The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary

Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under‐described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild‐type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Completed suicide at age 50 and over

The authors present data abstracted from medical examiners' investigative reports of 246 completed suicides of persons over the age of 50 years classified into four age groups. The sample population conformed to epidemiologic studies with regard to sex distribution. With increasing age, more suicide victims were widowed, and significantly fewer were single, separated, or divorced. Violent methods of suicide were more prevalent and alcohol use and psychiatric histories less common with aging. Physical illness and loss became the most common definable precipitants to suicide, whereas job, financial, and family relationship problems became less frequent with increasing age. The indications for future research and intervention in primary care settings are discussed.     

【特刊综述】雄激素对骨骼肌的作用：对乏力的发展和治疗的意义

雄激素对骨骼肌合成有明显影响,随着年龄增大,雄激素的下降常伴随肌量和肌力的下降。这种肌量和肌功能的下降,被称为少肌症或肌体老化,是老年人体质弱化（男性化减退）进展的关键事项。也是导致快速机能衰退及其不良后果的关键。雄激素水平下降对老年男性体质弱化（男性化减退）的潜在影响和对躯体功能的促进治疗作用无疑已经引起了相当的关注。本综述概述了近期关于肌肉老化、少肌症、老年体质弱化的概念、定义,并评估了关于雄激素和老年体质弱化的研究进展。近期源于观测性和介入性研究的证据强烈支持雄激素对老年男性肌量的作用,但雄激素对肌力和特有的躯体功能的效用并不明确。研究显示,雄激素治疗在老年男性中通常有良好的耐受性,而近期的研究则关注于雄激素的高剂量治疗和对于心血管风险较高人群的治疗。雄激素受体调节剂（SARMs）的初期试验研究显示传统雄激素治疗对于老年患者在肌量和肌功能方面有相同的效用。将来的重要研究方向包括利用这类雄激素治疗并结合适用于不同老年患者群体促进躯体功能的运动训练,同时将更多地关注近期关于激素水平、身体成分及躯体功能间关系的观测性（回顾性）研究。     

Nitric oxide interactions with cobalamins: biochemical and functional consequences

Nitric oxide (NO) is a paramagnetic gas that has been implicated in a wide range of biologic functions. The common pathway to evoke the functional response frequently involves the formation of an iron- nitrosyl complex in a target (heme) protein. In this study, we report on the interactions between NO and cobalt-containing vitamin B12 derivatives. Absorption spectroscopy showed that of the four Co(III) derivatives (cyanocobalamin [CN-Cbl], aquocobalamin [H2O-Cbl], adenosylcobalamin [Ado-Cbl], and methylcobalamin [MeCbl]), only the H2O- Cbl combined with NO. In addition, electron paramagnetic resonance spectroscopy of H2O-Cbl preparations showed the presence of a small amount of Cob-(II)alamin that was capable of combining with NO. The Co(III)-NO complex was very stable, but could transfer its NO moiety to hemoglobin (Hb). The transfer was accompanied by a reduction of the Co(III) to Co(II), indicating that NO+ (nitrosonium) was the leaving group. In accordance with this, the NO did not combine with the Hb Fe(II)-heme, but most likely with the Hb cysteine-thiolate. Similarly, the Co(III)-NO complex was capable of transferring its NO to glutathione. Ado-Cbl and Me-Cbl were susceptible to photolysis, but CN- Cbl and H2O-Cbl were not. The homolytic cleavage of the Co(III)-Ado or Co(III)-Me bond resulted in the reduction of the metal. When photolysis was performed in the presence of NO, formation of NO-Co(II) was observed. Co(II)-nitrosyl oxidized slowly to form Co(III)-nitrosyl. The capability of aquocobalamin to combine with NO had functional consequences. We found that nitrosylcobalamin had diminished ability to serve as a cofactor for the enzyme methionine synthase, and that aquocobalamin could quench NO-mediated inhibition of cell proliferation. Our in vitro studies therefore suggest that interactions between NO and cobalamins may have important consequences in vivo.     

Early Hemoconcentration Predicts Increased Mortality Only among Transferred Patients with Acute Pancreatitis

Background/Aims: The prognostic utility of hemoconcentration in acute pancreatitis (AP) remains controversial. Methods: We examined the relationship between early hemoconcentration and in-hospital mortality in an observational cohort study. Data was collected from 177 US hospitals from January 2004 to September 2005. Early hemoconcentration was defined as hemoglobin ≥14.6 mg/dl (hematocrit ～44%)atany point during the first 24 h of initial hospitalization. For transferred cases, we linked clinical data from the first hospitalization to outcomes from the second hospitalization. We then examined the impact of hospital transfer status on the prognostic utility of hemoconcentration. Results: We identified 388 (2.2%) cases as interhospital transfers. Of these, we successfully linked 198 (51.0%) to their initial hospitalization. Early hemoconcentration was associated with increased mortality among transferred cases (OR 7.4, 95% CI 1.6, 35.4). However, no such relationship existed among non-transferred cases (OR 0.9,95% CI 0.7,1.2). Differences in outcome between transferred vs. nontransferred cases were not explained by extent of comorbid illness or initial disease severity (either APACHE II or organ failure). Conclusions: Early hemoconcentration predicted increased risk of mortality only among transferred cases despite similar levels of initial disease severity. These findings may help explain discordant results from prior studies of hemoconcentration in AP.     

Culture, risk factors and suicide in rural China: a psychological autopsy case control study

OBJECTIVE: Previous research on sociocultural factors for Chinese suicide have been basically limited to single case studies or qualitative research with ethnographic methodology. The current study examines the major risk factors and some cultural uniqueness related to Chinese rural suicide using a quantitative design. METHOD: This is a case control study with 66 completed suicides and 66 living controls obtained from psychological autopsy interviews in rural China. RESULTS: Both bivariate analyses and the multiple regression model have found that the Chinese rural suicide patterns are basically similar to those in most other cultures in the world: strong predictors of rural Chinese suicide are the psychopathological, psychological, and physical health variables, followed by social support and negative and stressful life events. Other significant correlates include lower education, poverty, religion, and family disputes. CONCLUSION: Culture has an important impact on suicide patterns in a society.