Identification of Legionella pneumophila genes required for growth within and killing of human macrophages.

Legionella pneumophila was mutagenized with Tn903dIIlacZ, and a collection of mutants was screened for defects in macrophage killing (Mak-). Of 4,564 independently derived mutants, 55 (1.2%) showed a reduced or complete lack in the ability to kill HL-60-derived human macrophages. Forty-nine of the Mak- mutants could be assigned to one of 16 DNA hybridization groups. Only one group (9 of the 10 members) could be complemented for macrophage killing by a DNA fragment containing icm and dot, two recently described L. pneumophila loci that are required for macrophage killing. Phenotypic analysis showed that none of the mutants were any more sensitive than the wild type to human serum, oxidants, iron chelators, or lipophilic reagents nor did they require additional nutrients for growth. The only obvious difference between the Mak-mutants and wild-type L. pneumophila was that almost all of the Mak- mutants were resistant to NaCl. The effects of LiCl paralleled the effects of NaCl but were less pronounced. Resistance to salt and the inability to kill human macrophages are linked since both phenotypes appeared when Tn903dIIlacZ mutations from two Mak- strains were transferred to wild-type backgrounds. However, salt sensitivity is not a requisite for killing macrophages since a group of Mak- mutants containing a plasmid that restored macrophage killing remained resistant to NaCl. Mak- mutants from groups I through IX associated with HL-60 cells similarly to wild-type L. pneumophila. However, like the intracellular-multiplication-defective (icm) mutant 25D, the Mak- mutants were unable to multiply within macrophages. Thus, the ability of L. pneumophila to kill macrophages seems to be determined by many genetic loci, almost all of which are associated with sensitivity to NaCl.     

Endoscopic ultrasound‐guided fine‐needle aspiration diagnosis of large cell neuroendocrine carcinoma of the gallbladder and common bile duct: Report of a case

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) allows a reliable and accurate diagnosis of neoplasms of the gallbladder and bile ducts. We report the cytopathologic findings of a case of large cell neuroendocrine carcinoma (LCNEC) of the gallbladder and extrahepatic bile ducts in a 67‐year‐old woman who presented with progressive abdominal pain and jaundice. EUS‐FNA of the mass involving the common bile duct and of a porta hepatis lymph node showed abundant cellularity with tumor cells arranged singly and occasionally in tight and loose clusters and rosette‐like structures in a background showing extensive necrotic debris. The tumor cells were predominantly plasmacytoid, showed a moderate amount of focally vacuolated cytoplasm and large round to oval hyperchromatic nuclei with prominent nucleoli, numerous mitoses, and apoptotic bodies. The differential diagnosis included poorly differentiated adenocarcinoma, lymphoma, melanoma, and poorly differentiated neuroendocrine carcinoma (NEC), large cell type. The tumor cells were strongly and diffusely positive for cytokeratin AE1/AE3, CD56, synaptophysin, and chromogranin and showed a very high proliferative fraction on Ki67 staining, supporting the diagnosis of a high‐grade NEC. Due to the large size of the neoplastic cells, moderate amounts of cytoplasm and prominent nucleoli, a diagnosis of LCNEC was made on the EUS‐FNA sample. Despite the prompt institution of chemotherapy, the patient died shortly thereafter and the diagnosis was confirmed at autopsy. This is to our knowledge the first case of LCNEC of the gallbladder and bile ducts diagnosed by EUS‐FNA. Diagn. Cytopathol. 2013;41:1091–1095. © 2012 Wiley Periodicals, Inc.     

The Performance of Graphene-Enhanced THz Grating: Impact of the Gold Layer Imperfectness

We report the performance of a graphene-enhanced THz grating fabricated by depositing a gold layer on the femtosecond micromachined SiO₂ substrate. The morphology of the gold plated patterned substrate was studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM), while the quality of the chemical vapor deposition (CVD) graphene was evaluated by Raman spectroscopy. The electromagnetic (EM) response of the metasurface comprising the graphene sheet and the gold plated substrate was studied by THz time domain spectroscopy in the 100 GHz–1 THz frequency range. We employed the finite elements method (FEM) to model the metasurface EM response by adjusting the ac conductivity of the gold layer covering the patterned SiO₂ substrate to reproduce the measured transmission/reflection spectra. The results of the numerical simulation reveal the impact of the imperfectness of the gold layer on the performance of the THz metasurface. The experimental results are well described in terms of the Drude–Smith model of metal conductivity that takes into account the anisotropic scattering of the carriers in thin metal films.     

Deconstructing male violence against women: the men stopping violence community-accountability model

Men Stopping Violence (MSV), a 24-year-old metro Atlanta-based organization that works to end male violence against women, uses an ecological, community-based accountability model as the foundation of its analysis of the problem of male violence against women and of its work with individuals and in communities. The MSV community-accountability model of male violence against women offers a view of the cultural and historical mechanisms that support violence against women. The model, and the strategies and programs that have grown out of it, demonstrate the potential for disrupting traditions of abuse and dominance at the individual, familial, local, national, and global levels.     

Selecting an Appropriate Medication for Treating Neuropathic Pain in Patients with Diabetes: A Study Using the U.K. and Germany Mediplus Databases

Objective:   To evaluate the appropriateness of prescribing select neuropathic pain medications to diabetes patients based on the potential for drug–drug interactions with medications diabetes patients were prescribed continuously for ≥ 3 months (chronic use).
Methods:   Medical records of patients with a diagnosis of diabetes or use of antidiabetic medications between January 1, 2002 and September 30, 2005 in the U.K. and Germany Mediplus databases were obtained.
Patients:   Medication use profiles were evaluated between April 2004 and September 2005. The metabolic pathways associated with medications that were prescribed chronically to at least 10% of study patients were compared with the metabolic pathways of neuropathic pain medications to identify potential drug–drug interactions.
Results:   A total of 40,448 patients in the U.K. (63.6 ± 16.6 years, 51% male) and 31,930 patients in Germany (68.9 ± 12.7 years, 46% male) were identified. Frequently prescribed medications in the U.K. included aspirin (33.7%), metformin (32.7%), simvastatin (25.5%), atorvastatin (19.4%), atenolol (18.1%), and in Germany hydrochlorothiazide (35.8%), aspirin (25.2%), metformin (21.6%), metoprolol (20.3%), and simvastatin (18.3%). Several neuropathic pain medications have potential for drug–drug interactions with medications prescribed to diabetes patients. Examples include (neuropathic pain medications vs. diabetes medications): duloxetine, paroxetine, and methadone (CYP2D6 inhibitors) and oxycodone HCL, hydrocodone (CYP2D6 substrates) vs. metoprolol and bisoprolol (CYP2D6 substrates); and carbamazepine (CYP3A4 inducer) vs. simvastatin, and atorvastatin (CYP3A4 substrates).
Conclusions/Interpretation:   Our findings underscore the need for medical vigilance when selecting medications for treating neuropathic pain in diabetes patients. ▪     

Losing a loved one to homicide: Prevalence and mental health correlates in a national sample of young adults

The present study examined the prevalence, demographic distribution, and mental health correlates of losing a loved one to homicide. A national sample of 1,753 young adults completed structured telephone interviews measuring violence exposure, mental health diagnoses, and loss of a family member or close friend to a drunk driving accident (vehicular homicide) or murder (criminal homicide). The prevalence of homicide survivorship was 15%. African Americans were more highly represented among criminal homicide survivors. Logistic regression analyses found that homicide survivors were at risk for past year posttraumatic stress disorder (OR = 1.88), major depressive episode (OR = 1.64), and drug abuse/dependence (OR = 1.77). These findings highlight the significant mental health needs of homicide survivors.