Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI

Functional polymorphisms in the P2X7 receptor gene are associated with stress fracture injury

Context: Military recruits and elite athletes are susceptible to stress fracture injuries. Genetic predisposition has been postulated to have a role in their development. The P2X7 receptor (P2X7R) gene, a key regulator of bone remodelling, is a genetic candidate that may contribute to stress fracture predisposition. Objective: To evaluate the putative contribution of P2X7R to stress fracture injury in two separate cohorts, military personnel and elite athletes. Methods: In 210 Israeli Defence Forces (IDF) military conscripts, stress fracture injury was diagnosed (n=43) based on symptoms and a positive bone scan. In a separate cohort of 518 elite athletes, self-reported medical imaging scan-certified stress fracture injuries were recorded (n=125). Non-stress fracture controls were identified from these cohorts who had a normal bone scan or no history or symptoms of stress fracture injury. Study participants were genotyped for functional SNPs within the P2X7R gene using proprietary fluorescence-based competitive allele-specific PCR assay. Pearson Chi-square (χ2) tests, corrected for multiple comparisons, were used to assess associations in genotype frequencies. Results: The variant allele of P2X7R SNP rs3751143 (Glu496Ala- loss of function) was associated with stress fracture injury, while the variant allele of rs1718119 (Ala348Thr- gain of function) was associated with a reduced occurrence of stress fracture injury in military conscripts (P<0.05). The association of the variant allele of rs3751143 with stress fractures was replicated in elite athletes (P<0.05), whereas the variant allele of rs1718119 was also associated with reduced multiple stress fracture cases in elite athletes (P<0.05). Conclusions: The association between independent P2X7R polymorphisms with stress fracture prevalence supports the role of a genetic predisposition in the development of stress fracture injury

Stabilization of angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid

Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system (RAAS), is a promising candidate as a treatment for cancer that reflects its antiproliferative and anti-angiogenic properties. However, the peptide’s therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer

The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder

Genome-wide association studies in bipolar disorder (BD)1 have implicated a single-nucleotide polymorphism (rs1006737, G right arrow A) in the CACNA1C gene, which encodes for the alpha 1c (CAV1.2) subunit of the voltage-gated, L-type calcium channel. Neuroimaging studies of healthy individuals report that this risk allele modulates brain function within limbic (amygdala, anterior cingulate gyrus) and hippocampal regions during tasks of reward processing2, 3 and episodic memory. Moreover, animal studies suggest that the CaV1.2 L-type calcium channels influence emotional behaviour through enhanced neurotransmission via the lateral amygdala pathway. On the basis of this evidence, we tested the hypotheses that the CACNA1C rs1006737 risk allele will modulate neural responses within predefined prefrontal and subcortical regions of interest during emotional face processing and that this effect would be amplified in BD patients

Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

Chandra High Energy Transmission Gratings Spectra of V3890 Sgr

The recurrent nova (RN) V3890 Sgr was observed during the 7th day after the onset of its most recent outburst, with the Chandra ACIS-S camera and High Energy Transmission Gratings (HETG). A rich emission line spectrum was detected, due to transitions of Fe-L and K-shell ions ranging from neon to iron. The measured absorbed flux is $\approx 10^{-10}$ erg cm$^{-2}$ s$^{-1}$ in the 1.4-15 Angstrom range (0.77-8.86 keV). The line profiles are asymmetric, blue-shifted and skewed towards the blue side, as if the ejecta moving towards us are less absorbed than the receding ones. The full width at half maximum of most emission lines is 1000-1200 km s$^{-1}$, with some extended blue wings. The spectrum is thermal and consistent with a plasma in collisional ionization equilibrium with column density 1.3 $\times 10^{22}$ cm$^{-2}$ and at least two components at temperatures of about 1 keV and 4 keV, possibly a forward and a reverse shock, or regions with differently mixed ejecta and red giant wind. The spectrum is remarkably similar to the symbiotic RNe V745 Sco and RS Oph, but we cannot distinguish whether the shocks occurred at a distance of few AU from the red giant, or near the giant's photosphere, in a high density medium containing only a small mass. The ratios of the flux in lines of aluminum, magnesium and neon relative to the flux in lines of silicon and iron probably indicate a carbon-oxygen white dwarf (CO WD)

Dental skill mix: a cross-sectional analysis of delegation practices between dental and dental hygiene-therapy students involved in team training in the South of England

BACKGROUND: Research suggests that health professionals who have trained together have a better understanding of one another’s scope of practice and are thus equipped for teamwork during their professional careers. Dental hygiene-therapists (DHTs) are mid-level providers that can deliver routine care working alongside dentists. This study examines patterns of delegation (selected tasks and patients) by dental students to DHT students training together in an integrated team. METHODS: A retrospective sample of patient data (n = 2,063) was extracted from a patient management system showing the treatment activities of two student cohorts (dental and DHT) involved in team training in a primary care setting in the South of England over two academic years. The data extracted included key procedures delegated by dental students to DHT students coded by skill-mix of operator (e.g., fissure sealants, restorations, paediatric extractions) and patient demography. χ(2) tests were conducted to investigate the relationship between delegation and patient age group, gender, smoking status, payment-exemption status, and social deprivation. RESULTS: A total of 2,063 patients managed during this period received treatments that could be undertaken by either student type; in total, they received 14,996 treatment procedures. The treatments most commonly delegated were fissure sealants (90%) and restorations (51%); whilst the least delegated were paediatric extractions (2%). Over half of these patients (55%) had at least one instance of delegation from a dental to a DHT student. Associations were found between delegation and patient age group and smoking status (P <0.001). Children under 18 years old had a higher level of delegation (86%) compared with adults of working age (50%) and patients aged 65 years and over (56%). A higher proportion of smokers had been delegated compared with non-smokers (45% cf. 26%; P <0.001). CONCLUSIONS: The findings suggest that delegation of care to DHT students training as a team with dental students, involved significantly greater experience in treating children and adult smokers, and providing preventive rather than invasive care in this integrated educational and primary care setting. The implications for their contribution to dentistry and the dental team are discussed, along with recommendations for primary care data recording

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Alternative scenarios: harnessing mid-level providers and evidence-based practice in primary dental care in England through operational research

Background: In primary care dentistry, strategies to reconfigure the traditional boundaries of various dental professional groups by task sharing and role substitution have been encouraged in order to meet changing oral health needs. Aim: The aim of this research was to investigate the potential for skill mix use in primary dental care in England based on the undergraduate training experience in a primary care team training centre for dentists and mid-level dental providers. Methods: An operational research model and four alternative scenarios to test the potential for skill mix use in primary care in England were developed, informed by the model of care at a primary dental care training centre in the south of England, professional policy including scope of practice and contemporary evidence-based preventative practice. The model was developed in Excel and drew on published national timings and salary costs. The scenarios included the following: “No Skill Mix”, “Minimal Direct Access”, “More Prevention” and “Maximum Delegation”. The scenario outputs comprised clinical time, workforce numbers and salary costs required for state-funded primary dental care in England. Results: The operational research model suggested that 73% of clinical time in England’s state-funded primary dental care in 2011/12 was spent on tasks that may be delegated to dental care professionals (DCPs), and 45- to 54-year-old patients received the most clinical time overall. Using estimated National Health Service (NHS) clinical working patterns, the model suggested alternative NHS workforce numbers and salary costs to meet the dental demand based on each developed scenario. For scenario 1:“No Skill Mix”, the dentist-only scenario, 81% of the dentists currently registered in England would be required to participate. In scenario 2: “Minimal Direct Access”, where 70% of examinations were delegated and the primary care training centre delegation patterns for other treatments were practised, 40% of registered dentists and eight times the number of dental therapists currently registered would be required; this would save 38% of current salary costs cf. “No Skill Mix”. Scenario 3: “More Prevention”, that is, the current model with no direct access and increasing fluoride varnish from 13.1% to 50% and maintaining the same model of delegation as scenario 2 for other care, would require 57% of registered dentists and 4.7 times the number of dental therapists. It would achieve a 1% salary cost saving cf. “No Skill Mix”. Scenario 4 “Maximum Delegation” where all care within dental therapists’ jurisdiction is delegated at 100%, together with 50% of restorations and radiographs, suggested that only 30% of registered dentists would be required and 10 times the number of dental therapists registered; this scenario would achieve a 52% salary cost saving cf. “No Skill Mix”. Conclusion: Alternative scenarios based on wider expressed treatment need in national primary dental care in England, changing regulations on the scope of practice and increased evidence-based preventive practice suggest that the majority of care in primary dental practice may be delegated to dental therapists, and there is potential time and salary cost saving if the majority of diagnostic tasks and prevention are delegated. However, this would require an increase in trained DCPs, including role enhancement, as part of rebalancing the dental workforce