Beryllium and lung cancer: a weight of evidence evaluation of the toxicological and epidemiological literature.

The potential carcinogenicity of beryllium has been a topic of study since the mid-1940s. Since then, numerous scientific and regulatory bodies have assigned beryllium to various categories with respect to its carcinogenicity. Past epidemiologic and animal studies, however, have been marked with notable methodological shortcomings. Because it has been about 16 yr since IARC evaluated beryllium and approximately 50 relevant papers on the topic have been published since that time, we conducted a weight-of-evidence analysis of the historical as well as recent animal and human literature. We also assessed whether recently published studies improved upon methodological shortcomings or shed light upon uncertainties in prior studies. Thirty-three animal studies, principally designed to evaluate the cancer hazard or related mechanisms, and seventeen epidemiologic studies were considered in this assessment. Based on this analysis, the evidence for carcinogenicity of beryllium is not as clear as suggested by previous evaluations, because of the inadequacy of the available smoking history information, the lack of well-characterized historical occupational exposures and shortcomings in the animal studies. We concluded that the increase in potential risk of lung cancer was observed among those exposed to very high levels of beryllium and that beryllium's carcinogenic potential in humans at exposure levels that exist in modern industrial settings should be considered either inadequate or marginally suggestive.

Molecular characterization of a nosocomial outbreak of influenza B virus in an acute care hospital setting.

AIM: To describe a hospital outbreak of influenza B virus (InfB) infection during season 2015/2016 by combining clinical and epidemiological data with molecular methods. METHODS: Twenty patients diagnosed with InfB from a hospital outbreak over a four-week-period were included. Nasopharyngeal samples (NPS) positive for InfB by multiplex real-time polymerase chain reaction were sent for lineage typing and whole genome sequencing (WGS). Medical records were reviewed retrospectively for data regarding patient characteristics, localization, exposure and outcome, and assembled into a timeline. In order to find possible connections to the hospital outbreak, all patients with a positive NPS for influenza from the region over an extended time period were also reviewed. FINDINGS: All 20 cases of InfB were of subtype B/Yamagata, and 17 of 20 patients could be linked to each other by either shared room or shared ward. WGS was successful or partially successful for 15 of the 17 viral isolates, and corroborated the epidemiological link supporting a close relationship. In the main affected ward, 19 of 75 inpatients were infected with InfB during the outbreak period, resulting in an attack rate of 25%. One probable case of influenza-related death was identified. CONCLUSION: InfB may spread within an acute care hospital, and advanced molecular methods may facilitate assessment of the source and extent of the outbreak. A multi-faceted approach, including rapid diagnosis, early recognition of outbreak situations, simple rules for patient management and the use of regular infection control measures, may prevent nosocomial transmission of influenza virus.

Effective control measures limited measles outbreak after extensive nosocomial exposures in January-February 2008 in Gothenburg, Sweden.

In January-February 2008, one imported case of measles initiated a series of exposures with around 380 nosocomial secondary contacts. Susceptible individuals were traced early and control measures were initiated that managed to limit the consequences considerably. Only four secondary cases were identified by the end of March. This minor outbreak illustrates the importance and efficiency of early control measures as well as the fact that the risk of measles outbreaks still exists in a country that has high measles, mumps, rubella vaccination coverage among children.

Antibiotic susceptibility of periurethral anaerobic microflora in healthy girls.

The in vitro susceptibility of sixty-four isolates of periurethral anaerobic bacteria to nine commonly used antibiotics was analyzed. Using a quantitative sampling method, the three predominant anaerobic strains were isolated from each periurethral sample of twenty-one healthy prepubertal girls. The majority of strains showed high sensitivity to ampicillin and phenoxymethylpenicillin, whereas trimethoprim and trimethoprim--sulfamethoxazole showed no or only slight inhibition of growth of most strains. Intermediate sensitivity was found to erythromycin, cefuroxime, pivmecillinam, norfloxacin and nitrofurantoin. Our data suggest that several antibiotics used in paediatric praxis might influence the indigenous periurethral anaerobic microflora. Hypothetically, this may be a factor of importance in the pathogenesis of ascending urinary tract infections.

Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria.

Variegate porphyria (VP) is an autosomal-dominant disorder that is caused by inheritance of a partial deficiency of the enzyme protoporphyrinogen oxidase (EC 1.3.3.4). It is characterized by cutaneous photosensitivity and/or various neurological manifestations. Protoporphyrinogen oxidase catalyses the penultimate step of haem biosynthesis, and mutations in the PPOX gene have been coupled to VP. In the present study, sequencing analysis revealed 10 different mutations in the PPOX gene in 14 out of 17 apparently unrelated Swedish VP families. Six of the identified mutations, 3G > A (exon 2), 454C > T (exon 5), 472G > C (exon 6), 614C > T (exon 6), 988G > C (exon 10) and IVS12 + 2T > G (intron 12), are single nucleotide substitutions, while 604delC (exon 6), 916-17delCT (exon 9) and 1330-31delCT (exon 13) are small deletions, and IVS12 + 2-3insT (intron 12) is a small insertion. Only one of these 10 mutations has been reported previously. Three of the mutations were each identified in two or more families, while the remaining mutations were specific for an individual family. In addition to the 10 mutations, one previously unreported single nucleotide polymorphism was identified. Mutation analysis of family members revealed two adults and four children who were silent carriers of the VP trait. Genetic analysis can now be added to the conventional biochemical analyses and used in investigation of putative carriers of a VP trait in these families.

Single dose treatment of cystitis in children.

The efficacy of single dose treatment with trimethoprim compared to a 5-day course with the same drug was investigated in 100 children, 3-12 years, with isolated episodes of symptomatic non-febrile urinary tract infection. Cure, defined as sterile urine during the first week after treatment, was achieved in 74% (37/50) in the single dose group compared to 86% (43/50) in the 5-day treatment group. The difference was not statistically significant (chi 2 = 2.25, p = 0.134 two-tailed). The cure rates in relation to P-fimbriation of the infecting E. coli strains were similar in the two groups. During the 6 month follow-up, six children in each treatment group had one or more reinfections. Extended studies are needed to conclude if single dose and conventional treatment courses are equally effective.

An analysis of the determinants of HMO reenrollment behavior: implications for theory and policy.

Understanding the evaluative criteria used to select a health plan is central to effective marketing of an HMO. The determinant criteria that guide the reenrollment decision are shown to differ from those that drive initial enrollment. The authors' findings suggest several operational and strategic policy implications for HMO management.

Multiple factors including subgenomic RNAs and reduced viral protein expression are associated with a persistent infection by porcine rubulavirus (LPMV).

The synthesis of virus specific RNA and the expression of viral proteins in PK-15 cells persistently infected with the porcine rubulavirus LPMV have been studied at two different cell-passages following establishment of persistency (passages 25 and 65). Protein analysis of persistently infected cells and the virus particles released from these failed to demonstrate the presence of the polymerase (L) protein. A decrease in the amount of the phospho- (P) protein was also noted. The genome and mRNAs, both mono- and bicistronic, could readily be identified in the persistently infected cells with the exception of the L mRNA. By analysis of transcription gradients generated using the NIH Image analysis software, as well as analysis of the editing frequency, it was concluded that the changes in viral protein levels in persistently infected cells could be associated with a reduction in the amount of L mRNA and a shift in editing of the P gene. In addition, several large subgenomic RNAs of both the internally deleted and copy-back type were found in the persistently infected cells. The relevance of these findings to the persistent state is discussed.

Porcine rubulavirus LPMV RNA persists in the central nervous system of pigs after recovery from acute infection.

In order to study persistence of the porcine rubulavirus LPMV, we examined tissue samples collected from pigs 53 days after experimental infection. These pigs survived the initial infection and could clinically be considered to have recovered from the infection. Two of the pigs used in this study were chemically immunosuppressed during the last 4 days before necropsy. No infectious virus or viral antigen could be detected in any tissue using standard methods for virus isolation and detection. However, the presence of viral genomic RNA and mRNA could be demonstrated in the mid brain of the convalescent pig using an optimised RT-nested PCR. Mid brain, forebrain and lung were all shown to contain LPMV RNA in the immunosuppressed convalescent pigs. In addition we examined the P-gene editing in the recovered pigs and conclude that the viral genome is transcriptionally active in these pigs. The relevance of the persistence of LPMV for maintenance and spread within and/or between pig populations is discussed.