Ubiquitin regulates dissociation of DNA repair factors from chromatin.

This is the final version of the article. It first appeared from Impact Journals via http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=441

Initiatives to integrate primary and acute health care, including ambulatory care services

Most people, at some time in their lives, will require health care services from multiple health care providers, whether it is for short-term unexpected ill health, long-term chronic conditions or co-morbidities that cross disciplines (eg. substance-related conditions and mental health). Integration of health services is particularly important for patients with chronic and complex conditions as they must frequently negotiate a path through different health care sectors, including primary, acute and ambulatory care services, as well as the public and private health jurisdictions. Standardised pathways for the more common chronic conditions may be needed to enable seamless transitions and avoid negative outcomes that may result from delays, duplications and errors in a system that operates as multiple independent organisations

Health literacy and primary health care

People with low levels of health literacy report poorer health status and experience poorer health outcomes compared to those with good health literacy. Poor health literacy is most prevalent in socio-economically disadvantaged populations, which are often in greater need of health care to manage complex conditions. In recognition of its potential positive impact on health outcomes, improving the health literacy of populations is being incorporated into policy. This RESEARCH ROUNDup reports on some recent developments in health literacy research and the role of primary health care in enhancing health literacy to improve health outcomes

Regionally-based needs assessment in Australian primary health care.

Needs assessments in primary health care provide information to plan and change services, with the ultimate goal of improving the health of a population. It is the first step in health care services planning, and involves identifying and analysing a region’s health problems and potential target group. For the purposes of this report, need was defined as “the population’s ability to benefit” as this lends itself most usefully to health services planning. This report also reflects on International and Australian models that may inform approaches to needs assessments in Australia

Characterization of a Temperature-Sensitive Vertebrate Clathrin Heavy Chain Mutant as a Tool to Study Clathrin-Dependent Events In Vivo

Clathrin and clathrin-dependent events are evolutionary conserved although it is believed that there are differences in the requirement for clathrin in yeast and higher vertebrates. Clathrin is a long-lived protein and thus, with clathrin knockdowns only long-term consequences of clathrin depletion can be studied. Here, we characterize the first vertebrate temperature-sensitive clathrin heavy chain mutant as a tool to investigate responses to rapid clathrin inactivation in higher eukaryotes. Although we created this mutant using a clathrin cryo-electron microscopy model and a yeast temperature-sensitive mutant as a guide, the resulting temperature-sensitive clathrin showed an altered phenotype compared to the corresponding yeast temperature-sensitive clathrin. First, it seemed to form stable triskelions at the non-permissive temperature although endocytosis was impaired under these conditions. Secondly, as a likely consequence of the stable triskelions at the non-permissive temperature, clathrin also localized correctly to its target membranes. Thirdly, we did not observe missorting of the lysosomal enzyme beta-glucuronidase which could indicate that the temperature-sensitive clathrin is still operating at the non-permissive temperature at the Golgi or, that, like in yeast, more than one TGN trafficking pathway exists. Fourthly, in contrast to yeast, actin does not appear to actively compensate in general endocytosis. Thus, there seem to be differences between vertebrates and yeast which can be studied in further detail with this newly created tool

Multicenter assessment of quantitative sensory testing (QST) for the detection of neuropathic-like pain responses using the topical capsaicin model

Background: The use of quantitative sensory testing (QST) in multicenter studies has been quite limited, due in part to lack of standardized procedures among centers. Aim: The aim of this study was to assess the application of the capsaicin pain model as a surrogate experimental human model of neuropathic pain in different centers and verify the variation in reports of QST measures across centers. Methods: A multicenter study conducted by the Quebec Pain Research Network in six laboratories allowed the evaluation of nine QST parameters in 60 healthy subjects treated with topical capsaicin to model unilateral pain and allodynia. The same measurements (without capsaicin) were taken in 20 patients with chronic neuropathic pain recruited from an independent pain clinic. Results: Results revealed that six parameters detected a significant difference between the capsaicin-treated and the control skin areas: (1) cold detection threshold (CDT) and (2) cold pain threshold (CPT) are lower on the capsaicin-treated side, indicating a decreased in cold sensitivity; (3) heat pain threshold (HPT) was lower on the capsaicin-treated side in healthy subjects, suggesting an increased heat pain sensitivity; (4) dynamic mechanical allodynia (DMA); (5) mechanical pain after two stimulations (MPS2); and (6) mechanical pain summation after ten stimulations (MPS10), are increased on the capsaicin-treated side, suggesting an increased in mechanical pain (P < 0.002). CDT, CPT and HPT showed comparable effects across all six centers, with CPT and HPT demonstrating the best sensitivity. Data from the patients showed significant difference between affected and unaffected body side but only with CDT. Conclusion: These results provide further support for the application of QST in multicenter studies examining normal and pathological pain responses

Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice

Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) has been linked to an increased risk of developing cardiovascular disease in addition to the well-documented physicochemical-dependent adverse lung effects. A proposed mechanism is through a strong and sustained pulmonary secretion of acute phase proteins to the blood. We identified physicochemical determinants of MWCNT-induced systemic acute phase response by analyzing effects of pulmonary exposure to 14 commercial, well-characterized MWCNTs in female C57BL/6J mice pulmonary exposed to 0, 6, 18 or 54 μg MWCNT/mouse. Plasma levels of acute phase response proteins serum amyloid A1/2 (SAA1/2) and SAA3 were determined on day 1, 28 or 92. Expression levels of hepatic Saa1 and pulmonary Saa3 mRNA levels were assessed to determine the origin of the acute phase response proteins. Pulmonary Saa3 mRNA expression levels were greater and lasted longer than hepatic Saa1 mRNA expression. Plasma SAA1/2 and SAA3 protein levels were related to time and physicochemical properties using adjusted, multiple regression analyses. SAA3 and SAA1/2 plasma protein levels were increased after exposure to almost all of the MWCNTs on day 1, whereas limited changes were observed on day 28 and 92. SAA1/2 and SAA3 protein levels did not correlate and only SAA3 protein levels correlated with neutrophil influx. The multiple regression analyses revealed a protective effect of MWCNT length on SAA1/2 protein level on day 1, such that a longer length resulted in lowered SAA1/2 plasma levels. Increased SAA3 protein levels were positively related to dose and content of Mn, Mg and Co on day 1, whereas oxidation and diameter of the MWCNTs were protective on day 28 and 92, respectively. The results of this study reveal very differently controlled pulmonary and hepatic acute phase responses after MWCNT exposure. As the responses were influenced by the physicochemical properties of the MWCNTs, this study provides the first step towards designing MWCNT that induce less SAA