pulmonary hypertension in rats. We suggest that, in any patient presenting with unexplained pulmonary hypertension, a careful enquiry should be made to elicit the possibility of recent ingestion of drugs or plant extracts that may have caused a rise in the pulmonary arterial pressure.
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PMCID: PMC1019079  PMID: 4253539
23.  A Survey of Small Factories* 
This survey was undertaken by a group of doctors, nurses, and lecturers in the Department of Public Health of the London School of Hygiene and Tropical Medicine as part of the teaching programme for the Diploma in Public Health. Fifty small factories in an area of a metropolitan borough were invited to answer questions concerning their industrial processes, their labour force, their premises, their first-aid provision, and the visits they received from officials of local and central government. Forty-eight of these factories responded and observations were made by teams of three recording independently of each other in 45. A variety of industries was represented in these 48 firms, half of which employed less than 10 workers.
The working environment, in respect of sanitary arrangements, cleanliness and tidiness, lighting on stairs and passage ways, was considered to be unsatisfactory in many firms. Some instances of inadequate safeguards of machines were seen. The accident rate was found to be rather less than the computed national rate for manufacturing industry in 1956.
First-aid equipment and workers were also considered to be deficient in a number of instances. In case of accident and for the treatment of minor ailments most firms made use of a local casualty and out-patient department of a general hospital. This service was considered quite adequate.
Many firms had not been visited by the Factory Inspector or his deputy during the previous year. Rather more had received visits from the local authority health inspectors. Many firms expressed confusion about the duties and functions of their various official visitors.
The conclusions drawn from this limited enquiry were that the working conditions in small factories are often unsatisfactory; that in areas such as the one surveyed it is unrealistic to think in terms of development of an industrial health service similar to those operating in Slough and Harlow; and that the greatest impact on environmental conditions might be made by an improved and simplified system of inspection especially adapted to the needs of the small factory.
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PMCID: PMC1037987  PMID: 14407013
24.  Some aspects of the role of viruses in cancer. 
Postgraduate Medical Journal  1979;55(640):150-158.
The cells of tumours induced by many oncogenic DNA viruses, or cells transformed in vitro, contain virus-specific T and transplantation antigens; these have been described for SV40 virus, polyoma virus and adenoviruses. The investigation of viruses as causes of malignant disease in man has sought to establish whether tumour cells possess these virus-specific proteins; however, to date and with the limitations of present techniques, this enquiry has not demonstrated the above viruses as causal of human cancer. More recent studies with herpesvirus type 2 (HSV-2) have shown this virus to transform animal and human cells in culture, and induce cancer in experimental animals: for these reasons, many researchers have suggested that this agent may be an agent of some forms of cancer, in particular carcinoma of the cervix. The possible association of HSV-2 with human malignant disease is discussed.
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PMCID: PMC2425368  PMID: 223141
25.  Impact Monitoring of the National Scale Up of Zinc Treatment for Childhood Diarrhea in Bangladesh: Repeat Ecologic Surveys 
PLoS Medicine  2009;6(11):e1000175.
Charles Larson and colleagues find that 23 months into a national campaign to scale up zinc treatment for diarrhea in children under age 5 years, only 10% of children with diarrhea in rural areas and 20%–25% in urban/municipal areas were getting the treatment.
Background
Zinc treatment of childhood diarrhea has the potential to save 400,000 under-five lives per year in lesser developed countries. In 2004 the World Health Organization (WHO)/UNICEF revised their clinical management of childhood diarrhea guidelines to include zinc. The aim of this study was to monitor the impact of the first national campaign to scale up zinc treatment of childhood diarrhea in Bangladesh.
Methods/Findings
Between September 2006 to October 2008 seven repeated ecologic surveys were carried out in four representative population strata: mega-city urban slum and urban nonslum, municipal, and rural. Households of approximately 3,200 children with an active or recent case of diarrhea were enrolled in each survey round. Caretaker awareness of zinc as a treatment for childhood diarrhea by 10 mo following the mass media launch was attained in 90%, 74%, 66%, and 50% of urban nonslum, municipal, urban slum, and rural populations, respectively. By 23 mo into the campaign, approximately 25% of urban nonslum, 20% of municipal and urban slum, and 10% of rural under-five children were receiving zinc for the treatment of diarrhea. The scale-up campaign had no adverse effect on the use of oral rehydration salt (ORS).
Conclusions
Long-term monitoring of scale-up programs identifies important gaps in coverage and provides the information necessary to document that intended outcomes are being attained and unintended consequences avoided. The scale-up of zinc treatment of childhood diarrhea rapidly attained widespread awareness, but actual use has lagged behind. Disparities in zinc coverage favoring higher income, urban households were identified, but these were gradually diminished over the two years of follow-up monitoring. The scale up campaign has not had any adverse effect on the use of ORS.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Diarrheal disease is a significant global health problem with approximately 4 billion cases and 2.5 million deaths annually. The overwhelming majority of cases are in developing countries where there is a particularly high death rate among children under five years of age. Diarrhea is caused by bacterial, parasitic, or viral pathogens, which often spread in contaminated water. Poor hygiene and sanitation, malnutrition, and lack of medical care all contribute to the burden of this disease. Replacing lost fluids and salts is a cheap and effective method to rehydrate people following dehydration caused by diarrhea. Clinical trials show that zinc, as part of a treatment for childhood diarrhea, not only helps to reduce the severity and duration of diarrhea but also reduces the likelihood of a repeat episode in the future. Zinc is now included in the guidelines by the World Health Organization (WHO)/UNICEF for treatment of childhood diarrhea.
Why Was This Study Done?
Zinc treatment together with traditional oral rehydration salts therapy following episodes of diarrhea could potentially benefit millions of children in areas where diarrheal disease is prevalent. The “Scaling Up of Zinc for Young Children” (SUZY) project was established in 2003 to provide zinc treatment for diarrhea in all children under five years of age in Bangladesh. The project was supported by a partnership of public, private, nongovernmental organization, and multinational sector agencies during its scale up to a national campaign across Bangladesh. The partners helped to develop the scale-up campaign, produce and distribute zinc tablets, train health professionals to provide zinc treatment, and create media campaigns (such as advertisements in TV, radio, and newspapers) to raise awareness and promote the use of zinc for diarrhea. The researchers wanted to monitor how effective and successful the national campaign was at promoting zinc treatment for childhood diarrhea. Also, they wanted to highlight any potential problems during the implementation of health care initiatives in areas with deprived health systems.
What Did the Researchers Do and Find?
The researchers set up survey sites to monitor results from the first two years of the SUZY campaign. Four areas, each representing different segments of the population across Bangladesh were surveyed; urban slums, urban nonslums, municipal (small city), and rural. There are approximately 1.5 million children under the age of five across these sites. Households in each survey site were selected at random, and seven surveys were conducted at each site between September 2006 and October 2008—about 3,200 children with diarrhea for each survey. Over 90% of parents used private sector providers of drug treatment so the campaign focused on distribution of zinc tablets in the private sector. They were also available free of charge in the public health sector. TV and radio campaigns for zinc treatment rapidly raised awareness across Bangladesh. Awareness was less than 10% in all communities prelaunch and peaked 10 months later at 90%, 74%, 66%, and 50% in urban nonslum, municipal, urban slum, and rural sites, respectively. However, after 23 months only 25% of urban nonslum, 20% of municipal and urban slum, and 10% of rural children under five years of age were actually using zinc for childhood diarrhea. Use of zinc was shown to be safe, with few side-effects, and did not affect the use of traditional treatments for diarrhea. Researchers also found that many children were not given the correct ten-day course of treatment; 50% of parents were sold seven or fewer zinc tablets.
What Do These Findings Mean?
These findings show that the first national campaign promoting zinc treatment for childhood diarrhea in Bangladesh has had some success. Addition of zinc tablets for diarrhea treatment did not interfere with existing therapies. Mass media campaigns, using TV and radio, were useful for promoting health care initiatives nationwide alongside the education of health care providers and care-givers. The study also identified areas where more work is needed. Surveys in more remote, hard to reach sites in Bangladesh would provide better representation of the country as a whole. High awareness of zinc did not translate into high use. Repeated surveying in the same subdistricts may have overestimated actual awareness levels. Furthermore, mass media messages must link with messages from health care providers to help to reinforce and promote understanding of the use of zinc. A change in focus of media messages from awareness to promoting household decision-making may aid the adoption of zinc treatment for childhood diarrhea and improve adherence.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000175
The International Centre for Diarrhoeal Disease Research, Bangladesh Web site has information about the study
The World Health Organisation provides information on diarrhea
The study was sponsored by the Bill & Melinda Gates Foundation
doi:10.1371/journal.pmed.1000175
PMCID: PMC2765636  PMID: 19888335

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