Norovirus gastroenteritis general outbreak associated with raw shellfish consumption in South Italy

BACKGROUND: Despite Noroviruses (NV, previously "Norwalk-like viruses") being a leading cause of acute gastroenteritis outbreaks, the impact of NV infection is at present unknown and little information is available about strains circulating in Italy. In April 2002 an outbreak of gastroenteritis occurred in the province of Bari (South-east Italy), involving several households. METHODS: A retrospective cohort study was performed in order to assess risk factors associated with illness. All households where a case occurred were included in the study. Faecal specimens were collected from ill individuals. NV-specific RT-PCR was performed. Eleven samples of mussels were collected from fish-markets involved in the outbreak. A nested PCR was used for mussel samples. RESULTS: One hundred and three cases, detected by means of active surveillance, met the case definition. Raw shellfish eating was the principal risk factor for the disease, as indicated by the analytic issues (Risk Ratio: 1.50; IC 95%: 1.18 – 1.89; p < 0.001). NVs were found by means of RT-PCR of all the stool specimens from the 24 patients tested. Eleven samples of shellfish from local markets were tested for the presence or NVs; six were positive by nested PCR and genotypes were related to that found in patients' stools. CONCLUSION: This is the first community outbreak caused by NVs related to sea-food consumption described in Italy. The study confirms that the present standards for human faecal contamination do not seem to be a reliable indicator of viral contaminants in mussels

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

An ethnographic investigation of maternity healthcare experience of immigrants in rural and urban Alberta, Canada

Background: Canada is among the top immigrant-receiving nations in the world. Immigrant populations may face structural and individual barriers in the access to and navigation of healthcare services in a new country. The aims of the study were to (1) generate new understanding of the processes that perpetuate immigrant disadvantages in maternity healthcare, and (2) devise potential interventions that might improve maternity experiences and outcomes for immigrant women in Canada. Methods: The study utilized a qualitative research approach that focused on ethnographic research design and data analysis contextualized within theories of organizational behaviour and critical realism. Data were collected over 2.5 years using focus groups and in-depth semistructured interviews with immigrant women (n = 34), healthcare providers (n = 29), and social service providers (n = 23) in a Canadian province. Purposive samples of each subgroup were generated, and recruitment and data collection – including interpretation and verification of translations – were facilitated through the hiring of community researchers and collaborations with key informants. Results: The findings indicate that (a) communication difficulties, (b) lack of information, (c) lack of social support (isolation), (d) cultural beliefs, e) inadequate healthcare services, and (f) cost of medicine/services represent potential barriers to the access to and navigation of maternity services by immigrant women in Canada. Having successfully accessed and navigated services, immigrant women often face additional challenges that influence their level of satisfaction and quality of care, such as lack of understanding of the informed consent process, lack of regard by professionals for confidential patient information, short consultation times, short hospital stays, perceived discrimination/stereotyping, and culture shock. Conclusions: Although health service organizations and policies strive for universality and equality in service provision, personal and organizational barriers can limit care access, adequacy, and acceptability for immigrant women. A holistic healthcare approach must include health informational packages available in different languages/media. Health care professionals who care for diverse populations must be provided with training in cultural competence, and monitoring and evaluation programs to ameliorate personal and systemic discrimination

Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB–IIA of cervical cancer

The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from 109 patients with cervical cancer, FIGO-stage IB–IIA, treated with preoperative brachytherapy followed by radical surgery were analysed by immunohistochemistry. In addition, correlation studies between early pathological tumour response to radiation and expression of Ku86, Ku70, Mdm-2, p53 and p21 in primary tumours were also performed. We found that tumour-transformed tissue shows positive immunostaining of DNA-PKcs, Ku86 and Ku70, while non-neoplastic squamous epithelium and tumour-free cervix glands show negative immunoreactivity. Expression of DNA-PKcs positively correlated with both Ku86 and Ku70, and a statistically significant correlation between the Ku subunits was also found. After RT, 85 patients demonstrated pathologic complete remission (pCR), whereas 24 patients had residual tumour in the surgical specimen (non-pCR). The main finding of our study is that there was no correlation between the outcome of RT and the expression of DNA-PK subunits. Positive p53 tumours were significantly more common among non-pCR cases than in patients with pCR (P=0.031). Expression of p21 and Mdm-2 did not correlate with the outcome of RT

Clinicopathological Significance and Prognostic Value of DNA Methyltransferase 1, 3a, and 3b Expressions in Sporadic Epithelial Ovarian Cancer

Altered DNA methylation of tumor suppressor gene promoters plays a role in human carcinogenesis and DNA methyltransferases (DNMTs) are responsible for it. This study aimed to determine aberrant expression of DNMT1, DNMT3a, and DNMT3b in benign and malignant ovarian tumor tissues for their association with clinicopathological significance and prognostic value. A total of 142 ovarian cancers and 44 benign ovarian tumors were recruited for immunohistochemical analysis of their expression. The data showed that expression of DNMT1, DNMT3a, and DNMT3b was observed in 76 (53.5%), 92 (64.8%) and 79 (55.6%) of 142 cases of ovarian cancer tissues, respectively. Of the serious tumors, DNMT3a protein expression was significantly higher than that in benign tumor samples (P = 0.001); DNMT3b was marginally significant down regulated in ovarian cancers compared to that of the benign tumors (P = 0.054); DNMT1 expression has no statistical difference between ovarian cancers and benign tumor tissues (P = 0.837). Of the mucious tumors, the expression of DNMT3a, DNMT3b, and DNMT1 was not different between malignant and benign tumors. Moreover, DNMT1 expression was associated with DNMT3b expression (P = 0.020, r = 0.195). DNMT1 expression was associated with age of the patients, menopause status, and tumor localization, while DNMT3a expression was associated with histological types and serum CA125 levels and DNMT3b expression was associated with lymph node metastasis. In addition, patients with DNMT1 or DNMT3b expression had a trend of better survival than those with negative expression. Co-expression of DNMT1 and DNMT3b was significantly associated with better overall survival (P = 0.014). The data from this study provided the first evidence for differential expression of DNMTs proteins in ovarian cancer tissues and their associations with clinicopathological and survival data in sporadic ovarian cancer patients

Systematic quantification of gene interactions by phenotypic array analysis

A phenotypic array method, developed for quantifying cell growth, was applied to the haploid and homozygous diploid yeast deletion strain sets. A growth index was developed to screen for non-additive interacting effects between gene deletion and induced perturbations. From a genome screen for hydroxyurea (HU) chemical-genetic interactions, 298 haploid deletion strains were selected for further analysis. The strength of interactions was quantified using a wide range of HU concentrations affecting reference strain growth. The selectivity of interaction was determined by comparison with drugs targeting other cellular processes. Bio-modules were defined as gene clusters with shared strength and selectivity of interaction profiles. The functions and connectivity of modules involved in processes such as DNA repair, protein secretion and metabolic control were inferred from their respective gene composition. The work provides an example of, and a general experimental framework for, quantitative analysis of gene interaction networks that buffer cell growth

Neural protection by naturopathic compounds—an example of tetramethylpyrazine from retina to brain

Given the advantages of being stable in the ambient environment, being permeable to the blood–brain and/or blood–eye barriers and being convenient for administration, naturopathic compounds have growingly become promising therapeutic candidates for neural protection. Extracted from one of the most common Chinese herbal medicines, tetramethylpyrazine (TMP), also designated as ligustrazine, has been suggested to be neuroprotective in the central nervous system as well as the peripheral nerve network. Although the detailed molecular mechanisms of its efficacy for neural protection are understood limitedly, accumulating evidence suggests that antioxidative stress, antagonism for calcium, and suppression of pro-inflammatory factors contribute significantly to its neuroprotection. In animal studies, systemic administration of TMP (subcutaneous injection, 50 mg/kg) significantly blocked neuronal degeneration in hippocampus as well as the other vulnerable regions in brains of Sprague–Dawley rats following kainate-induced prolonged seizures. Results from us and others also demonstrated potent neuroprotective efficacy of TMP for retinal cells and robust benefits for brain in Alzheimer’s disease or other brain injury. These results suggest a promising prospect for TMP to be used as a treatment of specific neurodegenerative diseases. Given the assessment of the distribution, metabolism, excretion, and toxicity information that is already available on most neuroprotective naturopathic compounds such as TMP, it would not take much preclinical data to justify bringing such therapeutic compounds to clinical trials in humans

Identification and manipulation of tumor associated macrophages in human cancers

Evading immune destruction and tumor promoting inflammation are important hallmarks in the development of cancer. Macrophages are present in most human tumors and are often associated with bad prognosis. Tumor associated macrophages come in many functional flavors ranging from what is known as classically activated macrophages (M1) associated with acute inflammation and T-cell immunity to immune suppressive macrophages (M2) associated with the promotion of tumor growth. The role of these functionally different myeloid cells is extensively studied in mice tumor models but dissimilarities in markers and receptors make the direct translation to human cancer difficult. This review focuses on recent reports discriminating the type of infiltrating macrophages in human tumors and the environmental cues present that steer their differentiation. Finally, immunotherapeutic approaches to interfere in this process are discussed

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition