The complex biology and contribution of Staphylococcus aureus in atopic dermatitis, current and future therapies.

Atopic dermatitis (AD) is a complex, chronic inflammatory skin disorder affecting more than 10% of U.K. children and is a major cause of occupation-related disability. A subset of patients, particularly those with severe AD, are persistently colonized with Staphylococcus aureus and exacerbation of disease is commonly associated with this bacterium by virtue of increased inflammation and allergic sensitization, aggravated by skin barrier defects. Understanding the complex biology of S. aureus is an important factor when developing new drugs to combat infection. Staphylococcus aureus generates exoproteins that enable invasion and dissemination within the host skin but can also damage the skin and activate the host immune system. Antibiotics are often used by dermatologists to aid clearance of S. aureus; however, these are becoming less effective and chronic usage is discouraged with the emergence of multiple antibiotic-resistant strains. New ways to target S. aureus using monoclonal antibodies and vaccines are now being developed. This review will attempt to evaluate the key biology of S. aureus, current treatment of S. aureus infections in AD and recent advances in developing new anti-S. aureus therapies that have potential in severe AD.

Autologous dendritic cells prolong allograft survival through Tmem176b-dependent antigen cross-presentation.

The administration of autologous (recipient-derived) tolerogenic dendritic cells (ATDCs) is under clinical evaluation. However, the molecular mechanisms by which these cells prolong graft survival in a donor-specific manner is unknown. Here, we tested mouse ATDCs for their therapeutic potential in a skin transplantation model. ATDC injection in combination with anti-CD3 treatment induced the accumulation of CD8(+) CD11c(+) T cells and significantly prolonged allograft survival. TMEM176B is an intracellular protein expressed in ATDCs and initially identified in allograft tolerance. We show that Tmem176b(-/-) ATDCs completely failed to trigger both phenomena but recovered their effect when loaded with donor peptides before injection. These results strongly suggested that ATDCs require TMEM176B to cross-present antigens in a tolerogenic fashion. In agreement with this, Tmem176b(-/-) ATDCs specifically failed to cross-present male antigens or ovalbumin to CD8(+) T cells. Finally, we observed that a Tmem176b-dependent cation current controls phagosomal pH, a critical parameter in cross-presentation. Thus, ATDCs require TMEM176B to cross-present donor antigens to induce donor-specific CD8(+) CD11c(+) T cells with regulatory properties and prolong graft survival.

Characterization of geographically distinct bacterial communities associated with coral mucus produced by Acropora spp. and Porites spp.

Acropora and Porites corals are important reef builders in the Indo-Pacific and Caribbean. Bacteria associated with mucus produced by Porites spp. and Acropora spp. from Caribbean (Punta Maroma, Mexico) and Indo-Pacific (Hoga and Sampela, Indonesia) reefs were determined. Analysis of pyrosequencing libraries showed that bacterial communities from Caribbean corals were significantly more diverse (H', 3.18 to 4.25) than their Indonesian counterparts (H', 2.54 to 3.25). Dominant taxa were Gammaproteobacteria, Alphaproteobacteria, Firmicutes, and Cyanobacteria, which varied in relative abundance between coral genera and region. Distinct coral host-specific communities were also found; for example, Clostridiales were dominant on Acropora spp. (at Hoga and the Mexican Caribbean) compared to Porites spp. and seawater. Within the Gammproteobacteria, Halomonas spp. dominated sequence libraries from Porites spp. (49%) and Acropora spp. (5.6%) from the Mexican Caribbean, compared to the corresponding Indonesian coral libraries (<2%). Interestingly, with the exception of Porites spp. from the Mexican Caribbean, there was also a ubiquity of Psychrobacter spp., which dominated Acropora and Porites libraries from Indonesia and Acropora libraries from the Caribbean. In conclusion, there was a dominance of Halomonas spp. (associated with Acropora and Porites [Mexican Caribbean]), Firmicutes (associated with Acropora [Mexican Caribbean] and with Acropora and Porites [Hoga]), and Cyanobacteria (associated with Acropora and Porites [Hoga] and Porites [Sampela]). This is also the first report describing geographically distinct Psychrobacter spp. associated with coral mucus. In addition, the predominance of Clostridiales associated with Acropora spp. provided additional evidence for coral host-specific microorganisms.

The US gun stock: results from the 2004 national firearms survey.

OBJECTIVES: To examine the size and composition of the privately held firearm stock in the US; and to describe demographic patterns of firearm ownership and motivations for ownership. DESIGN, SETTING AND PARTICIPANTS: A nationally representative household telephone survey of 2770 adults aged>or=18 years living in the US, conducted in the spring of 2004. MAIN OUTCOME MEASURE: Responses to questions regarding firearm ownership, the number and types of guns owned, and motivations for ownership. RESULTS: 38% of households and 26% of individuals reported owning at least one firearm. This corresponds to 42 million US households with firearms, and 57 million adult gun owners. 64% of gun owners or 16% of American adults reported owning at least one handgun. Long guns represent 60% of the privately held gun stock. Almost half (48%) of all individual gun owners reported owning>or=4 firearms. Men more often reported firearm ownership, with 45% stating that they personally owned at least one firearm, compared with 11% for women. CONCLUSIONS: The US population continues to contain at least one firearm for every adult, and ownership is becoming increasingly concentrated. Long guns are the most prevalent type of gun in the US but handgun ownership is widespread. Ownership demographic patterns support findings of previous studies.

The association between changes in household firearm ownership and rates of suicide in the United States, 1981-2002.

OBJECTIVE: To explore whether recent declines in household firearm prevalence in the United States were associated with changes in rates of suicide for men, women, and children. METHODS: This time series study compares changes in suicide rates to changes in household firearm prevalence, 1981-2002. Multivariate analyses adjust for age, unemployment, per capita alcohol consumption, and poverty. Regional fixed effects controlled for cross sectional, time invariant differences among the four census regions. Standard errors of parameter estimates are adjusted to account for serial autocorrelation of observations over time. RESULTS: Over the 22 year study period household firearm ownership rates declined across all four regions. In multivariate analyses, each 10% decline in household firearm ownership was associated with significant declines in rates of firearm suicide, 4.2% (95% CI 2.3% to 6.1%) and overall suicide, 2.5% (95% CI 1.4% to 3.6%). Changes in non-firearm suicide were not associated with changes in firearm ownership. The magnitude of the association between changes in household firearm ownership and changes in rates of firearm and overall suicide was greatest for children: for each 10% decline in the percentage of households with firearms and children, the rate of firearm suicide among children 0-19 years of age dropped 8.3% (95% CI 6.1% to 10.5%) and the rate of overall suicide dropped 4.1% (2.3% to 5.9%). CONCLUSION: Changes in household firearm ownership over time are associated with significant changes in rates of suicide for men, women, and children. These findings suggest that reducing availability to firearms in the home may save lives, especially among youth.

Unintentional and undetermined firearm related deaths: a preventable death analysis for three safety devices.

OBJECTIVE: To determine the proportion of unintentional and undetermined firearm related deaths preventable by three safety devices: personalization devices, loaded chamber indicators (LCIs), and magazine safeties. A personalized gun will operate only for an authorized user, a LCI indicates when the gun contains ammunition, and a magazine safety prevents the gun from firing when the ammunition magazine is removed. DESIGN: Information about all unintentional and undetermined firearm deaths from 1991-98 was obtained from the Office of the Chief Medical Examiner for Maryland, and from the Wisconsin Firearm Injury Reporting System for Milwaukee. Data regarding the victim, shooter, weapon, and circumstances were abstracted. Coding rules to classify each death as preventable, possibly preventable, or not preventable by each of the three safety devices were also applied. RESULTS: There were a total of 117 firearm related deaths in our sample, 95 (81%) involving handguns. Forty three deaths (37%) were classified as preventable by a personalized gun, 23 (20%) by a LCI, and five (4%) by a magazine safety. Overall, 52 deaths (44%) were preventable by at least one safety device. Deaths involving children 0-17 (relative risk (RR) 3.3, 95% confidence interval (CI) 2.1 to 5.1) and handguns (RR 8.1, 95% CI 1.2 to 53.5) were more likely to be preventable. Projecting the findings to the entire United States, an estimated 442 deaths might have been prevented in 2000 had all guns been equipped with these safety devices. CONCLUSION: Incorporating safety devices into firearms is an important injury intervention, with the potential to save hundreds of lives each year.

Relationship between licensing, registration, and other gun sales laws and the source state of crime guns.

OBJECTIVE: To determine the association between licensing and registration of firearm sales and an indicator of gun availability to criminals. METHODS: Tracing data on all crime guns recovered in 25 cities in the United States were used to estimate the relationship between state gun law categories and the proportion of crime guns first sold by in-state gun dealers. RESULTS: In cities located in states with both mandatory registration and licensing systems (five cities), a mean of 33.7% of crime guns were first sold by in-state gun dealers, compared with 72.7% in cities that had either registration or licensing but not both (seven cities), and 84.2% in cities without registration or licensing (13 cites). Little of the difference between cities with both licensing and registration and cities with neither licensing nor registration was explained by potential confounders. The share of the population near a city that resides in a neighboring state without licensing or registration laws was negatively associated with the outcome. CONCLUSION: States with registration and licensing systems appear to do a better job than other states of keeping guns initially sold within the state from being recovered in crimes. Proximity to states without these laws, however, may limit their impact.

Effects of Maryland's law banning Saturday night special handguns on crime guns.

OBJECTIVES: To determine the effects of a 1988 Maryland law that banned "Saturday night special" handguns on the types of guns used in crime. To determine if controls on the lawful market for handguns affect the illegal market as well. SETTING: Baltimore, Maryland, and 15 other US cities participating in a crime gun tracing project. METHODS: Cross sectional comparison of the proportion of crime guns that are banned by the Maryland law, comparing Baltimore, MD with 15 other cities outside of Maryland. Multivariate linear regression analysis to determine if observed differences between Baltimore and 15 other cities are explained by demographic or regional differences among the cities rather than Maryland's law. RESULTS: Among crime guns, a gun banned by Maryland's law is more than twice as likely (relative risk (RR) 2.3, 95% confidence interval (CI) 2.0 to 2.5) to be the subject of a crime gun trace request in 15 other cities combined, than in Baltimore. Among homicide guns, a crime especially relevant for public safety, a comparable difference (RR 2.1, 95% CI 1.1 to 4.2) was observed. The proportion of Baltimore's crime guns that are banned is 12 percentage points lower than would be expected based on its demographic and regional characteristics alone. Among crime guns purchased after 1990, a much smaller proportion in Baltimore are banned models than in 15 other cities. CONCLUSIONS: Maryland's law has reduced the use of banned Saturday night specials by criminals in Baltimore. Contrary to the claims of some opponents of gun control laws, regulation of the lawful market for firearms can also affect criminals.

Incidence and distribution of distant metastases from newly diagnosed esophageal carcinoma.

BACKGROUND: It is important to diagnose distant metastases disease in patients with newly diagnosed esophageal carcinoma, so that unwarranted surgery and its attendant risks are avoided. The purpose of this study was to determine (1) the percentage of esophageal cancer patients with distant metastases (M1) at presentation, (2) the locations of these distant metastases, and (3) how the metastases were diagnosed. METHODS: All patients at the University of Michigan Medical Center with newly diagnosed esophageal cancer between 1982 and July, 1993, were identified. Records for these 838 patients were reviewed, and patients were classified as having M0 or M1 disease at presentation. For patients with M1 disease, the locations of distant metastases and the methods of diagnosis were recorded. RESULTS: One hundred forty-seven of 838 (18%) patients had M1 disease. In 110 of 147 (75%) patients, M1 disease was detected before surgery via imaging or physical examination, including 102 of 147 (69%) via chest or abdominal computed tomography (CT). In no case staged as M0 by abdominal and chest CT was M1 disease detected on bone scan or head CT. Distant metastases were most commonly diagnosed in abdominal lymph nodes (45%), followed by liver (35%), lung (20%), cervical/supraclavicular lymph nodes (18%), bone (9%), adrenal (5%), peritoneum (2%), brain (2%), and stomach, pancreas, pleura, skin/body wall, pericardium, and spleen (each 1%). CONCLUSION: A significant percentage of patients with esophageal cancer have M1 disease at presentation. Imaging of the chest and abdomen is an effective method of screening such patients for M1 disease before treatment.

Ultrasound demonstration of tongue motions during suckle feeding.

In this study the authors used ultrasound to demonstrate characteristic internal actions of the tongue during suckling. Its medial portion, into which the genioglossus is inserted, moves in relation to its lateral portions, into which the styloglossus and hyoglossus are inserted. A peristaltic wave of successive inferior and superior displacements moves posteriorly in the medial portion, compressing or 'milking' the nipple and propelling the expressed milk towards the pharynx. The lateral portions of the tongue enclose the nipple and the bolus and serve as reference for the displacements of the medial portion. These observations are related to anatomical studies of the tongue. The coordination pattern of suckle is compared with that of pharyngeal swallow. In instances where suckle and swallow are immediately sequential, the peristalsis which is common to both is continuous in the oral and pharyngeal portions of the food pathway.