Multifactorial effects of hyperglycaemia, hyperinsulinemia and inflammation on bone remodelling in type 2 diabetes mellitus.

Bones undergo continuous cycles of bone remodelling that rely on the balance between bone formation and resorption. This balance allows the bone to adapt to changes in mechanical loads and repair microdamages. However, this balance is susceptible to upset in various conditions, leading to impaired bone remodelling and abnormal bones. This is usually indicated by abnormal bone mineral density (BMD), an indicator of bone strength. Despite this, patients with type 2 diabetes mellitus (T2DM) exhibit normal to high BMD, yet still suffer from an increased risk of fractures. The activity of the bone cells is also altered as indicated by the reduced levels of bone turnover markers in T2DM observed in the circulation. The underlying mechanisms behind these skeletal outcomes in patients with T2DM remain unclear. This review summarises recent findings regarding inflammatory cytokine factors associated with T2DM to understand the mechanisms involved and considers potential therapeutic interventions.

Stability of peatland carbon to rising temperatures.

Peatlands contain one-third of soil carbon (C), mostly buried in deep, saturated anoxic zones (catotelm). The response of catotelm C to climate forcing is uncertain, because prior experiments have focused on surface warming. We show that deep peat heating of a 2 m-thick peat column results in an exponential increase in CH4 emissions. However, this response is due solely to surface processes and not degradation of catotelm peat. Incubations show that only the top 20-30 cm of peat from experimental plots have higher CH4 production rates at elevated temperatures. Radiocarbon analyses demonstrate that CH4 and CO2 are produced primarily from decomposition of surface-derived modern photosynthate, not catotelm C. There are no differences in microbial abundances, dissolved organic matter concentrations or degradative enzyme activities among treatments. These results suggest that although surface peat will respond to increasing temperature, the large reservoir of catotelm C is stable under current anoxic conditions.

Reorientation of health services: enablers and barriers faced by organisations when increasing health promotion capacity.

Issue addressed Primary healthcare settings are important providers of health promotion approaches. However, organisational challenges can affect their capacity to deliver these approaches. This review identified the common enablers and barriers health organisations faced and it aimed to explore the experiences health organisations, in particular Aboriginal organisations, had when increasing their health promotion capacity. Methods A systematic search of peer-reviewed literature was conducted. Articles published between 1990-2014 that focused on a health care-settings approach and discussed factors that facilitated or hindered an organisation's ability to increase health promotion capacity were included. Results Twenty-five articles met the inclusion criteria. Qualitative (n=18) and quantitative (n=7) study designs were included. Only one article described the experiences of an Aboriginal health organisation. Enablers included: management support, skilled staff, provision of external support to the organisation, committed staffing and financial resources, leadership and the availability of external partners to work with. Barriers included: lack of management support, lack of dedicated health promotion staff, staff lacking skills or confidence, competing priorities and a lack of time and resources allocated to health promotion activities. Conclusions While the literature highlighted the importance of health promotion work, barriers can limit the delivery of health promotion approaches within primary healthcare organisations. A gap in the literature exists about how Aboriginal health organisations face these challenges. So what? Primary healthcare organisations wanting to increase their health promotion capacity can pre-empt the common barriers and strengthen identified enablers through the shared learnings outlined in this review.

Measuring the sustainability of a community safety promotion network: working from the inside out.

Mackay Whitsunday Safe Communities (MWSC) was developed using a capacity building model that consciously attempted to design sustainability into the network. Our aim was to quantify the flow of resources used by MWSC to implement and sustain its injury control activities. Resource exchange among network members was quantified and analysed using social network analysis. In 2004, MWSC accessed an estimated 6.5 full-time staff equivalents and $0.9 million. However, these resources were largely accessed externally. The linking relationships that connected MWSC to its external support network, more than half of which were maintained by six broker network facilitators, were the critical social asset used to access resources and sustain network productivity. The sustainability of this network and arguably similar safety promotion networks is vulnerable to the changing priorities of external sponsoring agents and highly dependent on its leaders who facilitated access to the resources it required to remain productive.

The process and outcomes of a nurse-led colorectal cancer follow-up clinic.

AIM: Evidence suggests that follow-up after colorectal cancer improves survival. Colorectal cancer is so common that patient follow-up can overwhelm a service, affecting the ability to see new referrals and reassess patients seen previously who have new symptoms. In order to cope with this demand a nurse-led follow-up service was started in 2004. We aimed to review the results of a nurse-led colorectal cancer follow-up clinic. METHOD: Between 1 December 2004 and 31 January 2011, patients who underwent resection for colorectal cancer were followed up by a nurse specialist according to a protocol determined by the colorectal surgeons in the unit. All patient details were recorded prospectively in a purpose designed database. RESULTS: Nine hundred and fifty patients were followed up over 7 years. Some 368 patients were discharged from the follow-up programme, 474 patients remain actively involved in the programme and 108 patients died. Of the patients discharged from the follow-up scheme 269 (73%) were discharged to their general practitioner free of disease after 5 years. Of the 108 who patients died, 98 were as a result of colorectal cancer. Twenty patients (2.1%) were identified with local (peri-anastomotic) disease recurrence and 93 patients (9.8%) were found to have developed distant metastatic disease. Of these, 65 patients (6.8%) were referred for palliative care and 28 (2.9%) had surgery for focal metastatic disease of whom 18 were still alive at the time of this analysis. CONCLUSION: This paper shows that a nurse-led clinic for colorectal cancer follow-up can achieve satisfactory results with detection rates of recurrent or metastatic disease comparable to consultant follow-up. A nurse-led clinic provides the benefits of follow-up without overwhelming the consultant colorectal surgical clinic practice.

Bilateral obturator hernia with intestinal obstruction: repair with a cigar roll technique.

Obturator hernia is an exceedingly rare pelvic hernia that occurs primarily in multiparous, elderly thin (>70 years of age) females. Here, we report a case of bilateral obturator hernia in an elderly female with high-grade small bowel obstruction repaired with a novel "cigar roll" technique.

Two-pore domain K channel, TASK-1, in pulmonary artery smooth muscle cells.

Pulmonary vascular tone is strongly influenced by the resting membrane potential of smooth muscle cells, depolarization promoting Ca2+ influx, and contraction. The resting potential is determined largely by the activity of K+-selective ion channels, the molecular nature of which has been debated for some time. In this study, we provide strong evidence that the two-pore domain K+ channel, TASK-1, mediates a noninactivating, background K+ current (IKN), which sets the resting membrane potential in rabbit pulmonary artery smooth muscle cells (PASMCs). TASK-1 mRNA was found to be present in PASMCs, and the membranes of PASMCs contained TASK-1 protein. Both IKN and the resting potential were found to be exquisitely sensitive to extracellular pH, acidosis inhibiting the current and causing depolarization. Moreover, IKN and the resting potential were enhanced by halothane (1 mmol/L), inhibited by Zn2+ (100 to 200 micromol/L) and anandamide (10 micromol/L), but insensitive to cytoplasmic Ca2+. These properties are all diagnostic of TASK-1 channels and add to previously identified features of IKN that are shared with TASK-1, such as inhibition by hypoxia, low sensitivity to 4-aminopyridine and quinine and insensitivity to tetraethylammonium ions. It is therefore concluded that TASK-1 channels are major contributors to the resting potential in pulmonary artery smooth muscle. They are likely to play an important role in mediating pulmonary vascular responses to changes in extracellular pH, and they could be responsible for the modulatory effects of pH on hypoxic pulmonary vasoconstriction.

S K- and Mo L-edge X-ray absorption spectroscopy to determine metal-ligand charge distribution in molybdenum-sulfur compounds.

Mo L-edge and S K-edge X-ray absorption spectroscopy were applied to investigate the charge distribution between Mo and S in a series of Mo thiolate compounds, which serve as amide-sulfur H-bonding models and exhibit different redox potentials arising from polar group effects and ligand hydrogen bonds near the redox center. For all oxidized complexes, the S K-edge spectra exhibit a thiolate-based pre-edge feature centered at 2470.2 eV and the inflection point oCCurs at 2472.0 eV. No intense pre-edge feature is observed in the spectra for the reduced Mo model compounds and the energy shift of the S K-edge position depends on the S-ligand. Correlations between ligand charge density and the redox potential of the Mo-S cores are observed.

High-resolution X-ray spectroscopy of rare events: a different look at local structure and chemistry.

The combination of large-acceptance high-resolution X-ray optics with bright synchrotron sources permits quantitative analysis of rare events such as X-ray fluorescence from very dilute systems, weak fluorescence transitions or X-ray Raman scattering. Transition-metal Kbeta fluorescence contains information about spin and oxidation state; examples of the characterization of the Mn oxidation states in the oxygen-evolving complex of photosystem II and Mn-consuming spores from the marine bacillus SG- are presented. Weaker features of the Kbeta spectrum resulting from valence-level and 'interatomic' ligand to metal transitions contain detailed information on the ligand- atom type, distance and orientation. Applications of this spectral region to characterize the local structure of model compounds are presented. X-ray Raman scattering (XRS) is an extremely rare event, but also represents a unique technique to obtain bulk-sensitive low-energy (<600 eV) X-ray absorption fine structure (XAFS) spectra using hard (approximately 10 keV) X-rays. A photon is inelastically scattered, losing part of its energy to promote an electron into an unoccupied level. In many cases, the cross section is proportional to that of the corresponding absorption process yielding the same X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) features. XRS finds application for systems that defy XAFS analysis at low energies, e.g. liquids or highly concentrated complex systems, reactive compounds and samples under extreme conditions (pressure, temperature). Recent results are discussed.

Measurement of the electric form factor of the neutron through d-->(e-->,e(')n)p at Q2 = 0.5 (GeV/c)(2).

We report the first measurement using a solid polarized target of the neutron electric form factor G(n)(E) via d-->(e-->,e(')n)p. G(n)(E) was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia ( 15ND3). The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility in quasifree kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find G(n)(E) = 0.04632+/-0.00616(stat)+/-0.00341(syst) at Q2 = 0.495 (GeV/c)(2).

Absence of Mn-centered oxidation in the S(2) --> S(3) transition: implications for the mechanism of photosynthetic water oxidation.

A key question for the understanding of photosynthetic water oxidation is whether the four oxidizing equivalents necessary to oxidize water to dioxygen are accumulated on the four Mn ions of the oxygen-evolving complex (OEC), or whether some ligand-centered oxidations take place before the formation and release of dioxygen during the S(3) --> [S(4)] --> S(0) transition. Progress in instrumentation and flash sample preparation allowed us to apply Mn Kbeta X-ray emission spectroscopy (Kbeta XES) to this problem for the first time. The Kbeta XES results, in combination with Mn X-ray absorption near-edge structure (XANES) and electron paramagnetic resonance (EPR) data obtained from the same set of samples, show that the S(2) --> S(3) transition, in contrast to the S(0) --> S(1) and S(1) --> S(2) transitions, does not involve a Mn-centered oxidation. On the basis of new structural data from the S(3)-state, manganese mu-oxo bridge radical formation is proposed for the S(2) --> S(3) transition, and three possible mechanisms for the O-O bond formation are presented.

Counting the number of disulfides and thiol groups in proteins and a novel approach for determining the local pKa for cysteine groups in proteins in vivo.

X-ray Absorption Spectroscopy (XAS) is a powerful tool to investigate sulfur in biological molecules. The spectral features are sensitive to the local electronic and geometric environment of the atom; thus, they constitute a fingerprint of the different chemical forms in which the sulfur is present. This allows straightforward detection of the ratio between free thiols and disulfides. Intra- or inter-molecular disulfide bond formation between residues plays an important role in structural and conformational changes in proteins, and such changes can be investigated using sulfur XAS. Also, a thiolate-disulfide equilibrium is involved in the regulation of the redox potential in the cells by means of modulating the concentrations of the reduced (thiolate) and oxidized (disulfide) form of the tripeptide glutathione. Thus, we can monitor the redox state of a cell by means of sulfur XAS. Thiols also exhibit an acid-base equilibrium, and sulfur XAS can be used to determine the local pKa of the -SH group. Here we report examples of how sulfur XAS has been used for these applications.

HIV-1 seroprevalence in chest clinic and hospital tuberculosis patients in New York City, 1989-1991.

OBJECTIVE: To describe more fully HIV-1 and tuberculosis (TB) coinfection in TB patients attending New York City Department of Health chest clinics (1989-1991) and one inner-city hospital (1990-1991). DESIGN: An unlinked serosurvey using HIV-1-antibody testing of remnant blood specimens collected for routine medical purposes. SUBJECTS: A total of 1414 clinic and 856 hospital patients. OUTCOME MEASURES: HIV seropositivity and TB infection/disease. RESULTS: A total of 327 (23%) of the clinic patients were HIV-1-positive, with a significantly higher seroprevalence in men (29 versus 15%, P < 0.001) and in young and middle-aged adults aged 30-50 years (P < 0.001). HIV-1 prevalence by TB diagnostic class was: class 2 (purified protein derivative-positive and chest radiograph-negative), 11% (64 out of 570); class 3 (active disease), 34% (197 out of 582); class IV (old/inactive disease), 30% (39 out of 130). Of the hospital patients 487 (57%) were HIV-1-positive. HIV-1 seroprevalence was 55% for those who were identified or believed to be HIV-1-negative on admission as indicated on the medical chart. HIV-1 seroprevalence in the clinic population decreased initially, but later increased, although not to study onset levels. CONCLUSIONS: There is considerable overlap between the TB and HIV epidemics in New York City; a part of the increasing TB incidence may be independent of HIV coinfection. The control of TB will necessitate prompt diagnosis of TB and HIV-1, appropriate TB treatment and/or chemoprophylaxis, and a greater commitment to tackle the social conditions associated with the spread of the disease.

Collagen content in human ulnar nerve.

A quantitative analysis of ulnar nerve collagen in the arm and forearm was undertaken in nine subjects. While endoneurial collagen was found to be significantly increased within the cubital tunnel, extrafascicular collagen did not increase at the elbow except in two nerves showing fusiform enlargements. Renaut bodies increased in frequency at sites of high endoneurial collagen content. Morphological determinations of cross-sectional area along the ulnar nerve did not correlate with quantitative collagen data.