Faculty Bibliography

Carbapenem resistance mediated by plasmid-borne Klebsiella pneumoniae carbapenemases (KPC) is an emerging problem of significant clinical importance in Gram-negative bacteria. Multiple KPC gene variants (bla(KPC)) have been reported, with KPC-2 (bla(KPC-2)) and KPC-3 (bla(KPC-3)) associated with epidemic outbreaks in New York City and various international settings. Here, we describe the development of a multiplex real-time PCR assay using molecular beacons (MB-PCR) for rapid and accurate identification of bla(KPC) variants. The assay consists of six molecular beacons and two oligonucleotide primer pairs, allowing for detection and classification of all currently described bla(KPC) variants (bla(KPC-2) to bla(KPC-11)). The MB-PCR detection limit was 5 to 40 DNA copies per reaction and 4 CFU per reaction using laboratory-prepared samples. The MB-PCR probes were highly specific for each bla(KPC) variant, and cross-reactivity was not observed using DNA isolated from several bacterial species. A total of 457 clinical Gram-negative isolates were successfully characterized by our MB-PCR assay, with bla(KPC-3) and bla(KPC-2) identified as the most common types in the New York/New Jersey metropolitan region. The MB-PCR assay described herein is rapid, sensitive, and specific and should be useful for understanding the ongoing evolution of carbapenem resistance in Gram-negative bacteria. As novel bla(KPC) variants continue to emerge, the MB-PCR assay can be modified in response to epidemiologic developments

Chinese immigrants have high rates of a variety of cancers and face numerous social and economic barriers to cancer treatment appointment keeping. This study is a nested cohort of 82 Chinese patients participating in the Immigrant Cancer Portal Project. Twenty-two percent reported having missed appointments for oncology follow-up, radiation therapy, and/or chemotherapy. Patients most commonly reported needing assistance with financial support to enable appointment keeping. Efforts to further address social and economic correlates in cancer care should be developed for this population

Autoregulation of cholesterol synthesis focuses on the 19 metabolic steps from lanosterol to cholesterol. Although synchronization of their rates of synthesis in all tissues was the paradigm, a known exception occurs in the ovary where a local increase in a sterol intermediate, FF-MAS (follicular fluid meiosis activating sterol), activates meiosis during oocyte maturation. Mutations in the genes that govern synchronization cause an increase in sterol intermediates that follow an alternate, oxysterol, pathway of metabolism. Experimental models in animals imply that oxysterol metabolites are determinants of the dysmorphism that occurs during fetal development in these genetic diseases. These few examples may portend a much broader role for sterol intermediates and their novel oxysterol metabolites in physiologic and pathophysiologic processes

BACKGROUND: Troponin I (TnI) is an effective marker for detecting myocardial injury, but the interpretation of levels in the setting of end-stage renal disease (ESRD) is still unclear. TnI levels have been noted to be increased in 5-18% of asymptomatic haemodialysis (HD) patients with standard assays, but newer-generation, high-sensitivity assays have not been examined. In addition, there is limited data on the variability of TnI levels in patients over time as well as the effect of HD on TnI levels. The aim of this study was to prospectively explore the incidence of TnI with a high-sensitivity assay, the variability of TnI levels over time and the effect of HD on levels. METHODS: We enrolled 51 asymptomatic HD patients and checked TnI levels using a high-sensitivity assay. Levels were drawn pre-HD monthly for three consecutive months. As per manufacturer guidelines, levels were considered normal up to 0.034 ng/mL, indeterminate elevation (IE) if between 0.035 and 0.120 ng/mL and consistent with myocardial infarction (MI) if >0.120 ng/mL. In the third month, post-HD TnI was also drawn to determine change with dialysis. RESULTS: At baseline, median TnI level was 0.025 ng/mL (range, 0-0.461 ng/mL). Baseline TnI levels were normal in 63% and elevated (>/=0.035 ng/mL) in 37%. Of those with elevations, 79% were in the IE range and 21% in the acute myocardial infarction range. Higher TnI levels at baseline were associated with a history of coronary artery disease, left ventricular hypertrophy, lower cardiac ejection fraction and higher serum phosphate levels. Average incidence of elevated TnI was 41% over the 3 months. Thirty-six patients had stable levels without a change in classification over 3 months. Twelve varied over time. Forty-five (94%) had no change in classification pre- and post-HD. CONCLUSION: Using a new-generation, high-sensitivity assay, over a third of asymptomatic ESRD patients have an elevated TnI. The significance of these low-level elevations is unclear at this time. TnI levels remain stable over a 3-month period in most patients. HD treatment does not appear to affect the TnI level

Life-history plasticity is widespread among organisms. However, an important question is whether it is adaptive. Most models for plasticity in life-history timing predict that animals, once they have reached the minimal nutritional threshold under poor conditions, will accelerate development or time to reproduction. Adaptive delays in reproduction are not common, especially in short-lived species. Examples of adaptive reproductive delays exist in mammalian populations experiencing strong interspecific (e.g., predation) and intraspecific (e.g., infanticide) competition. But are there other environmental factors that may trigger an adaptive delay in reproductive timing? We show that the short-lived flesh fly Sarcophaga crassipalpis will delay reproduction under nutrient-poor conditions, even though it has already met the minimal nutritional threshold for reproduction. We test whether this delay strategy is an adaptive response allowing the scavenger time to locate more resources by experimentally providing supplemental protein pulses (early, mid and late) throughout the reproductive delay period. Flies receiving additional protein produced more and larger eggs, demonstrating a benefit of the delay. In addition, by tracking the allocation of carbon from the pulses using stable isotopes, we show that flies receiving earlier pulses incorporated more carbon into eggs and somatic tissue than those given a later pulse. These results indicate that the reproductive delay in S. crassipalpis is consistent with adaptive post-threshold plasticity, a nutritionally linked reproductive strategy that has not been reported previously in an invertebrate species.

Staphylococcus aureus is an important pathogen that continues to be a significant global health threat because of the prevalence of methicillin-resistant S. aureus strains (MRSA). The pathogenesis of this organism is partly attributed to the production of a large repertoire of cytotoxins that target and kill innate immune cells, which provide the first line of defence against S. aureus infection. Here we demonstrate that leukocidin A/B (LukAB) is required and sufficient for the ability of S. aureus, including MRSA, to kill human neutrophils, macrophages and dendritic cells. LukAB targets the plasma membrane of host cells resulting in cellular swelling and subsequent cell death. We found that S. aureus lacking lukAB are severely impaired in their ability to kill phagocytes during bacteria-phagocyte interaction, which in turn renders the lukAB-negative staphylococci more susceptible to killing by neutrophils. Notably, we show that lukAB is expressed in vivo within abscesses in a murine infection model and that it contributes significantly to pathogenesis of MRSA in an animal host. Collectively, these results extend our understanding of how S. aureus avoids phagocyte-mediated clearance, and underscore LukAB as an important factor that contributes to staphylococcal pathogenesis

Little Fockers [Motion Picture] -- [...] beta blockers can sometimes precipitate impotence by preventing the penis from getting all the blood it needs to create and sustain an erection

127 Hours [Motion Picture] -- How could he then cut off his own arm with a pocket knife without fainting, going crazy with the pain or bleeding to death? -- The reality When faced with certain death, primordial instincts take over, says Dr. Leon Pachter, chief of surgery at New York University Langone Medical Center. Ralston said in his accounts that he had developed a 'compartment syndrome' from the trapped limb -- a condition in which the muscles, nerves and blood vessels are crushed together in a closed space

BACKGROUND:Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men. METHODS:In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878. FINDINGS/RESULTS:During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60-0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63-0·93, p=0·008). INTERPRETATION/CONCLUSIONS:Our findings indicate that male circumcision should now be accepted as an efficacious intervention for reducing the prevalence and incidence of HPV infections in female partners. However, protection is only partial; the promotion of safe sex practices is also important. FUNDING/BACKGROUND:The Bill & Melinda Gates Foundation, National Institutes of Health, and Fogarty International Center.

The doctors preserved the skull bone for later replanting. Since surgery, they have used short-acting drugs to put Ms. Giffords in a medical coma that they lift periodically to check on her neurological responses.