Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response.

Small repeat-associated siRNAs (rasiRNAs) mediate silencing of retrotransposons and the Stellate locus. Mutations in the Drosophila rasiRNA pathway genes armitage and aubergine disrupt embryonic axis specification, triggering defects in microtubule polarization as well as asymmetric localization of mRNA and protein determinants in the developing oocyte. Mutations in the ATR/Chk2 DNA damage signal transduction pathway dramatically suppress these axis specification defects, but do not restore retrotransposon or Stellate silencing. Furthermore, rasiRNA pathway mutations lead to germline-specific accumulation of gamma-H2Av foci characteristic of DNA damage. We conclude that rasiRNA-based gene silencing is not required for axis specification, and that the critical developmental function for this pathway is to suppress DNA damage signaling in the germline.

Fatalities associated with the 2009 H1N1 influenza A virus in New York city.

BACKGROUND. When the 2009 H1N1 influenza A virus emerged in the United States, epidemiologic and clinical information about severe and fatal cases was limited. We report the first 47 fatal cases of 2009 H1N1 influenza in New York City. METHODS. The New York City Department of Health and Mental Hygiene conducted enhanced surveillance for hospitalizations and deaths associated with 2009 H1N1 influenza A virus. We collected basic demographic and clinical information for all patients who died and compared abstracted data from medical records for a sample of hospitalized patients who died and hospitalized patients who survived. RESULTS. From 24 April through 1 July 2009, 47 confirmed fatal cases of 2009 H1N1 influenza were reported to the New York City Department of Health and Mental Hygiene. Most decedents (60%) were ages 18-49 years, and only 4% were aged 65 years. Many (79%) had underlying risk conditions for severe seasonal influenza, and 58% were obese according to their body mass index. Thirteen (28%) had evidence of invasive bacterial coinfection. Approximately 50% of the decedents had developed acute respiratory distress syndrome. Among all hospitalized patients, decedents had presented for hospitalization later (median, 3 vs 2 days after illness onset; P < .05) and received oseltamivir later (median, 6.5 vs 3 days; P < .01) than surviving patients. Hospitalized patients who died were less likely to have received oseltamivir within 2 days of hospitalization than hospitalized patients who survived (61% vs 96%; P < .01). CONCLUSIONS. With community-wide transmission of 2009 H1N1 influenza A virus, timely medical care and antiviral therapy should be considered for patients with severe influenza-like illness or with underlying risk conditions for complications from influenza.

Rapid Patient Discharge Contribution to Bed Surge Capacity During a Mass Casualty Incident: Findings From an Exercise With New York City Hospitals.

BACKGROUND: Mass casualty incidents may increase patient volume suddenly and dramatically, requiring hospitals to expeditiously manage bed inventories to release acute care beds for disaster victims. Electronic patient tracking systems combined with unit walk-throughs can identify patients for rapid discharge. The New York City (NYC) Department of Health and Mental Hygiene's 2013 Rapid Patient Discharge Assessment (RPDA) aimed to determine the maximum number of beds NYC hospitals could make available through rapid patient discharge and to characterize discharge barriers. METHODS: Unit representatives identified discharge candidates within normal operations in round 1 and additional discharge candidates during a disaster scenario in round 2. Descriptive statistics were performed. RESULTS: Fifty-five NYC hospitals participated in the RPDA exercise; 45 provided discharge candidate counts in both rounds. Representatives identified 4225 patients through the RPDA: among these, 1138 (26.9%) were already confirmed for discharge; 1854 (43.9%) were round 1 discharge candidates; and 1233 (29.2%) were round 2 discharge candidates. These 4225 patients represented 21.4% of total bed capacity. Frequently reported barriers included missing prescriptions for aftercare or discharge orders. CONCLUSION: The NYC hospitals could implement rapid patient discharge to clear one-fifth of occupied inpatient beds for disaster victims, given they address barriers affecting patients' safe and efficient discharge.

Heterosexual transmission of community-associated methicillin-resistant Staphylococcus aureus.

Heterosexual transmission of community-associated methicillin-resistant Staphylococcus aureus has not been documented. As part of a survey conducted in northern Manhattan, we encountered 3 households in which heterosexual transmission was responsible for new community-associated methicillin-resistant S. aureus infection. The vaginal and inguinal isolates obtained from the sexual partners were USA 300. This report documents an important and previously unrecognized means of community-associated methicillin-resistant S. aureus colonization and transmission for these potentially invasive strains.

Antimicrobial resistance patterns of colonizing flora on nurses' hands in the neonatal intensive care unit.

BACKGROUND: The Centers for Disease Control and Prevention recommends the use of an alcohol-based handrub for health care worker hand hygiene. The purpose of this study was to examine effects of hand hygiene product and skin condition on the antimicrobial resistance patterns of colonizing hand flora among nurses. METHODS: Colonizing hand flora of 119 nurses working in 2 neonatal intensive care units was compared during a 22-month crossover study using alcohol handrub or antiseptic soap. RESULTS: Altogether, 1442 isolates from 834 hand cultures (mean, 7 cultures/nurse) were obtained. In 3 of 9 regression analyses modeling for resistant staphylococcal flora, the use of antiseptic soap was a significant predictor of resistance, and nurses with damaged skin were 2.79 times more likely to carry Staphylococcus warneri isolates resistant to gentamicin. CONCLUSION: Hand hygiene product and skin condition may influence resistance patterns of hand flora of care providers.

Community-associated methicillin-resistant Staphylococcus aureus prevalence: how common is it? A methodological comparison of prevalence ascertainment.

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are becoming increasingly prevalent. There is geographic variation in their reported prevalence across the United States; however, studies reporting on CA-MRSA prevalence also demonstrate great variability in their case-finding methodology. We conducted a study to see how three different methods to ascertain CA-MRSA prevalence would lead to different estimates. METHODS: Different methods were used to identify cases of CA-MRSA colonization and/or infection in New York City. Method 1: retrospective review of clinical and surveillance cultures identified through a hospital computer database. Method 2: prospective collection of surveillance cultures in the same hospital's emergency department. Method 3: prospective collection of surveillance cultures in a community setting. RESULTS: Differing values for CA-MRSA prevalence resulted depending on the method and denominator used. All nares cultures as the denominator led to prevalence estimates of 0.3%-0.6%; all S. aureus as the denominator led to rates of 1.2%-5%; all MRSA as the denominator led to estimates of 5.5%-50%. CONCLUSIONS: A comparison of three methods revealed that variability in case-finding methodologies can lead to different prevalence estimates. Key factors to consider when comparing CA-MRSA rates include the definition of CA-MRSA, choice of denominator, and method and setting of sample collection.

Staphylococcus aureus in the community: colonization versus infection.

BACKGROUND: Antibiotic-resistant Staphylococcus aureus infections have increased dramatically in the community, yet S. aureus nasal colonization has remained stable. The objectives of this study were to determine if S. aureus colonization is a useful proxy measure to study disease transmission and infection in community settings, and to identify potential community reservoirs. METHODOLOGY/PRINCIPAL FINDINGS: Randomly selected households in Northern Manhattan, completed a structured social network questionnaire and provided nasal swabs that were typed by pulsed field gel electrophoresis to identify S. aureus colonizing strains. The main outcome measures were: 1) colonization with S. aureus; and 2) recent serious skin infection. Risk factor analyses were conducted at both the individual and the household levels; logistic regression models identified independent risks for household colonization and infection. RESULTS: 321 surveyed households contained 914 members. The S. aureus prevalence was 25% and MRSA was 0.4%. More than 40% of households were colonized. Recent antibiotic use was the only significant correlate for household colonization (p = .002). Seventy-eight (24%) households reported serious skin infection. In contrast with colonization, five of the six risk factors that increased the risk of skin infection in the household at the univariate level remained independently significant in multivariable analysis: international travel, sports participation, surgery, antibiotic use and towel sharing. S. aureus colonization was not significantly associated with serious skin infection in any analysis. Among multiperson households with more than one person colonized, 50% carried the same strain. CONCLUSIONS/SIGNIFICANCE: The lack of association between S. aureus nasal colonization and serious skin infection underscores the need to explore alternative venues or body sites that may be crucial to transmission. Moreover, the magnitude of colonization and infection within the household suggests that households are an underappreciated and substantial community reservoir.

The Drosophila SDE3 homolog armitage is required for oskar mRNA silencing and embryonic axis specification.

Polarization of the microtubule cytoskeleton during early oogenesis is required to specify the posterior of the Drosophila oocyte, which is essential for asymmetric mRNA localization during mid-oogenesis and for embryonic axis specification. The posterior determinant oskar mRNA is translationally silent until mid-oogenesis. We show that mutations in armitage and three components of the RNAi pathway disrupt oskar mRNA translational silencing, polarization of the microtubule cytoskeleton, and posterior localization of oskar mRNA. armitage encodes a homolog of SDE3, a presumptive RNA helicase involved in posttranscriptional gene silencing (RNAi) in Arabidopsis, and is required for RNAi in Drosophila ovaries. Armitage forms an asymmetric network associated with the polarized microtubule cytoskeleton and is concentrated with translationally silent oskar mRNA in the oocyte. We conclude that RNA silencing is essential for establishment of the cytoskeletal polarity that initiates embryonic axis specification and for translational control of oskar mRNA.

RISC assembly defects in the Drosophila RNAi mutant armitage.

The putative RNA helicase, Armitage (Armi), is required to repress oskar translation in Drosophila oocytes; armi mutant females are sterile and armi mutations disrupt anteroposterior and dorsoventral patterning. Here, we show that armi is required for RNAi. armi mutant male germ cells fail to silence Stellate, a gene regulated endogenously by RNAi, and lysates from armi mutant ovaries are defective for RNAi in vitro. Native gel analysis of protein-siRNA complexes in wild-type and armi mutant ovary lysates suggests that armi mutants support early steps in the RNAi pathway but are defective in the production of active RNA-induced silencing complex (RISC), which mediates target RNA destruction in RNAi. Our results suggest that armi is required for RISC maturation.