The interfascicular matrix enables fascicle sliding and recovery in tendon, and behaves more elastically in energy storing tendons

While the predominant function of all tendons is to transfer force from muscle to bone and position the limbs, some tendons additionally function as energy stores, reducing the cost of locomotion. Energy storing tendons experience extremely high strains and need to be able to recoil efficiently for maximum energy storage and return. In the equine forelimb, the energy storing superficial digital flexor tendon (SDFT) has much higher failure strains than the positional common digital extensor tendon (CDET). However, we have previously shown that this is not due to differences in the properties of the SDFT and CDET fascicles (the largest tendon subunits). Instead, there is a greater capacity for interfascicular sliding in the SDFT which facilitates the greater extensions in this particular tendon (Thorpe et al., 2012). In the current study, we exposed fascicles and interfascicular matrix (IFM) from the SDFT and CDET to cyclic loading followed by a test to failure. The results show that IFM mechanical behaviour is not a result of irreversible deformation, but the IFM is able to withstand cyclic loading, and is more elastic in the SDFT than in the CDET. We also assessed the effect of ageing on IFM properties, demonstrating that the IFM is less able to resist repetitive loading as it ages, becoming stiffer with increasing age in the SDFT. These results provide further indications that the IFM is important for efficient function in energy storing tendons, and age-related alterations to the IFM may compromise function and predispose older tendons to injury

A cost-effectiveness analysis of a hydration response technology dressing in the treatment of venous leg ulcers in the UK

Introduction: Venous leg ulceration causes significant pain and suffering for patients, additionally it places considerable financial and service burden on the National Health Service (NHS). A large proportion of venous leg ulceration do not heal within the standard time frames of 16 – 24 weeks, resulting in static wounds which commonly have issues with increasing exudate production. Static wounds can have significant negative impact on the patients quality of life, the wound bed and periwound skin, increased risk of infection all of which results in delayed wound healing and increased health service costs. As the NHS continues to face times of austerity, services need to find solutions to be able to reduce cost and release nursing time whilst maintaining standards of care. Cutimed® Sorbion® Sachet S is a treatment option for the management of patients with a venous leg ulceration. The objective of this study was to provide an update of the health economic analysis of Cutimed® Sorbion® Sachet S in comparison to relevant comparators in the UK with current cost data. Methods: Cutimed® Sorbion® Sachet S was compared against Zetuvit Plus, DryMax extra, KerraMax Care and Eclypse from a cost effectiveness perspective. Clinical data were derived from literature and expert opinion. Cost input was utilized based on publicly available data and literature. The average patient in the model is assumed to be 65 years with a diagnosed venous leg ulcer. It is assumed that patients in the different treatment arms have the same background mortality, hence the endpoint mortality is not included in the model. The analysis is based on a deterministic Markov model derived from Harding et al. with weekly cycles. The following assumptions are made: First, all patients start in a static health state with a non-healed but non-progressing venous leg ulcer. It is assumed in the model that patients can transition to a deteriorating health state where a wound is improving or the wound could progress. Additionally, venous leg ulcers could be healed from a progressed wound (i.e. improved wound), they could develop into a severe wound with complications (infections) to be treated in hospitals. The time frame for the analysis was fixed for one year and no re-occurence after healing was assumed to happen. Results: The cost-effectiveness analysis demonstrates health economic dominance of Cutimed® Sorbion® Sachet S being more effective and cost-saving against all analysed comparators. When using literature-based input values the incrementally higher healing rates for Cutimed® Sorbion® Sachet S are 11.04 months (versus Zetuvit Plus), 29.04 months (versus DryMax extra), 1.68 months (versus KerraMax Care) and 11.04 months (versus Eclypse). Cost savings per patient were 37.60£ (versus Zetuvit Plus), 171.68£ (versus DryMax extra), 3.13£ (versus KerraMax Care) and 43.63£ (versus Eclypse). Clinical benefits and cost savings are increasing when real life practice assumptions based on expert opinion are included. Conclusions: Based on the underlying health economic model, Cutimed® Sorbion® Sachet S is more effective and less costly than other comparative products in venous leg ulcers in the UK

The Role of Zinc in the Modulation of Neuronal Proliferation and Apoptosis

Although a requirement of zinc (Zn) for normal brain development is well documented, the extent to which Zn can modulate neuronal proliferation and apoptosis is not clear. Thus, we investigated the role of Zn in the regulation of these two critical events. A low Zn availability leads to decreased cell viability in human neuroblastoma IMR-32 cells and primary cultures of rat cortical neurons. This occurs in part as a consequence of decreased cell proliferation and increased apoptotic cell death. In IMR-32 cells, Zn deficiency led to the inhibition of cell proliferation through the arrest of the cell cycle at the G0/G1 phase. Zn deficiency induced apoptosis in both proliferating and quiescent neuronal cells via the intrinsic apoptotic pathway. Reductions in cellular Zn triggered a translocation of the pro-apoptotic protein Bad to the mitochondria, cytochrome c release, and caspase-3 activation. Apoptosis is the resultant of the inhibition of the prosurvival extracellular-signal-regulated kinase, the inhibition of nuclear factor-kappa B, and associated decreased expression of antiapoptotic proteins, and to a direct activation of caspase-3. A deficit of Zn during critical developmental periods can have persistent effects on brain function secondary to a deregulation of neuronal proliferation and apoptosis

Water dynamics in Shewanella oneidensis at ambient and high pressure using quasi-elastic neutron scattering

Quasielastic neutron scattering (QENS) is an ideal technique for studying water transport and relaxation dynamics at pico- to nanosecond timescales and at length scales relevant to cellular dimensions. Studies of high pressure dynamic effects in live organisms are needed to understand Earth’s deep biosphere and biotechnology applications. Here we applied QENS to study water transport in Shewanella oneidensis at ambient (0.1 MPa) and high (200 MPa) pressure using H/D isotopic contrast experiments for normal and perdeuterated bacteria and buffer solutions to distinguish intracellular and transmembrane processes. The results indicate that intracellular water dynamics are comparable with bulk diffusion rates in aqueous fluids at ambient conditions but a significant reduction occurs in high pressure mobility. We interpret this as due to enhanced interactions with macromolecules in the nanoconfined environment. Overall diffusion rates across the cell envelope also occur at similar rates but unexpected narrowing of the QENS signal appears between momentum transfer values Q = 0.7–1.1 Å−1 corresponding to real space dimensions of 6–9 Å. The relaxation time increase can be explained by correlated dynamics of molecules passing through Aquaporin water transport complexes located within the inner or outer membrane structures

Evaluation of the function and quality of life of patients submitted to girdlestone's resection arthroplasty

OBJECTIVES: To evaluate function and quality of life of patients submitted to Girdlestone's arthroplasty, and to compare outcomes between unilateral Girdlestone's group with the group with contralateral total hip prosthesis. METHODS: Cross-sectional study where 9 patients were evaluated with unilateral Girdlestone's and 3 with Girdlestone's in one hip and contralateral total hip prosthesis. The evaluation consisted in filling in a generic questionnaire on quality of life SF-36 and a specific questionnaire for hip function Harris Hip Score (HHS). The comparison between groups was made by using the Student's t-test and the Fisher's test. RESULTS: The patients of the unilateral Girdlestone's group presented a higher number of SF-36 domains classified as high, although 77.8% of these showed poor results on the HHS. All patients had a leg-length discrepancy and positive Trendelenburg's test, which led to limping gait in 11 of 12 patients evaluated. Of these, only 6 underwent physiotherapy after surgery. CONCLUSION: Girdlestone's postoperative quality of life and function in a Brazilian population still requires further studies, because these outcomes are indicative of study variables' behavior and cannot be regarded as definite.OBJETIVOS: Avaliar a função e a qualidade de vida dos pacientes pós-artroplastia de Girdlestone e comparar os resultados entre os grupos Girdlestone unilateral e o grupo com prótese total de quadril contralateral. MÉTODOS: estudo transversal no qual foram avaliados 9 pacientes com Girdlestone unilateral e 3 com Girdlestone em um quadril e prótese total no quadril contralateral. A avaliação constitui-se em aplicar o questionário genérico de qualidade de vida SF-36 e um questionário funcional específico para o quadril, Harris Hip Score (HHS). A comparação dos grupos foi realizada usando-se o teste t- Student e o teste de Fisher. RESULTADOS: Os pacientes do grupo Girdlestone unilateral apresentaram maior quantidade de domínios do SF-36 classificados como elevados, embora 77,8% destes tenham obtido resultados ruins no HHS. Todos os pacientes apresentaram o teste de Trendelenburg positivo e discrepância de membros, o que levou à marcha claudicante em 11 dos 12 pacientes avaliados. Destes, apenas 6 submeteram-se a fisioterapia pós-operatória. CONCLUSÃO: A qualidade de vida e a função pós-operatória de Girdlestone, na população brasileira, ainda necessita ser mais pesquisada, pois estes resultados são indicações do comportamento das variáveis de estudo e não podem ser consideradas encerradas.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Ortopedia e TraumatologiaUNIFESP-EPM DOTUNIFESP, EPM, Depto. de Ortopedia e TraumatologiaUNIFESP, EPM DOTSciEL

Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa.

Circulating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. In 15 patient plasma samples collected at the time of diagnosis as part of the Ghana Breast Health Study and unselected for tumor grade and subtype, ctDNA was detected in a majority of patients based on whole- genome sequencing at high (30×) and low (0.1×) depths. Breast cancer driver copy number alterations were observed in the majority of patients

Anhydrobiosis and Freezing-Tolerance:Adaptations That Facilitate the Establishment of Panagrolaimus Nematodes in Polar Habitats

<div><p>Anhydrobiotic animals can survive the loss of both free and bound water from their cells. While in this state they are also resistant to freezing. This physiology adapts anhydrobiotes to harsh environments and it aids their dispersal. <i>Panagrolaimus davidi</i>, a bacterial feeding anhydrobiotic nematode isolated from Ross Island Antarctica, can survive intracellular ice formation when fully hydrated. A capacity to survive freezing while fully hydrated has also been observed in some other Antarctic nematodes. We experimentally determined the anhydrobiotic and freezing-tolerance phenotypes of 24 <i>Panagrolaimus</i> strains from tropical, temperate, continental and polar habitats and we analysed their phylogenetic relationships. We found that several other <i>Panagrolaimus</i> isolates can also survive freezing when fully hydrated and that tissue extracts from these freezing-tolerant nematodes can inhibit the growth of ice crystals. We show that <i>P. davidi</i> belongs to a clade of anhydrobiotic and freezing-tolerant panagrolaimids containing strains from temperate and continental regions and that <i>P. superbus</i>, an early colonizer at Surtsey island, Iceland after its volcanic formation, is closely related to a species from Pennsylvania, USA. Ancestral state reconstructions show that anhydrobiosis evolved deep in the phylogeny of <i>Panagrolaimus</i>. The early-diverging <i>Panagrolaimus</i> lineages are strongly anhydrobiotic but weakly freezing-tolerant, suggesting that freezing tolerance is most likely a derived trait. The common ancestors of the <i>davidi</i> and the <i>superbus</i> clades were anhydrobiotic and also possessed robust freezing tolerance, along with a capacity to inhibit the growth and recrystallization of ice crystals. Unlike other endemic Antarctic nematodes, the life history traits of <i>P. davidi</i> do not show evidence of an evolved response to polar conditions. Thus we suggest that the colonization of Antarctica by <i>P. davidi</i> and of Surtsey by <i>P. superbus</i> may be examples of recent “ecological fitting” of freezing-tolerant anhydrobiotic propagules to the respective abiotic conditions in Ross Island and Surtsey.</p></div

Demographic variation in incidence of adult glioma by subtype, United States, 1992-2007

<p>Abstract</p> <p>Background</p> <p>We hypothesized that race/ethnic group, sex, age, and/or calendar period variation in adult glioma incidence differs between the two broad subtypes of glioblastoma (GBM) and non-GBM. Primary GBM, which constitute 90-95% of GBM, differ from non-GBM with respect to a number of molecular characteristics, providing a molecular rationale for these two broad glioma subtypes.</p> <p>Methods</p> <p>We utilized data from the Surveillance, Epidemiology, and End Results Program for 1992-2007, ages 30-69 years. We compared 15,088 GBM cases with 9,252 non-GBM cases. We used Poisson regression to calculate adjusted rate ratios and 95% confidence intervals.</p> <p>Results</p> <p>The GBM incidence rate increased proportionally with the 4^thpower of age, whereas the non-GBM rate increased proportionally with the square root of age. For each subtype, compared to non-Hispanic Whites, the incidence rate among Blacks, Asians/Pacific Islanders, and American Indians/Alaskan Natives was substantially lower (one-fourth to one-half for GBM; about two-fifths for non-GBM). Secondary to this primary effect, race/ethnic group variation in incidence was significantly less for non-GBM than for GBM. For each subtype, the incidence rate was higher for males than for females, with the male/female rate ratio being significantly higher for GBM (1.6) than for non-GBM (1.4). We observed significant calendar period trends of increasing incidence for GBM and decreasing incidence for non-GBM. For the two subtypes combined, we observed a 3% decrease in incidence between 1992-1995 and 2004-2007.</p> <p>Conclusions</p> <p>The substantial difference in age effect between GBM and non-GBM suggests a fundamental difference in the genesis of primary GBM (the driver of GBM incidence) versus non-GBM. However, the commonalities between GBM and non-GBM with respect to race/ethnic group and sex variation, more notable than the somewhat subtle, albeit statistically significant, differences, suggest that within the context of a fundamental difference, some aspects of the complex process of gliomagenesis are shared by these subtypes as well. The increasing calendar period trend of GBM incidence coupled with the decreasing trend of non-GBM incidence may at least partly be due to a secular trend in diagnostic fashion, as opposed to real changes in incidence of these subtypes.</p