Problem drinking has been identified as a major risk factor for physical intimate partner violence (PIPV) in many studies. However, few studies have been carried on the subject in developing countries and even fewer have a nationwide perspective. This paper assesses the patterns and levels of PIPV against women and its association with problem drinking of their sexual partners in a nationwide survey in Uganda.The data came from the women’s dataset in the Uganda Demographic and Health Survey of 2006. Problem drinking among sexual partners was defined by women’s reports that their partner got drunk sometimes or often and served as the main independent variable while experience of PIPV by the women was the main dependent variable. In another aspect problem drinking was treated an ordinal variable with levels ranging from not drinking to getting drunk often. A woman was classified as experiencing PIPV if her partner pushed or shook her; threw something at her; slapped her; pushed her with a fist or a harmful object; kicked or dragged her, tried to strangle or burn her; threatened/attacked her with a knife/gun or other weapon. General chi-square and chi-square for trend analyses were used to assess the significance of the relationship between PIPV and problem drinking. Multivariate analysis was applied to establish the significance of the relationship of the two after controlling for key independent factors.trend < 0.001). Similar relationship was found between wealth status and experiencing PIPV.Results show that 48% of the women had experienced PIPV while 49.5% reported that their partners got drunk at least sometimes. The prevalence of both PIPV and problem drinking significantly varied by age group, education level, wealth status, and region and to a less extent by occupation, type of residence, education level and occupation of the partner. Women whose partners got drunk often were 6 times more likely to report PIPV (95% CI: 4.6-8.3) compared to those whose partners never drank alcohol. The higher the education level of the women the less the likelihood of experiencing PIPV (pProblem drinking among male partners is a strong determinant of PIPV among women in Uganda. PIPV prevention measures should address reduction of problem drinking among men. Longerterm prevention measures should address empowerment of women including ensuring higher education, employment and increased income. Intimate partner violence (IPV) is a widespread form of gender-based violence. IPV is commonly defined as violence by one adult perpetrated on another, both parties being involved in an intimate relationship as a spouse or sexual partner . IPV incIPV has a direct impact on women’s health ,8 and chCompared to other forms of IPV it is easier to measure physical intimate partner violence (PIPV) and compare this between countries since more work has been done with this construct compared to other forms of IPV. Another challenge with using alternative definitions of IPV, such as those that include sexual violence, is that these have more varying definitions and hence systematic comparative data across countries are less available . TherefoAlcohol consumption reduces self control and affects cognitive and physical functioning which reduces the ability of an individual to negotiate non-violent conflict resolution . AlcoholDetailed analysis in several studies has found that it is problem drinking that contributes most to PIPV rather than just drinking alcohol ,19. A stApart from problem drinking, many other factors are recognized as contributing to PIPV. Some of these factors include poverty, lack of women’s empowerment , urban rLevels of PIPV vary widely across countries but they tend to be higher in developed than developing countries. A multi-country study commissioned by WHO and conducted from 2000 to 2003 found that the lifetime prevalence of PIPV ranged from 13% in Japan to 61% in Peru. In the same study Tanzania, which neighbours Uganda, had a PIPV prevalence of 47% . In a suth in the world [Uganda has high per capita alcohol consumption and high prevalence of PIPV. In 2004 Uganda had the highest per capita alcohol consumption in the world with an average of 19.4 l per capita . Despitehe world . A studyhe world . In the he world . Regardihe world .According to the 2006 Uganda Demographic and Health Survey (UDHS), 48% of ever-married women experienced physical violence by their partners, and this proportion was much higher than that of physical violence against men (20%) . Given tMuch is known about factors associated with PIPV and alcohol consumption but relatively less is known about the association between problem drinking and PIPV in developing countries, especially in Africa. Furthermore, most of the few studies carried out in Africa have not had a nationwide perspective. This paper presents the prevalence of PIPV committed against women and the prevalence of problem drinking among their partners, as well as the association between PIPV and problem drinking.The data analyzed for this paper came from the women’s data set of the Uganda Demographic and Health Survey (UDHS) of 2006, conducted by Macro International, Inc. and the Uganda Bureau of Statistics (UBOS). The data set is openly available. The sample for the survey was drawn using a two-stage cluster sampling technique where the Primary Sampling Unit (PSU) was an Enumeration Area (EA) demarcated from the 2002 national census. In the first stage 368 PSUs were randomly selected using Probability Proportional to Size (PPS) from EAs listed by district and rural/urban residence. The same list of EAs had been used in the 2005 national household survey . In the The UDHS survey reached 8,531 women aged 15–49 but only 2,087 (24.5%) were randomly selected for the interview on domestic violence while 1,748 (20.5%) were asked questions specifically on violence against them by their male sexual partners . Only 1,743 of the 1748 provided answers to questions on both PIPV and alcohol consumption. Computation of the prevalence of PIPV and significance testing of its variation by different background characteristics were based on weighted data. The overall eligible women response rate of the survey was 95% .PIPV referred to events when a male partner to the respondent did any of the following in previous 12 months to the respondent: pushed, shook or threw something at her, slapped, punched with fist or with something harmful that could hurt her, kicked or dragged or beat her, tried or actually choked or burnt her on purpose, threatened or attacked her with a knife/gun or other weapon . While iThe UDHS survey probed alcohol consumption of each woman’s partner including whether her partner drank alcohol and, if he did, how often he got drunk. Answers to the two questions were used to create a new drinking variable with the following categories: i) does not drink ii) drinks but never gets drunk iii) gets drunk sometimes iv) gets drunk very often. For defining the prevalence of problem drinking the variable was dichotomized: ever got drunk versus never drank or drank but did not get drank.The dependent variable was experience of PIPV by the respondent while the key independent variable was problem drinking of the male partner. Independent variables investigated for moderating effects of the relationship between PIPV and problem drinking were age group of the women, their marital status, participation in decision making at home, religion, region, type of residence , education level, occupation, wealth quintile, age difference with partner, education level of the partner and occupation of the partner. The regions are Central, Kampala city, Eastern, Northern and Western Uganda. The wealth quintiles were developed for all women using household assets, services, and amenities . To asseData analysis was carried out using STATA V10 and it started with general description of the sample in terms of socio-demographic characteristics. The prevalence of problem drinking was computed using the general sampling weights while that of PIPV was computed using special partner violence weights. Both weights were provided in the data set. The chi-square test of significance was applied to assess the significance of the variation in the proportions.The next stage of analysis involved multivariate logistic regression of the relationship between PIPV and problem drinking. Here the four level problem drinking variable was used in order to assess the effects of each level of problem drinking on PIPV. Both unadjusted and adjusted odds ratios for being a victim of PIPV are presented together with their 95% confidence intervals. Multivariate backward elimination criteria was applied with inclusion criteria of p < =0.1 for variables from the bivariate analysis. The p-value of 0.1 is midway between the more inclusive criteria of 0.2 and less inclusive criteria of 0.05. Variables were excluded from the models depending on the contribution to goodness of fit of the models  and WaldMost of the women were of young or middle age with 69% 1,198) under 35 years. Twenty three percent (408) had not attained any formal education while only 14%(250) had attained secondary education  of the women reported that their partners were uneducated while 29% (457) said their partners attained at least secondary education. Fifty two percent of the women (829) said their partners were engaged in agriculture or were self employed.Regarding age difference with their partners, 36% of the women reported that their partners were 1–4 years older than them, 33% being 5–9 years older and 23% 10 or more years older.trend = 0.02) and, the higher the education level of the women the less the likelihood of having experienced PIPV (ptrend < 0.001). Similarly, the higher the wealth status of the women the less the likelihood of having experienced PIPV (ptrend < 0.001). The prevalence of PIPV among the women did not significantly vary by participation in decision making and age difference with their partners.The overall prevalence of PIPV was 48%. PIPV varied significantly by age group of the women (p = 0.003), education level, p < 0.001), residence (p < 0.001), marital status (p = 0.01), region (p < 0.001), religion (p < 0.001), occupation (p < 0.001), wealth status (p < 0.001), education level of the partner (p < 0.001) and occupation of the partner (p = 0.007) . The higher the education level of a woman the lower the likelihood of having a partner who got drunk (ptrend < 0.001). Similarly, the wealthier the household of a woman the lower the likelihood of having a partner who got drunk. The problem drinking of the partners was most commonly reported by women from rural areas, from the western region, Catholics, those employed in manual labour, the poorest and those whose partners were in agriculture and self employed. The proportion of women whose partners got drunk did not significantly vary by participation in decision making and age difference with their partners.Fifty six percent of the women reported that their partners drank alcohol. The proportion of women who reported that their partners got drunk was 49.5% and this represented 88% of those whose partners drank alcohol (56.0%). The levels and demographic patterns of PIPV were similar to those of problem drinking. Like PIPV the level of problem drinking significantly varied by age group (p < 0.001), educational level (p = 0.001), residence (p < 0.001), region (p < 0.001), religion (p < 0.001), occupation (p = 0.001), wealth status (p < 0.001), education level and occupation of partner (p < 0.001). The proportion of women who reported that their partners got drunk was lowest (42%) among those aged 15–24 but rose to 52% in next age group. The older the women the higher the likelihood of having a partner that got drunk (ptrend < 0.001).Table The relationship between problem drinking of the women’s partner and likelihood of experiencing PIPV remained strong after controlling for age group, region and wealth status. In terms of contribution to the overall significance of the model problem drinking contributed most (p < 0.001) compared to age group (p = 0.15), wealth (p = 0.016) and region (p = 0.002). Education also contributed highly (p < 0.001) but had a lower chi-square value (23) compared with problem drinking (166) for the same degrees of freedom (3). Therefore, problem drinking was the strongest correlate of PIPV. The adjusted odds ratios for levels of problem drinking remained virtually the same. The model fitted well with Pearson’s chi-square test p-value of 0.72 which was greater than 0.05 expected of well fitting models . EducatiThe results showed that the population prevalence rates of PIPV against women in Uganda and problem drinking of their partners are quite high . The level of PIPV against women is higher than the levels reported for the USA , Canada (7%) and Japan (13%) ,38. HoweThe findings about problem drinking, and particularly getting drunk, being the strongest predictor of PIPV among those factors investigated  are similar to those in previous studies in the UK and the USA ,21. The The findings indicate that PIPV may not have much relationship with the male partner’s simple consumption of alcohol or not but rather his pattern, his pattern of consumption, ever being drank and especially often being so, that is the occurrence and frequency of drunkenness. The proportion of men that drinks alcohol in Uganda is much lower than that of many developed countries but a considerable proportion of drinkers  is reported by their spouses to be occasionally drunk. For example 88% of men take alcohol in the UK  as opposThe high proportion of individuals who drink alcohol in UK, with relatively lower rates of PIPV is probably due to a lower proportion of men who get drunk among those who consume alcohol. Our findings show similar levels of PIPV among men who do not drink and those who drink but do not get drunk. This study has further shown that drinking that leads to obvious intoxication that a spouse might detect and report, can be dangerous. This indicates that governments can mitigate the PIPV problem by focusing more on reduction of problem drinking rather than completely stopping people from drinking, which would be a tougher task. This is also in line with WHO advice on reducing PIPV through moderating alcohol consumption . Most ofMost of the independent factors examined for a relationship with PIPV were found significant but none moderated the relationship between PIPV and problem drinking of the sexual partners of the women. The strength of the relation between problem drinking and PIPV did not even change by different levels of significant correlates of PIPV like age group, region, wealth status and education. This underlines the need for further studies to identify factors that might substantially modify the relationship between alcohol consumption and PIPV.Findings of higher risk of PIPV among those with less education attainment, low wealth status are consistent with several studies -26. Our While most of the findings in this study are consistent with some of the previous research done a few are inconsistent. PIPV was more common in rural areas and among older people but in research in other countries it was found more common in urban areas  and amonOur study findings are subject to several limitations. The information on male partners’ drinking habits and PIPV was provided by the women, introducing the possibility of self-report data errors and misclassification biases. Classifying the frequency of drunkenness as often or sometimes was also subjective lacking specific frequency-in-time information. Nevertheless, we believe it to be a noteworthy strength of the study that women, who bear the largest burden of PIPV, and also experience the externalities associated with partners’ problem drinking, which they can observe, are the source of the reports.Secondly, the period in which PIPV and problem drinking occurred may have involved different time periods depending on length of the relationship of the respondent and her partner. This brings with it potential for recall bias, which could in future be better addressed by adding queries of the timing between PIPV and problem drinking. Being based on a cross-sectional self-report survey, it is inherently difficult to tell whether PIPV started after problem drinking or it was the reverse, or that both occurred in approximately the same period. However, this study highlights associations between problem drinking and IPV as well as estimating the influences of women’s education, their empowerment, their partners’ education and their socio-economic status in mitigating this harm. These findings have importance for informing interventions for IPV in Uganda and elsewhere, and can help to generate hypotheses regarding PIPV and alcohol consumption to motivate and sharpen the focus of further research efforts.The prevalence of reported PIPV among women and problem drinking among their partners are relatively high in Uganda. There is a very strong association between experience of PIPV among women and problem drinking of their partners. The more often men get drunk the more they are likely to inflict PIPV against their spouses.Besides problem drinking lower education attainment, low wealth status, higher age group and region are correlated with PIPV. Although results are cross-sectional and causality cannot be established, results are consistent with the notion that increasing education levels of women and their partners would have the potential to reduce exposure to PIPV. Similarly, increasing wealth or socio-economic status of women in general might reduce the risk of PIPV.Among the strengths of this study are that the survey provided nationwide coverage and involved women respondents who are most affected by PIPV. The sample size was large enough to allow reliable prevalence estimation, and significance testing of demographic differences in prevalence of PIPV and drunkenness. Finally, analysis of multivariate models that predict PIPV and include problem drinking while controlling for other important factors brings out the importance of victimization, drunkenness, or problem drinking in Uganda, an important African country because of its high levels of both problem drinking and physical IPV.More effort is required to reduce PIPV and problem drinking in Uganda. Freedom from violence is a basic human right, and policies to reduce physical intimate partner violence (PIPV) need to incorporate strategies to regulate heavy alcohol consumption among men as well as improve education and empowerment of women. Campaigns against PIPV should focus more on the older people, the less educated and the poor, as part of addressing regional economic and social development. Additional information for targeting PIPV prevention programs are suggested because of elevated levels seen among rural residents, Christians, and those employed in manual labour and peasant farming. Examples of related campaigns that have made a significant difference include the “raising voices” programme in Uganda which used discussions on use of power to discourage wife and child beating and the “we can” campaign of Oxfam in Asia which significantly increased awareness of gender equity and rejection of violence .Future Demographic and Health surveys or other nationwide surveys should add additional questions and specific measures of heavy drinking, for example maximum amount consumed on any day and number of drinks to feel drunk, as well as of circumstances surrounding the intimate partner violence, so as to enable more detailed analysis of alcohol consumption patterns and their relationship with PIPV. More research should be carried out to identify evidence-informed interventions to mitigate problem drinking and PIPV.Now that many studies have established an association between alcohol use and PIPV there is a need for meta-analysis and Cochrane reviews to provide more authoritative evidence on the relationship between the two.None identified. The author(s) declare that they have no competing interests.All authors read and approved the final manuscript. NMT initiated the topic, analyzed the data and wrote the first draft of the paper. GKB and TKG made critical input and comments on the draft manuscript. RKW contributed to the interpretation and writing of the paper.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/12/399/prepub


Shigella causes an estimated 160 million infections and >1 million deaths annually. However, limited incidence data are available from African urban slums. We investigated the epidemiology of shigellosis and drug susceptibility patterns within a densely populated urban settlement in Nairobi, Kenya through population-based surveillance.Worldwide, Surveillance participants were interviewed in their homes every 2 weeks by community interviewers. Participants also had free access to a designated study clinic in the surveillance area where stool specimens were collected from patients with diarrhea (≥3 loose stools within 24 hours) or dysentery (≥1 stool with visible blood during previous 24 hours). We adjusted crude incidence rates for participants meeting stool collection criteria at household visits who reported visiting another clinic.Shigella species were isolated from 224 (23%) of 976 stool specimens. The overall adjusted incidence rate was 408/100,000 person years of observation (PYO) with highest rates among adults 34–49 years old . Isolates were: Shigella flexneri (64%), S. dysenteriae (11%), S. sonnei (9%), and S. boydii (5%). Over 90% of all Shigella isolates were resistant to trimethoprim-sulfamethoxazole and sulfisoxazole. Additional resistance included nalidixic acid (3%), ciprofloxacin (1%) and ceftriaxone (1%).Shigella vaccines.More than 1 of every 200 persons experience shigellosis each year in this Kenyan urban slum, yielding rates similar to those in some Asian countries. Provision of safe drinking water, improved sanitation, and hygiene in urban slums are needed to reduce disease burden, in addition to development of effective  Shigella is responsible for >160 million infections in developing countries with an estimated 1.1 million deaths Shigella. Persons with diarrhea are primarily responsible for transmission Shigella highly infectious Musca domestica, may serve as vectors for transmission Although rates have decreased in middle-income and wealthy nations, shigellosis remains a major public health problem in impoverished settings because of sub-optimal sanitation and hygiene and contaminated water supplies Shigellae is increasing worldwide Shigella have reduced antimicrobial therapeutic options and increased cost of therapy Symptoms of shigellosis typically include diarrhea and/or bloody stools with abdominal cramps and tenesmus Previous estimates of the burden of shigellosis in developing countries may have underestimated its magnitude. Studies present varying incidence and prevalence rates, because of divergent methods and intrinsic disparities among the populations studied Since 2005, the Centers for Disease Control and Prevention (CDC) and the Kenya Medical Research Institute (KEMRI) have maintained population-based infectious disease surveillance (PBIDS) in a geographically defined area within an urban informal settlement in Nairobi, Kenya The urban PBIDS system is based in Kibera, a large informal settlement (urban slum) in Nairobi, Kenya. Kibera lacks adequate sanitation facilities; human and animal wastes drain into open sewage runoff. Drinking water is often obtained from unregulated vendors using illegal connections to a municipal piped water system, a situation that facilitates contamination of water supplies. Food is traded at unregulated outdoor markets that often lack basic hygiene standards.2 area . The surveillance area was divided into 10 pre-defined geographic zones roughly based on pre-existing sub-village designations. Trained community interviewers visited enrolled participants fortnightly from March 1, 2007 through Jan 31, 2010 and, thereafter every week collecting data on illnesses and deaths since the previous visit. The frequency of household visits was increased to shorten the recall period during the pandemic of influenza A (H1N1). Shortened recall period was found to improve accuracy of data collected during household visits The PBIDS procedures have been described previously From January 1, 2007 through December 31, 2010, we collected stool samples from consenting patients who met the following criteria:Uncomplicated diarrhea (defined as ≥3 loose stool within a 24-hour period) without signs or symptoms of dehydration or dysentery. (To minimize burden on the laboratory we sampled a maximum of 6 stool specimens from patients with uncomplicated diarrhea per day: 3 from patients <5 years old and 3 from patients ≥5 years old);Complicated diarrhea based on the presence of symptoms or signs of dehydration, defined as: drinking eagerly or unable to drink or breastfeed, vomiting everything, slow skin pinch return (≥2 seconds), irritability, sunken eyes, lethargy or unconsciousness ;Dysentery, defined as reported or visible blood in ≥1 stool within 24 hours of clinic visit .Shigella isolated from stool.A case of shigellosis was defined as a patient meeting any of the above criteria who had We provided each consenting participant meeting the stool collection criteria with a labelled stool container and instructions on how to sample their stool; placing emphasis on including blood or mucus, if present. From May 2008, patients visiting the clinic who were unable to provide a stool sample while at the clinic were sent home with a labelled container to collect a stool specimen. A sample collector was then sent to the patient's home to collect the specimen within 4 hours after the clinic visit. Swabs of whole stool specimens were placed in Cary-Blair transport medium, refrigerated at 4–8 °C then transported to the KEMRI-CDC enteric microbiology laboratory in Kisumu from Jan 2007 to May 2009; thereafter, stool specimens were processed in a microbiology laboratory at the study clinic. More than 80% of specimens were processed within 24–28 hours after collection. Specimens were processed using standard microbiological procedures Data were analysed using SAS version 9.1 . We calculated incidence rates as the number of shigellosis cases per 100,000 person-years of observation (PYO), as described previously Shigella cases by the PYO. Our fortnightly and weekly home visit data, provided real time health utilization data for use in assessing what proportion of shigellosis cases were likely missed through clinic-based diarrheal illness testing. Thus, adjusted rate calculations were based on the number of patients who met each of the three stool sample collection criteria (from data collected during home visits) who visited clinics other than the study clinic for their illness; thus, they were ill enough to visit a clinic for their diarrhea or dysentery, but no specimens would have been obtained, as specimens were only collected and processed from patients attending the study clinic. Similar incidence adjustment methods based on health utilization data have been used in other recent studies In calculating crude incidence rates, we divided the number of Shigella numbers for each stool collection criterion and dividing this sum by the total number of person years contributed by participants in the study population . From January, 2007, through April, 2008, few (<5%) patients who met stool collection criteria provided a stool sample for testing, leading to imprecise adjusted incidence rates. Thus, we excluded data from that time period for calculating the crude and adjusted incidence rates. From May 2008, a sample collector was engaged to collect stool samples from patients' homes when patients were unable to provide a sample at the clinic. This resulted in a fivefold increase in the proportion of patients meeting case definitions who provided a stool sample for stool culture, and provided more stable numbers for rate calculations.For characterizing clinical features, drug susceptibility and Logistic regression analysis was used to determine association of clinical features and shigellosis for patients seen at the clinic. Significant unadjusted clinical features (p<0.05) were then entered into a multivariate model to control for confounding. We also examined household data collected from patients confirmed to have shigellosis for a period of one month after the clinic visit when the diagnosis was made to assess the number of hospitalizations and deathsShigella incidence over time using Pearson correlation coefficient. P-values <0.05 were considered significant for all statistical tests.We used incidence rates from this study to project the burden of shigellosis among the estimated 4.3 million people living in informal settlement areas in Kenya The protocol, surveillance questionnaires and consent forms were reviewed and approved by the Ethical Review Committee at the Kenya Medical Research Institute (protocol number 1899) and the Institutional Review Board of CDC- Atlanta (protocol number 4566).Between 1 May, 2008, and 31 Dec, 2010, 77,939 PYO were contributed by persons enrolled into the surveillance system. Adults 18–34 years of age accounted for 35% of the population under surveillance, followed by young adults 10–17 years who accounted for 16%. Males and females contributed equally. The highest proportion of surveillance participants were from Zone 1; 18% followed by zone 10; 16% .Over 80% of enrolled study participants had successful interviews during the biweekly/weekly household visits. By year, this was distributed as follows; 78% in 2007, 74% in 2008, 83% in 2009 and 84% in 2010. During these visits, over 60% of participants who met any of the stool collection criteria and reported visiting any clinic, had visited Tabitha clinic (data not shown). At Tabitha clinic, 7,449 patients met one of the three stool collection criteria . The majShigella bacteria from 1,096 stool specimens collected from patients meeting any of the three stool collection criteria from 1 Jan, 2007, through 31 Dec, 2010: 176 (67%) of Shigella isolates were from patients presenting with dysentery, 83 (32%) from patients with uncomplicated diarrhea and 3 (1%) from patients with complicated diarrhea with dehydration (Shigella bacteria were isolated from 976 stool specimens (data not shown)We isolated 262(24%) ydration . For theThe overall crude incidence rate of shigellosis was 287/100,000 PYO . Crude iShigella isolates were S. flexneri (64%) followed by S. dysenteriae (11%) S. sonnei (9%), and S. boydii (5%). Species could not be determined for 12% of isolates; 6 (22%) of the 27 isolates of S. dysenteriae were type 1  and patients with “uncomplicated” diarrhea were more likely to have evidence of shigellosis than those with a complicated diarrheal illness . Patients with history of vomiting  were less likely to have shigellosis .Over 80% of hoxazole . Three  and three of the sites were in urban slums , where the overall unadjusted incidence of Shigella, further confirming the high burden of shigellosis. Similar estimates in other urban slums in Kenya are lacking. However, two studies performed in rural western Kenya also found high Shigella isolation rates of 15% and 16% of stool samples collected from patients presenting with diarrhea or dysentery In our study, over 20% of all stool samples yielded Shigella isolated from stool than patients presenting with non-dysenteric diarrhea As expected, patients presenting with dysentery were more likely to have Shigella; however, it is conceivable that they had a greater risk of being infected by young children.Females in the 35–49 year age group had a higher incidence of shigellosis, than males in the same age group. It is not clear why women in this age group were at increased risk of being infected with Shigella may occur annually in Kenyan urban slums.Our adjusted rates suggest that over 0.4% of people living in urban slum settings are stricken with shigellosis annually. Like other developing countries, Kenya is experiencing rapid urbanization (>3%/year) and migrants from rural to urban areas tend to settle in slums S. flexneri was the most common species of Shigella identified in our study population As in other developing countries Shigella was isolated throughout the year. This may be explained by the lack of adequate sanitary facilities and raw sewage flowing all year round in open drainage channels to which children are exposed potentially providing constant exposure to Shigella.Shigella isolates were resistant to commonly available and affordable antibiotics, consistent with findings of previous studies from Africa Salmonella strains Many of the ShigellaShigella during shipping and storage.While this study was unique in terms of its active surveillance for shigellosis and for providing reliable basis for rate adjustments, limitations may have led to underestimates or overestimates of the burden of disease. Because of transport requirements to the Kisumu laboratory, some stool specimens were processed >24 hours after collection. Cary-Blair solution preserves viability of In calculating, adjusted incidence rates, we assumed that persons with diarrhea who reported visiting any clinic had similar shigellosis incidence rates as those seen in the study field clinic. This assumption could be erroneous if there was a systematic bias in which persons with shigellosis tended to go to the designated study clinic at different rates than persons with other causes of diarrhea or dysentery. We believe that use of non-study field clinics occurred primarily because the study clinic was open only Monday-through-Friday during daylight hours; thus, we do not think that there would be intrinsic biases in the way we adjusted the incidence rates. We did not adjust the incidence rates based on the proportion of patients who met the case definition and did not provide a stool specimen. This is because a relatively small proportion of patients meeting our diarrhea case definitions provided stool specimen, which would have made further adjustments imprecise, potentially exaggerating the adjusted incidence rates. On the other hand, opting not to make this adjustment likely led to underestimation of incidence rates. In addition, patients with dysentery were more likely to provide a stool sample for culture and sensitivity studies compared to patients presenting with non-bloody diarrhea. This led to a higher adjustment factor among patients with diarrhea (without dysentery), which may over estimate the burden of shigellosis in this category of patients.Drinking water, sanitation, and hygiene improvements within the rapidly multiplying and expanding informal settlements in Kenya, and elsewhere in Africa, are needed to reduce the risk of shigellosis and other enteric infections. Health education, including a focus on hand washing with soap, provision of safe drinking water and proper waste disposal are feasible strategies for containing the burden of shigellosis


The heat content anomaly for the upper 700 m, showed a sharp increase from coast (0.46 Wm−2) to ocean (1.59 Wm−2). The difference between coastal and ocean values was related to the presence of coastal upwelling, which partially inhibits the warming from surface of near shore water.Temperature is observed to have different trends at coastal and ocean locations along the western Iberian Peninsula from 1975 to 2006, which corresponds to the last warming period in the area under study. The analysis was carried out by means of the Simple Ocean Data Assimilation (SODA). Reanalysis data are available at monthly scale with a horizontal resolution of 0.5°×0.5° and a vertical resolution of 40 levels, which allows obtaining information beneath the sea surface. Only the first 21 vertical levels (from 5.0 m to 729.35 m) were considered here, since the most important changes in heat content observed for the world ocean during the last decades, correspond to the upper 700 m. Warming was observed to be considerably higher at ocean locations than at coastal ones. Ocean warming ranged from values on the order of 0.3°C dec The warming experienced by the world’s oceans over the last century was not uniform either in time or in space The variables most widely used to analyze the ocean warming have been the sea surface temperature (SST) and the ocean heat content. Both variables are complementary providing information about surface temperature trends and heat stored in the ocean between surface and a depth which typically ranges from 700 to 3000 m. In general, most of authors consider the upper 700 m since, according to To examine the role played by the ocean in climate change it is necessary to have an appropriate database in order to analyze the variables that can be used to describe the ocean variability. During the last decades, the most commonly used ocean database has been the World Ocean Database The aim of this study is to describe the differences in the variability of temperature and heat content between coastal and ocean locations along the western Iberian Peninsula from 1975 to 2006. This analysis will be carried out by means of data obtained from SODA reanalysis. As far as we know, only SST patterns had been considered in the study area. In the present study, information about the vertical structure of temperature changes will also be provided.Data and Methods section. Costal water is observed to be considerably colder than ocean water at the same latitude, showing the imprint of coastal upwelling.The area located in front of the Western Iberian Peninsula (from 37.25 to 43.25°N and from 9.75 to 14.75°W) has been considered. This region is characterized by a shoreline perpendicular to the equator, being coastal upwelling the main driving mechanism (see −1), is considerably lower than in the ocean (0.25–0.35°C dec−1). Temperature trends were also calculated for the thermocline base , is found at ocean locations covering the upper 300 m. On the contrary, the warming hardly attains 0.2°C dec−1 near shore and only affects the upper 20 m, being practically negligible (<0.1°C dec−1) below 50 m. These common features can also be observed at the rest of latitudes from 38.25 to 43.25°N (not shown).Vertical profiles of temperature trends were used to analyze the water column . Profile−1 are observed near surface at the ocean decreasing with depth till reaching values below 0.1°C dec−1 at 500 m. The coastal warming is much smaller, reaching values close to 0.2°C dec−1 near surface and decreasing rapidly at values below 0.1°C dec−1 for depths on the order of 50 m.The vertical profile of coastal temperature trends , to ocean, 3.7×1018 J (1.59 Wm−2). Error bars were calculated using the standard deviation of the monthly data, σ(Q), divided by the square root of the number of data.Once the difference between coastal and ocean warming has been analyzed, we will quantify the changes observed in heat anomaly (Q), which was calculated from temperature anomaly following Eq. 1 in 975–2006 . Q shows18J dec−1) at ocean locations and a smoother one (∼0.6×1018J dec−1) at coastal locations.The time evolution of heat anomaly  is also −1) than at the ocean (0.25–0.35°C dec−1). These values are similar to SST trends observed for the same area near shore (∼0.15°C dec−1) over the period 1985–2005 −1 near shore and 0.30°C dec−1 at open sea locations) were found over the period 1974–2008 −1) over the period 1974–2007 for the NW corner of the Iberian Peninsula The difference in SST warming rates between near coast and at ocean locations had been previously described for the Western Iberian Peninsula −1) near surface (upper 20 m), which decreases rapidly and becomes negligible below 50 m. On the contrary, the ocean vertical profile shows a stronger surface warming (0.2–0.4°C dec−1), which penetrates down to 300 m. That ocean vertical profile of temperature trend is similar to the warming decrease with depth described for the Bay of Biscay along the upper 400 m −1) at subsurface layer, which is similar to the one observed in the present study (∼0.32°C dec−1) for ocean locations. In addition, their trend does not decrease abruptly during the first tens of meters but it remains positive till approximately 500 m. The same was observed in our study, where trends on the order of 0.05°C dec−1 are observed at 600 m. Note that study described in The meridional average of trends was calculated for coastal and ocean locations considering all latitudes ranging from 38.25 to 43.25°N . The coa−1. At ocean locations, the upper layers of the ocean are also affected by the warming observed for air temperature. There, heat is mainly transported down from surface to lower layers by thermal diffusion. Near shore, coastal upwelling is the most important forcing mechanism, in such a way that cold water is pumped intermittently from below to near surface layers. Thus, diffusion is offset by advection, which mixes deeper colder water with warmer surface water. Thus, diffusive atmospheric heating is constrained to near surface layers, resulting in a weaker coastal warming. This difference in coastal and ocean warming rates is not necessarily correlated with changes in upwelling intensity. In fact, the mechanism proposed in It should be noted that the area has suffered a noticeable warming from 1975 on. Actually, according to −2) to ocean (1.59 Wm−2). The increment for the ocean is considerably higher than that obtained for the world ocean (0.20 Wm−2) and for the Atlantic Ocean (0.52 Wm−2) −2 for the world ocean over the period 1969–2008 considering the upper 700 m −2 was detected for the world ocean over the period 1993–2008 considering the upper 700 m −2 can be estimated for the upper North Atlantic (0–700 m) over the period 1968–2003 −2 (0.39 Wm−2) were obtained for the world ocean considering the upper 700 and 2000 m respectively. In the particular case of the Atlantic Ocean, the increase is on the order of 0.54 Wm−2 (0.81 Wm−2) for the upper 700 m (2000 m). Finally, different studies shows that the heat content anomaly calculated using SODA for the band 15°–60° N over the 1961–2001 period The heat content anomaly meridionally averaged from 38.25 to 43.25°N increases from coast (0.46 Wmhttp://www.atmos.umd.edu/~ocean/). For detailed information about the methodology the reader is referred to Sea Temperature data were obtained from the Simple Ocean Data Assimilation (SODA). Reanalysis data covering the period 1958–2008 are available at monthly scale with a horizontal resolution of 0.5°×0.5° and a vertical resolution of 40 levels (ftp://ftp.nodc.noaa.gov/pub/data.nodc/pathfinder/Version5.2/) with an approximate spatial resolution of 4×4 km extending from 1982 to nowadays. Data treatment is described in http://badc.nerc.ac.uk/data/hadisst) Other data bases were considered for comparison purposes. Thus, daily sea surface temperature (SST) data were obtained from daytime measurements carried out by the Advanced Very-High Resolution Radiometer (AVHRR) onboard of NOAA series satellites. Data were retrieved from Pathfinder Version 5.2  was calculated for a transect located at 41.75°N (The comparison among temperature trends (T 41.75°N . Sea temFollowing wc = 3.981×103 J (°C-kg) −1 is the specific heat of seawater at constant pressure at the sea surface, mw = ρwVw is the mass of the seawater block, where wρ = 1.02767×103 kg/m3 is the density and Vw = (0.5×111120)(0.5×111120 cos((2π/180) lat)) ×Δh the volume, being lat the latitude of the water parcel and Δh the water column height from surface to 729.35 m. wc and wρ values were taken from w = dTΔt (°C), where dT is the temperature trend (°C/year) and Δt the period under study (in years).Heat content anomaly was calculated at each grid point over the period 1975–2006 in terms of temperature anomaly, following the expression:Figure S1http://www.atmos.umd.edu/~ocean/), (B) mean SST from Pathfinder (ftp://ftp.nodc.noaa.gov/pub/data.nodc/pathfinder/Version5.2/) and (C) mean SST from HadISST1.1- Global sea- Ice coverage and SST (http://badc.nerc.ac.uk/data/hadisst). Data were averaged over the period 1982–2006. (D) SST trend (°C dec-1) calculated at 41.75°N from 1982 to 2006 using the three data bases mentioned above. SST data were previously re-meshed to a common spatial resolution of 0.5° ×0.5°. Legend in the figure P: Pathfinder; S: SODA; H: HasISST.(A) Mean sea temperature (°C) at surface layer (upper 5 m) from the Simple Ocean Data Assimilation Click here for additional data file.Figure S2Mixed layer depth (MLD) at two transects located at 41.75°N (black line) and 39.75°N (gray line). The MLD was calculated following the temperature criterion SST -ST(z) = 0.2°C, where ST(z) is the water temperature at depth (z) (TIF)Click here for additional data file.


Oral Squamous Cell Carcinoma (OSCC) is biologically characterized by the accumulation of multiple genetic and molecular alterations that end up clinically characterized as a malignant neoplasm through a phenomenon known as multistep. The members of the Cip/Kip family, specifically p21Waf1/CIP1, are responsible for cell cycle control, blocking the transition from phase G1 to phase S. We made a search of articles of peer-reviewed Journals in PubMed/ Medline, crossing the keywords. The goal of this paper is to determine the relationship between p21Waf1/CIP1 expression and several clinical and pathological aspects of OSCC, their relationship with p53 and HPV, as well as genetic alterations in their expression pattern, their use as a prognosis market in the evolution of precancerous lesions and their roles in anticancer treatments. The results of p21WAF1/CIP1 expression in OSCC showed mixed results in terms of positivity/negativity throughout different studies. It seems that, although p21Waf1/CIP1 expression is controlled in a p53-dependent manner, coexpression of both in OSCC is not intrinsically related. Although the presence of HPV viral oncoproteins increases p21Waf1/CIP1 levels, the small number of studies, have forced us to disregard the hypothesis that HPV infected lesions that present better prognosis are due to a p21Waf1/CIP1–dependent control. The role of p21WAF1/CIP1 as cell-cycle regulator has been well described; however, its relationship to OSCC, the clinical and pathological variables of tumors, HPV and different treatments are not entirely clear. Thus, it would be very interesting to pursue further study of this protein, which may have a significant value for the diagnosis, prognosis and therapy of this type of tumors. Key words:p21Waf1/CIP1, Cip/Kip type cell-cycle regulator, Oral squamous cell carcinoma (OSCC), p53, genetic alterations. Oral Squamous Cell Carcinoma (OSCC) is biologically characterized by the accumulation of multiple genetic and molecular alterations that end up clinically characterized as a malignant neoplasm through a phenomenon known as multistep. The accumulation of damaged genetic material leads oral keratinocytes in an uncontrolled division of mutant cells .Control of the cellular cycle is regulated by cyclins and cyclin-dependent kinases (CDK). The activity of these enzymes is restricted by the inhibiting action of two great (CDKI) inhibitor groups: the INK4 family, comprised by inhibitors p16, p15, p18 and p19; and the Cip/Kip family, comprised by p27, p57 and p21  p21Waf1/CIP1 was initially identified as a 21 kDa protein that inhibited activation of cyclin/CDK (Cip1) complexe, later it was identified as an overexpressed gene in senescent cells, located at 6p21.1 (sdi1); furthermore p21 gene product, is transcriptionally activated by p53 in case of damage to DNA (WAF1). p21 is regulated by two different pathways, through a p53-dependent pathway (DNA damage leads to activation of p53 and upregulation of p21 causing cell cycle blockage in G1 phase with possible DNA repair or induction of apoptosis); and a p53-independent way, through which cell growth factors  .We made a search of articles of peer-reviewed Journals in PubMed/ Medline, crossing the keywords. The goal of this paper is to determine the relationship between p21Waf1/CIP1 expression and several clinical and pathological aspects of OSCC, their relationship with p53 and HPV, as well as genetic alterations in their expression pattern, their use as a prognosis marker in the evolution of precancerous lesions and their roles in anticancer treatments.The results of p21WAF1/CIP1 expression in OSCC showed mixed results in terms of positivity/negativity among different studies; although all agree that expression is entirely nuclear, unlike other CDKIs such as p16, in which nuclear/cytoplasm location results are variable -10. In  As for p21 expression and its relationship with cell cycle control, Neves Ada et al. , found nRegarding the relationship with clinical-pathological parameters, the results are highly variable, thus Fillies et al.  accounteOther authors found no relationship between p21 expression and the clinical-pathological variables under study ,25. OsakAs mentioned above, p21 is regulated in two different ways; either through a p53-dependent pathway or a p53-independent one, so it is very important to establish the relationship between these two proteins in OSCC.For van Oijen et al.  and NemeIn this regard, Brennan et al. , found tNg et al.  found noIf we address p53/p21 status and its relationship with clinical-pathological parameters, according to Kapranos et al.  the diseIn the dysplastic epithelium, p21 increases its expression as the degree of dysplasia increases. In OSCC, expression is variable, especially in poorly differentiated tumor areas. They found no association whatsoever with any clinical-pathological feature. Agarwal et al. , found aAs regards to the detection of HPV in OSCC and the expression of cell-cycle proteins, it seems that the E7 oncoprotein in high-risk HPV causes cell cycle dysregulation through the interaction of AP-1 complex transcription and CDKIs such as p27 and p21. Soares et al. , found tAs regards to the genetic alterations of p21 in OSCC, Ralhan et al. , describThe frequency of mutations (transitions and transversions) in exon 2 of p21, according to Ibrahim et al. , ranges The induction of differentiation and anticancer agents remains today as the most appropriate strategy in cancer treatments, although in clinical practice results are insufficient. The mechanism of action of these molecules and agents in relation to p21 is not fully understood. According to Yoneda et al. , vesnariThe mechanism of action of 5-FU (5-fluorouracil) and γ-rays, consists of an apoptotic effect of tumor cells yet in a p53 and p21 independent manner. According to Yoneda et al. , althougThese same results, in which there is an increase in p21 expression with cell-cycle blockage, have been described for perifosine  , phenoxodial (a new isoflavone), EGCG , SFN (sulforaphane) and also for cyclosporine A, growth inhibitory doses of EGF and X radiation .As we have seen, the role of p21WAF1/CIP1 as cell-cycle regulator has been well described; however, its relationship to OSCC, clinical and pathological variables of the tumors, HPV and different treatment modalities are not entirely clear. Thus, it would be very interesting to pursue further study of this protein, which may have a significant value in terms of diagnosis, prognosis and therapy in this type of tumors.


Mycobacterium marinum causes skin and soft tissue, bone and joint, and rare disseminated infections. In this study, we aimed to investigate the relationship between treatment outcome and antimicrobial susceptibility patterns. A total of 27 patients with M. marinum infections were enrolled.Data on clinical characteristics and therapeutic methods were collected and analyzed. We also determined the minimum inhibitory concentrations of 7 antibiotics against 30 isolates from these patients.p = 0.0297), and rifampicin  treatment in the cured patients was longer than that in the others. Surgical debridement was performed in 10 out of the 18 cured patients, and in 1 of another group (p = 0.0417). All the 30 isolates were susceptible to clarithromycin, amikacin, and linezolid; 29 (96.7%) were susceptible to ethambutol; 28 (93.3%) were susceptible to sulfamethoxazole; and 26 (86.7%) were susceptible to rifampicin. However, only 1 (3.3%) isolate was susceptible to doxycycline.Twenty-seven patients received antimycobacterial agents with or without surgical debridement. Eighteen patients were cured, 8 failed to respond to treatment, and one was lost to follow-up. The duration of clarithromycin (147 vs. 28; Early diagnosis of the infection and appropriate antimicrobial therapy with surgical debridement are the mainstays of successful treatment. Clarithromycin and rifampin are supposed to be more effective agents. Mycobacterium marinum is a Runyon group I, slow-growing mycobacterium with an optimal growth temperature of 30°C M. marinum infections. These include prescription of local or systemic steroids or immunosuppressive agents, and structural lung diseases. Among these, the primary risk factor is exposure to aquatic environments or marine animals. Thus, M. marinum infection is also known as “fish tank granuloma” M. marinum infections are tetracycline, doxycycline (DOX), clarithromycin (CLR), and rifampicin (RIF) plus ethambutol (EMB) M. marinum infections; in addition, some unsatisfactory results were encountered with the available regimens M. marinum infection, evaluate the treatment benefits, and analyze factors influencing the treatment outcome.Currently, the most common regimens used for treating The study was approved by the Institutional Review Board of the Chang Gung Memorial Hospital Linkou Medical Center in December, 2009. Patients were requested to give written informed consent to store and use the data. No linkage of these data with other sources was done. No patient identifiers were included in the dataset used for this analysis. All bacterial strains were obtained from the Bacteria Bank, Department of Laboratory Medicine, Chang Gung Memorial Hospital.M. marinum infection. We studied the records of 27 patients who were enrolled for treatment at at the Chang Gung Memorial Hospital, Taiwan between January 1, 1999 and December 31, 2010. We retrospectively analyze the patients' medical charts for demographic data, contact history, infection sites, comorbidities, histological results, antimycobacterial regimens, surgical history, and outcomes. Among the 27 patients, 24 had either skin or soft-tissue infections, 1 had arthritis, 1 had a corneal infection, and 1 had a pulmonary infection. Twenty-six patients received antimycobacterial therapy, and 1 patient received steroid inhalation therapy, because this patient was treated as hypersensitivity pneumonitis; 10 of these 27 patients underwent at least 1 episode of surgical debridement. The antimycobacterial regimens included the following: RIF 600 mg/day , EMB 1200 mg/day , CLR 500 mg twice a day, DOX 100 mg twice a day, co-trimoxazole (sulfamethoxazole-trimethoprim) (SXT) 800/160 mg twice a day, and amikacin (AMK) 7.5 mg/kg twice a day. The clinical outcomes were classified as follows: (i) successful: remission of lesions without any sequelae; (ii) unsuccessful: persistent symptoms and signs of infection, relapse, or recurrence of infection within 6 months after completion of therapy, or who was lost to follow-up.A subject was defined as a patient if he/she had a culture-positive M. marinum isolates were collected. We isolated 3 strains from 1 patient, 2 strains from another, and 1 strain each from the remaining 25 patients. Bacteria were identified by traditional culture and biochemical methods hsp65 gene polymorphism analysis was performed to confirm the identification of M. marinum, as described by Telenti et al. M. marinum ATCC 927 was purchased from the American Type Cell Collection organization.A total of 30 We followed the procedure described by Kent and Kubica M. marinum were studied by a microdilution assay, according to the methods described by Wallace and Brown et al. −4 L drug-containing broth. The final bacterial inocula had concentrations between 106 and 107 CFU/L. A 10−5 L bacterial suspension in Middlebrook solution that contained between 10 and 102 CFU was dispensed into each well, including the negative control wells. The following antibiotics were tested: RIF, EMB, CLR, AMK, sulfamethoxazole (SMX), linezolid (LZD), and DOX. CLR was provided by the Pharmaceutical Products Division, Abbott Laboratories, North Chicago, Ill., USA, and LZD was provided by Pfizer Inc., New York, N.Y., USA. The other antimicrobials were purchased from Sigma Chemical Co., St. Louis, Mo., USA. The MIC was determined as the antibiotic concentration of the last well that showed no microbial growth from a series of dilutions of the antibiotic in a 96-well plate. The exception was SMX, for which the end-point was the well with approximately 80% growth inhibition compared with the growth in the negative control well. Susceptibility and resistance breakpoints of M. marinum strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) standards The minimal inhibitory concentrations (MIC) of several antibiotics against U test was used for inter-group comparisons of continuous variables. Categorical variables were compared using the χ2 test or Fisher's exact test as appropriate. A p-value of <0.05 was considered statistically significant.Statistical analyses were performed using STATA version 11 . The Mann–Whitney M. marinum infections. According to the previously described criteria for clinical outcomes, 18 patients' outcomes were defined as successful, and 9 were unsuccessful. As shown in In this study, we enrolled 27 patients who showed culture-positive One patient had a right corneal lesion after a hook injury when finshing shrimps, and another patient had a rare lung infection during combination ribavirin and pegylated interferon therapy for her chronic C hepatitis.These patients did not consult a doctor until the symptoms worsened; the duration from the onset of symptoms to visiting a doctor varied from 15 days to as long as 3 years. The most common presentations were tender, erythematous nodules or plaques (18/27). Seven of the 27 patients presented with ulcerative wounds with a purulent discharge . One of Of the 27 acid-fast stained pus and tissue specimens, 9 (33.3%) were positive. Of these 5, 3, and 1 specimens scored 1+, 2+, 3+, respectively; 3 specimens had no AFS documentation. Samples from 23 patients were subjected to both histopathological examinations and bacterial culturing, while samples from 4 other patients underwent only culture. The most commonly documented pathological condition was suppurative granulomatous inflammation (8/23), followed by granulomatous inflammation (7/23), caseating granulomatous inflammation (2/23), and necrotizing granulomatous inflammation (2/23). Four specimens were reported to indicate chronic inflammation, rheumatoid nodule, focal alveolar damage, and corneal ulcer.M. marinum ATCC 927) was susceptible to all 7 drugs. The results of in vitro susceptibility testing indicated that M. marinum isolates were basically sensitive to the drugs used in the test, with a sensitivity rate ranging between 86.7% (RIF) to 100% ; the only exception was DOX, to which only 1 (3.3%) isolate was sensitive ; and RIF, 201 (154–247) vs. 91 (21–134) (p = 0.0266). These figures indicate that the duration of prescription of CLR, and RIF was longer in the successful group than in the unsuccessful group. On the other hand, the median (IQR) duration of prescription for DOX was 50.5 (28–73) vs. 18 (12–21) (p = 0.0507) in the successful versus unsuccessful group , respectively. This indicated there is a tendency to treatment failure for prescription of doxycycline. Furthermore, the median (IQR) duration of prescription of the following antibiotics in the successful versus unsuccessful groups was as follows: isoniazid (INH), 191 (73–226) vs. 91 (p = 0.5102); EMB, 220 (154–247) vs. 91 (p = 0.1724); SXT, 52.5 (28–77) vs. 16 (14–18) (p = 0.1213); ciprofloxacin (CIP), 70.5 (22–119) vs. 21 (15–143) (p = 0.5637); and erythromycin, 134, respectively. Besides, 10 patients in the successful group had received surgical debridement; whereas, only 1 patient in the unsuccessful group had received surgical debridement .For antimicrobial therapy, the median (IQR) duration of prescription (in days) for each antibiotic in the successful versus unsuccessful groups was as follows: CLR, 147 (91–281) vs. 28 (21–35)  had successful results . In addiM. marinum infection remains a challenge. One of the reasons that make diagnosis difficult is the patients' lack of awareness coupled with the fact that M. marinum infections progress slowly, with a median (IQR) progression time of 3 (1–6) months. As the patients did not consult the doctor until the clinical symptoms worsened, it was difficult to identify the relationship between M. marinum skin infections and previous trauma history. Besides, cutaneous lesions are generally nonspecific and are often initially misdiagnosed as pyoderma, furunculosis, or even sporotrichosis M. marinum infections are usually treated empirically with antituberculosis agents, and antibiotic-susceptibility testing is not routinely performed in many clinical laboratories. These issues make the treatment of M. marinum even more difficult. The results of this study presented the antibiotic susceptibility pattern of M. marinum and characterized the relationship between antimicrobial therapy, surgery, and treatment outcome in M. marinum infections in Taiwan. These results may thus be used as a reference for clinical treatment of M. marinum infections in other countries.Efficiently treatment of in vitro susceptibility in this study showed a high susceptibility rate (>90%) for CLR, LZD, AMK, or SMX, which was consistent with effective treatment results. It is suggested that each single agent can be considered for treating in superficial M. marinum infections. From the viewpoint of pharmacokinetics, LZD could be a good alternative oral agent, although there have been no clinical trials till date to support this hypothesis M. marinum infection with DOX or minocycline M. marinum strains showed only 3.3% (1/30) sensitivity to DOX. This may reflect the high rate of treatment failure encountered in our patients treated with DOX. The controversy over DOX therapy may be related to the regional drug resistance pattern of M. marinum. Thus, it is suggested that drug susceptibility testing of M. marinum should be performed in patients whose treatment has failed and also in regions where the drug-resistance rate is high.The CLSI report does not recommend routine susceptibility testing of this species. However, the test may be necessary for some patients whose samples are still culture positive after receiving several months of unsuccessful therapy M. marinum infections include delayed diagnosis and ineffective regimens in antimicrobial therapy. To date, there have been no comparative trials for treatment regimens in M. marinum skin and soft-tissue infections. A general approach is to treat patients with 2 active agents for 1–2 months after resolution of symptoms; the total treatment time is typically 3–4 months The potential reasons for the treatment failure/difficulty in M. marinum infections, a rare case involving a pulmonary infection was observed. The patient was a middle-aged woman and received interferon and ribavirin therapy for chronic hepatitis C. She then acquired interstitial pneumonitis where the M. marinum strain was isolated. This strain was sensitive to all tested antibiotics except DOX. Due to the delayed diagnosis and the lack of antimicrobial therapy, she developed sequelae such as pulmonary fibrosis and rheumatoid arthritis-like disorders. In 2005, Lai et al. also reported a case of pulmonary infection in an immunocompetent patient M. marinum causes superficial infections, in addition to disseminated or even pulmonary infections. It would be worth monitoring and investigating this phenomenon closely for a longer duration.Among M. marinum infection. In contrast, DOX prescription is not suitable for this purpose.In conclusion, optimal antimicrobial therapy consisting of CLR and/or RIF plus ethambutol, and surgical debridement may have a high treatment success rate in


Klebsiella pneumoniae bloodstream infection (KpBSI).Healthcare-associated (HCA) infection has emerged as a new epidemiological category. The aim of this study was to evaluate the impact of HCA infection on mortality in community-onset KpBSI within 48 hours of admission were enrolled. We compared the clinical characteristics of HCA and community-acquired (CA) infection, and analyzed risk factors for mortality in patients with community-onset KpBSI.We conducted a retrospective study in two tertiary-care hospitals over a 6-year period. All adult patients with KpBSI, 313 (57%) were classified as HCA- KpBSI and 240 (43%) as CA-KpBSI. In patients with HCA-KpBSI, the severity of the underlying diseases was higher than in patients with CA-KpBSI. Overall the most common site of infection was the pancreatobiliary tract. Liver abscess was more common in CA-KpBSI, whereas peritonitis and primary bacteremia were more common in HCA-KpBSI. Isolates not susceptible to extended-spectrum cephalosporin were more common in HCA- KpBSI than in CA-KpBSI . Overall 30-day mortality rate was significantly higher in HCA-KpBSI than in CA-KpBSI . In multivariate analysis, high Charlson’s weighted index of co-morbidity, high Pitt bacteremia score, neutropenia, polymicrobial infection and inappropriate empirical antimicrobial therapy were significant risk factors for 30-day mortality.Of 553 patients with community-onset KpBSI in community-onset KpBSI has distinctive characteristics and has a poorer prognosis than CA-KpBSI, but HCA infection was not an independent risk factor for 30-day mortality.HCA- S. aureus dominating the research, and these studies reported inconsistent data concerning the impact of HCA infection on mortality [Within the last decade, the concept of healthcare-associated (HCA) infection has been introduced, and HCA infection has been described as an epidemiological category different from both community-acquired (CA) and nosocomial infection ,2. Most ortality -13. For ortality -12.Klebsiella pneumoniae is one of the most important gram-negative bacteria clinically, and K. pneumoniae bloodstream infection (KpBSI) has a mortality rate of about 20% [KpBSI was simply classified into CA and nosocomial infections depending on bacteremia onset time: within 48 hours and after 48 hours of admission, respectively, and the different characteristics of CA-KpBSI versus nosocomial KpBSI have been well evaluated [KpBSI is usually associated with liver abscesses in patients with diabetes in East Asian countries, such as Korea and Taiwan [KpBSI presents as primary bacteremia and/or pneumonia in patients with severe underlying diseases like malignancies. Thus, nosocomial infection has a higher mortality than CA infection [KpBSI [KpBSI.bout 20% ,14-16. Cvaluated ,17,18. Cd Taiwan -22. On tnfection ,17,18. Hn [KpBSI -13. TherKpBSI from January 2003 to December 2008 at Seoul National University Hospital  and Seoul National University Bundang Hospital . All adult patients (≥18 year) who had KpBSI within 48 hours of admission were enrolled. When there were multiple KpBSI episodes only the first was included. We collected patient’s data on age, sex, underlying disease, site of infection, laboratory findings, microbiologic characteristics and treatment outcomes. To assess treatment outcomes we investigated 30-day mortality. This study was approved by the institutional review board of Seoul National University Hospital (IRB No. H-1010-062-336) and Seoul National University Bundang Hospital (IRB No. B-0910/086-004) according to the Helsinki Declaration.We conducted a retrospective study of the medical records of the patients with KpBSI was defined as KpBSI occurring within 48 hours of admission. HCA-KpBSI was defined when a patient had one of the following medical histories: (1) intravenous therapy at home or in an outpatient clinic within the previous 30 days; (2) renal dialysis in a hospital or clinic within the previous 30 days; (3) hospitalization for 2 or more days within the previous 90 days; (4) residence in a nursing home or long-term care facility for 2 or more days [KpBSI.Community-onset stories:  intravenK. pneumoniae was isolated from blood culture at the same time as the K. pneumoniae, and the isolated pathogen also had clinical significance. Infection focus was assessed clinically by attending physician in accordance with site of isolation of K. pneumoniae.Biliary tract disease was defined when one or more complicated biliary stone was present, or there was a structural biliary abnormality due to benign or malignant disease. Chronic liver disease referred to chronic hepatitis and liver cirrhosis due to any cause. Charlson’s weighted index of co-morbidity and the Pitt bacteremia score were used to evaluate the severities of underlying disease and of acute illness, respectively ,24. ShocK. pneumoniae which was not susceptible to either cefotaxime or ceftazidime was considered as ‘suspected extended-spectrum beta-lactamase (ESBL) producing K. pneumoniae’. Antimicrobial therapy was considered as ‘inappropriate’ when the treatment regimen did not include any antibiotic active in vitro. In addition 3rd generation cephalosporin monotherapy for ‘suspected ESBL-producing K. pneumoniae’ was considered ‘inappropriate’, regardless of the results of antibiotic susceptibility tests.The empirical antimicrobial therapy was defined as the initial antibiotic choice before the results of blood culture and antimicrobial susceptibility tests were available, and the definitive antimicrobial therapy was defined as the antibiotic choice after the report of microbiologic tests. K. pneumoniae’ isolates, ESBL production was determined by the double disk synergy test according to the CLSI performance standards [All isolates were defined by BacT/ALERT FA and FN . Antimicrobial susceptibility was identified by disk diffusion tests from 2003 to 2006, and by Microscan WalkAway-96  from 2007 to 2008, using the criteria of the Clinical and Laboratory Standards Institute  guidelines. For the available ‘suspected ESBL-producing tandards .t-test was used to compare continuous variables and the χ2 test or Fisher’s exact test was used to compare categorical variables. To identify independent risk factors for 30-day mortality, a stepwise logistic regression model was used. Risk factors with a p value <0.10 in the univariate analysis for 30-day mortality were included in the initial model, and forward stepwise selection was performed to develop the final model. We included the Pitt bacteremia score instead of shock and, the Charlson’s weighted index of co-morbidity instead of underlying diseases to avoid data overlap in the multivariate analysis. p <0.05 was considered statistically significant. PASW for Windows  was used for all analyses.Student’s KpBSI were identified in the 6-year period. Of these, 553 (93%) were analyzed, because 34 patients were lost to follow-up and medical record was not available in 5 patients. Of the 553 patients with community-onset KpBSI, 313 (57%) were classified as HCA-KpBSI and 240 (43%) as CA-KpBSI. The mean age of the 553 patients was 61 years , and 348 (63%) of the patients were male. Solid tumor was the most common underlying disease . 145 (26%) patients had diabetes mellitus and 123 (22%) had chronic liver disease.592 patients with community-onset KpBSI and CA-KpBSI are listed in Table . 24%; p <0.001), hematologic malignancy  and chronic liver disease  were more common in HCA-KpBSI than in CA-KpBSI. Diabetes mellitus  was more common in CA-KpBSI than in HCA-KpBSI.The demographics and underlying diseases of HCA-The pancreatobiliary tract was the most common site of infection . Liver  and primary bacteremia (unknown focus)  were also frequent sites of infection. Initially 156 (28%) patients presented shock and 45 (8%) had neutropenia. 40 (7%) patients of the 553 patients were treated with inappropriate empirical antimicrobial therapy. After excluding 52 of the 553 patients , 14 of the remaining 501 patients (3%) were found to have been treated with inappropriate definitive antimicrobial therapy.KpBSI and CA-KpBSI are also compared in Table . 5%; p <0.001) and primary bacteremia  were more common in HCA-KpBSI than in CA-KpBSI. On the other hand, liver abscess  was more frequent in CA-KpBSI than in HCA-KpBSI. Initial shock  and neutropenia  were more common in HCA-KpBSI than in CA-KpBSI. The 30-day mortality of HCA-KpBSI was higher than that of CA-KpBSI .The primary sites of infection and treatment outcomes of HCA-KpBSI and CA-KpBSI are compared in Table KpBSI than of the CA-KpBSI was resistant to tested antimicrobial agents other than imipenem and amikacin.48 of the 553 isolates (9%) were not susceptible to ciprofloxacin and 37 isolates (7%) were not susceptible to either cefotaxime or ceftazidime. Of these 37 isolates, 27 were available for ESBL confirmatory tests and we performed the double disk synergy test on them. Eighteen were confirmed as producing ESBL. The antimicrobial susceptibilities of HCA-p = 0.440) and extended-spectrum cephalosporin  between survivors and non-survivors.The results of the univariate analyses of risk factors for 30-day mortality are shown in Table From the multivariate logistic regression analysis, significant risk factors for 30-day mortality were high (≥3) Charlson’s weighted index of co-morbidity , high ≥4) Pitt bacteremia score , neutropenia , polymicrobial infection  and inappropriate empirical antimicrobial therapy . Liver abscess  and pancreatobiliary tract infection  were found to be protective factors  in the present study. The latter finding is similar to that of a study performed in Taiwan, although in the Taiwanese study the difference was not statistically significant  [Cancer was the most common associated condition in HCA-al KpBSI , it was = 0.339) .KpBSI. The most common source was the pancreatobiliary tract (33%), followed by liver abscess (20%). Liver abscess was more frequent in CA-KpBSI than in HCA-KpBSI. Compared to nosocomial KpBSI, in which liver abscess was very rare (0% to 2%) [KpBSI was quite frequently associated with liver abscess (13%). Peritonitis was fairly frequent (>10%), more so in HCA-KpBSI than in CA-KpBSI in our analysis; in contrast Wu et al. found only a few (<5%) of intra-abdominal infection and no difference in frequency between HCA-KpBSI and CA-KpBSI [The primary site of infection was identified in 87% of community-onset % to 2%) ,14,18, HCA-KpBSI . Our higCA-KpBSI ,28.KpBSI isolates than of the CA-KpBSI isolates were resistant to antimicrobial agents. Over 10% of the former were not susceptible to ciprofloxacin and 9% were not susceptible to one of the extended-spectrum cephalosporin. Although frequent antimicrobial resistance could affect the inadequacy of the initial choice of antimicrobial agent, there was no difference in rate of inappropriate empirical antimicrobial therapy between the HCA-KpBSI and the CA-KpBSI . This result could have arisen because in cases of healthcare-associated infection clinicians may have taken into account frequencies of antimicrobial resistance when selecting the initial antibiotic. Actually, fewer HCA-KpBSI than CA-KpBSI  were started on quinolones while more were started on piperacillin-tazobactam . Considering that only 3.3% of organisms in CA infection and 9.3% of organisms in HCA infection were non-susceptible to extended-spectrum cephalosporins, the use of broad-spectrum antimicrobial agents also might have influenced the lower proportion of patients with treated inappropriately. However, other East Asian studies of K. pneumoniae bacteremia also demonstrated a similar proportion of patients treated with inappropriate empirical therapy [Regarding empirical treatment, the proportion of patients treated inappropriately  was much lower than was observed in other studies, which showed that over 20% of patients were treated inappropriately ,29,30. T therapy ,14,18.KpBSI and CA-KpBSI in this study . High Charlson’s weighted index of co-morbidity (≥3), high Pitt bacteremia score (≥4), neutropenia, polymicrobial infection and inappropriate empirical antimicrobial therapy were found to be independent risk factors for mortality. However, HCA infection itself was not a significant risk factor for 30-day mortality in multivariate analysis. This finding is consistent with the recent report from Taiwan and a bloodstream infection study dealing with gram-negative bacteria [et al., the definition of HCA infection which we used in this study may have been excessively broad since the definition was based on the U.S. medical system [There was a significant difference of 30-day mortality rate between HCA-bacteria ,12. Therbacteria ,24,34. Sbacteria . Liver abacteria ,18. ThirKpBSI and HCA-KpBSI groups. Hence, we cannot extrapolate our result to community-based institutions. Third, we did not evaluate the ‘attributable’ mortality due to KpBSI, so that some of the deaths in our study may not have been related to KpBSI. However, efforts to designate outcomes as ‘attributable’ to infection are often subjective and inconsistent. We therefore employed an unambiguous definition, namely 30-day mortality rate, for evaluating treatment outcomes. Fourth, because we did not review the patients’ previous exposure to antimicrobial agents, we could not determine the influence of that factor on the acquiring resistant organisms and treatment outcome. Additionally, we did not collect data on the variation of antimicrobial therapy, such as duration or dosage; therefore, we could not take into account these issues, which could affect the analysis of risk factors for mortality. However, upon examining the mortality rate in other studies, our data are comparable; therefore, the regimen and duration of therapy we used were also likely to be similar to others [Our study had several limitations. First, there was a potential bias because it was performed retrospectively. Second, it was conducted in tertiary-care and university-affiliated hospitals and there was a large proportion of cancer patients in both the CA-o others ,14.KpBSI. Finally, even though we showed many differences between HCA infection and CA infection, we did not find HCA infection to be an independent risk factor for mortality in KpBSI, which confirmed that the already known risk factors for mortality  are more important predictors of mortality in KpBSI [What clinicians actually want to know is that HCA infection needs a specific work-up process or treatment. Accordingly, our study can provide useful information. First, we could see the difference of infection focus according to the epidemiological category more clearly by separating HCA infection and CA infection in comparison to our previous report . Peritonin KpBSI ,14.KpBSI represented over half of community-onset KpBSI and had different characteristics from CA-KpBSI. In HCA-KpBSI, underlying diseases were more severe, primary bacteremia and peritonitis were more common and resistance to antimicrobials was more frequent than in CA-KpBSI. HCA-KpBSI had higher 30-day mortality than CA-KpBSI, but HCA infection was not an independent risk factor for 30-day mortality. In present-day clinical circumstances, HCA-KpBSI should be identified as a distinctive category and be approached in a different way from CA-KpBSI.HCA-There are no potential conflicts of interest for any authors.All authors conceived of the study. YHJ, MJL, HYS collected the data. KHS and YHJ carried out data analysis and interpretation. NHK, JHH, JYP, PGC, WBP, ESK, SWP, KUP, HBK, NJK, ECK and MDO carried out data interpretation. YHJ and KHS drafted the manuscript. All authors have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/12/239/prepub


Research suggests that, like near-hand effects, visual targets appearing near the tip of a hand-held real or virtual tool are treated differently than other targets. This paper reviews neurological and behavioral evidence relevant to near-tool effects and describes how the effect varies with the functional properties of the tool and the knowledge of the participant. In particular, the paper proposes that motor knowledge plays a key role in the appearance of near-tool effects. One of the most surprising and interesting findings in research on near-hand effects is the possibility that they may also apply to the functional end of hand-held tools and virtual tools. Perhaps one of the reasons tool-users behave as if the tool is a part of their body is that the same neural mechanism responsible for signaling the visual and tactile border-zone between our bodies and surrounding space adapts to code the space surrounding tools. So when an experienced hockey player carries the puck up the ice on his stick, it is possible that his brain responds to visual and tactile information about the puck as if he were carrying it in his hands.The space within reach, known as peripersonal space, is represented by visual-tactile bimodal neurons. Bimodal neurons, discovered in the monkey ventral premotor cortex (PMv), putamen, and the intraparietal sulcus, have overlapping visual and tactile receptive fields , typically on the face or hand  has been demonstrated in a series of studies study conducted by Farnè and his colleagues  to locations in space beyond the body . Put differently, we may need to be able to control and reliably predict the tool's actions before changes in how space around the tool is represented can be implemented . Although not explicitly linked to motor knowledge This view is supported by work showing that near-tool effects can be directly linked to action preparation (Collins et al., A strong prediction of the motor knowledge hypothesis is that when participants are given a tool that is unfamiliar in terms of either inertial, spatial, or temporal dynamics, they will not show enhanced processing near that tool until its dynamics can be predicted in a way that the sensorimotor system finds useful. Brown et al.  tested tThe proposal that motor knowledge plays a key role in near-tool effects can also account for studies showing that near-tool effects can be detected with little or no training. For example, Holmes et al.  reportedThere has also been a great deal of interest in the role that multisensory systems and the motor system may be playing in our ability to treat virtual tools as if they are extensions of ourselves. In this domain, there has been emphasis on the idea that mechanisms involved in defining peripersonal space can extend to virtual tools (e.g., Bassolino et al., Together, these results indicate that motor knowledge about the inertial and spatial dynamics of a tool play an important role in near-tool effects. When people are presented with standard tools, like wooden pointers, or with light easy-to-manipulate tools, like toy rakes, they are able to acquire or recall motor control information quickly. When the system is challenged by presenting participants with tools with novel inertial dynamics or with unusual spatial mappings, the dependence of near-tool effects on motor knowledge is more easily revealed. We may need to be able to control and reliably predict the tool's actions before changes in which the space around the tool is represented can be implemented in any sensory modality. This principle suggests that the future application of near-tool effects in occupational, educational, or rehabilitation settings will require close attention to the role of motor knowledge in tool use—and by extension its role in promoting the detection of stimuli around the “business-end” of tools.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Macrophages play crucial roles in HIV/AIDS pathogenesis as they are important targets for HIV-1 replication and contribute to viral spread and viral reservoir formation. We have previously reported that p21 inhibits HIV-1, HIV-2 and SIV replication in macrophages by a major block at the level of reverse transcription [Monocyte-derived macrophages (MDM) were differentiated from monocytes isolated from healthy donor blood with human AB serum.The induction of p21 expression levels was obtained by the stimulation of MDM by the immobilized immunoglobulins (IVIg). MDM were infected with NL4.3-Luc HIV-1 pseudotyped with VSV-G or replication-competent SIVmac251. HIV-1 and SIV late reverse transcripts were quantified by Taqman quantitative real-time PCR (qRT-PCR). p21, RNR2, E2F1 and RB knockdowns were obtained by small interfering RNAs (siRNAs) transfection of MDM. Silencing efficiencies were determined by qRT-PCR mRNA quantification and by western blot. Intracellular dNTP concentrations were measured by a single-nucleotide incorporation assay. Statistical analyses were performed with the Kruskal-Wallis and the Mann-Whitney tests.Through overexpression and knockdown experiments in primary monocyte derived macrophages, we demonstrated that p21 inhibits HIV-1 reverse transcription by down-regulating the intracellular dATP and dTTP pools available for viral cDNA synthesis. We found that p21 represses the expression of ribonucleotide reductase subunit R2 (RNR2), an enzyme indispensable for dNTP biosynthesis. Accordingly, depletion of RNR2 either by p21 induction or RNR2-specific siRNA transfection inhibits reverse transcription of HIV-1 in macrophages. Noteworthy, p21 induction and RNR2 knockdown also restrict SIVmac251 in macrophages, in spite of Vpx-mediated degradation of SAMHD1.We further explored the mechanisms underlying the inhibition of RNR2 expression by p21 and found that p21 represses the expression of the RNR2 transcriptional transactivator E2F1, independently from the Retinoblastoma protein RB. Consistently, the depletion of E2F1 by p21 induction or E2F1-specific siRNA transfection represses RNR2 transcription and inhibits HIV-1 reverse transcription in macrophages.Here we describe a new mechanism of restriction of lentiviral replication in macrophages: p21 inhibits HIV-1 reverse transcription by affecting dNTP biosynthesis through repression of RNR2 expression differently from SAMHD1 restriction that promotes dNTP catabolism. Accordingly, p21 restricts other primate lentiviruses able to escape SAMHD1 restriction through Vpx, such as HIV-2 and SIV Our findings describe a novel metabolic pathway of HIV-1 restriction in macrophages and open on new potential cellular targets for therapy research.


Medical educators and patients are turning to YouTube to teach and learn about medical conditions. These videos are from authors whose credibility cannot be verified & are not peer reviewed. As a result, studies that have analyzed the educational content of YouTube have reported dismal results. These studies have been unable to exclude videos created by questionable sources and for non-educational purposes. We hypothesize that medical education YouTube videos, authored by credible sources, are of high educational value and appropriately suited to educate the public. Credible videos about cardiovascular diseases were identified using the Mayo Clinic's Center for Social Media Health network. Content in each video was assessed by the presence/absence of 7 factors. Each video was also evaluated for understandability using the Suitability Assessment of Materials (SAM). User engagement measurements were obtained for each video. A total of 607 videos (35 hours) were analyzed. Half of all videos contained 3 educational factors: treatment, screening, or prevention. There was no difference between the number of educational factors present & any user engagement measurement (p NS). SAM scores were higher in videos whose content discussed more educational factors (p<0.0001). However, none of the user engagement measurements correlated with higher SAM scores. Videos with greater educational content are more suitable for patient education but unable to engage users more than lower quality videos. It is unclear if the notion “content is king” applies to medical videos authored by credible organizations for the purposes of patient education on YouTube. In recent years medical educators and patients are increasingly turning to YouTube to teach and learn about medical conditions, respectively. Although the creators of YouTube designed it for entertainment, rather than educational, purposes, users are producing and viewing videos about topics such as immunizations, prostate cancer, and kidney stones in greater numbers. This dilution is evident in the published scientific literature. Since 2007, investigations have reported dismal results regarding the educational content of YouTube http://network.socialmedia.mayoclinic.org). Healthcare organizations, located within United States and committed to patient education, comprise this network We defined credible videos and YouTube channels as those authored by organizations that have a publicly stated commitment towards patient education. We identified such organizations by querying the Social Media Health network at the Mayo Clinic Center for Social Media  epidemiology, 2) pathophysiology 3) screening, 4) diagnosis, 5) complications, 6) treatment/management, and 7) prevention. We obtained the definitions for each domain from the fourth edition of the American Heritage Dictionary of English Language or the American Heritage Medical Dictionary. Five authors  assessed the presence or absence of each domain within a particular video. These authors calculated a cumulative integer score between zero (no domains present) to seven  for each video.We performed an inter-rater agreement analysis by using videos that contained information about cardiac, vascular, or cardiovascular diseases, but did not meet the geographic inclusion criteria.We evaluated the degree to which the lay public could understand each video. Previous investigations have used the Suitability Assessment of Materials (SAM), a validated scoring system, to evaluate print-, audio-, and video-formatted patient education materials We recorded five measures of user engagement for each video: the number of 1) video views, 2) likes, 3) dislikes, 4) favorites, and 5) comments. We collected this data from February 6–8, 2013. We quantified the degree of independence for each metric against the other  because no such analysis was found in the medical literature. We defined videos with high user engagement as those with a large number of observations in any independent metric .We defined an optimal video as being both of great educational breadth and of superior suitability. We predefined a video of great educational breadth as one whose content was categorized in at least 4 educational domains. A highly suitable (superior) video, defined by the creators of the SAM scoring system, was any video that scored 70% or greater (raw score 27 or greater). Optimal videos exhibited both properties. We did not use the measures of engagement to identify optimal videos.2 between 0 and 0.55. We considered integer scores, obtained by assessing the educational breadth of content , as ordinal variables. SAM scores were continuous variables. We recorded data on Google Spreadsheets and analyzed data with Microsoft Excel 2007 and JMP 10.1. Appropriate statistical tests are indicated within the body of the text and each table/figure. We defined statistical significance as results with a p value of less than 0.01.We considered video views, duration, and all user engagement metrics as continuous variables. We defined an independent user engagement metric as having a RThis investigation was exempt from Institutional Review Board approval because it focused on publicly available educational material from organizations and not individual patients. We attempted as close adherence to STROBE guidelines as possible Cardiologist speaks on the dangers of K2 at http://youtu.be/Owo-UU_u6Cc) from the analyses because it exhibited outlying tendencies . The remaining 606 videos were of 34.9 hours duration  met inclusion criteria for further analyses . We exclduration . We anal2 0.90) and with the number of video views .We measured user engagement using five metrics. Approximately 80% of all videos contained at least one educational domain . The mosThe median SAM score was 24 (IQR 16 and 28). One-third of the videos were of superior suitability (203 videos) and 45% were adequate. Superior videos had a longer duration than adequate and inadequate videos . There were no statistical differences between any user engagement metric and the suitability of a video .We predefined an “optimal” video as one with 4 or more educational domains and a superior suitability SAM score. In general, videos of great breadth had a higher SAM score than less educational videos . However, there were far fewer optimal videos than all other videos combined . Although optimal videos were the longest videos of any type, they did not engage the user with greater frequency than any other video type .2 0.009).We compared each educational domain against Video Views, Dislikes, and Comments to identify any domain that was disproportionately represented in the videos with high user engagement. Authoritative/credible healthcare organizations produce few highly educational and/or suitable medical videos. Additionally, the general public does not engage with those videos that are 1) highly educational, 2) of superior suitability, or 3) optimal. As a result, we were unable to reject the null hypothesis.We based our hypothesis on the premise that credible organizations would author a large number of optimal videos and that the public would engage with those optimal videos. By eliminating entertainment videos that could have been disguised as educational, we believed that this investigation would uncover the true public response towards medically focused YouTube videos. The Social Media Healthcare network allowed us to capture only those YouTube videos that fulfilled our requirement for accuracy and credibility. Nevertheless, only 27% of videos were of great educational breadth . This percentage is similar to that found by other investigators, including those that have studied videos about prostate cancer (27%) The public had an unfavorable response to optimal videos. Despite fewer optimal videos, the public did not view these videos or provide comments with greater frequency. Previous investigations regarding cardiopulmonary resuscitation or influenza vaccinations showed a similar disconnect between video quality and user engagement Surprisingly, the greatest strength of this investigation did not result in findings that were dissimilar to those of previous investigations. The focus on videos produced by 1) reputable organizations that have 2) committed to publishing accurate medical videos about 3) the leading composite causes of death in the United States did not garner a better public response. Using the Social Media Healthcare network to “drill down” onto credible and accurate medical videos failed to uncover a more positive user experience. Our second strength involves the sample size. Previous investigations analyzed videos numbering between 29 to 199 and a total video duration between 216 to 765 minutes Rescue 911) or YouTube videos authored by reputable healthcare organizations, it is unclear if “content is king” in medical education videos Is content really king? Media experts preach this concept as a key to successfully communicating with the public. In recent years, however, investigations such as ours have yielded data that call this notion into question. Content and quality may be key ingredients for entertainment-focused organizations. When the goal of content is to educate the public, however, healthcare organizations do not produce many optimal videos. When an organization authors an optimal video, the general public is no more likely to engage with it than with less optimal videos. Indeed we cannot predict how the public will engage with a video based on 1) educational breadth, 2) SAM score, and/or 3) publicly available metadata. This uncertainty poses a major challenge to healthcare organizations. Neither a commitment to creating accurate medical videos nor creating videos with great educational breadth or high suitability results in a positive user experience. Thus, whether the content is delivered through medical-based television shows Click here for additional data file.