Versican splice variant messenger RNA expression in normal human Achilles tendon and tendinopathies

Versican is the principal large proteoglycan expressed in mid-tendon, but its role in tendon pathology is unknown. Our objective was to define the expression of versican isoform splice variant messenger ribonucleic acid (mRNA) in normal Achilles tendons, in chronic painful tendinopathy and in ruptured tendons. Total RNA isolated from frozen tendon samples (normal n = 14; chronic painful tendinopathy n = 10; ruptured n = 8) was assayed by relative quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for total versican, versican variants V0, V1, V2, V3 and type I collagen a1 mRNA, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Differences between sample groups were tested by Wilcoxon statistics. Painful and ruptured tendons showed a significant decrease (median 2-fold) in the expression of versican mRNA, in contrast to an increased expression (median 8-fold) of type I collagen a1 mRNA in painful tendons. Versican splice variants V0 and V1 mRNA were readily detected in normal samples, V3 levels were substantially lower, and V2 levels were more variable. Each of V1, V2 and V3 mRNA showed significant decreases in expression in painful and ruptured tendons, but V0 was not significantly changed. Changes in versican expression relative to that of collagen, and alterations in the balance of versican splice variants, may contribute to changes in matrix structure and function in tendinopathies

Designing clinical trials in trauma surgery: overcoming research barriers.

The surgical community is plagued with a reputation for both failing to engage and to deliver on clinical research. This is in part due to the absence of a strong research culture, however it is also due to a multitude of barriers encountered in clinical research; particularly those involving surgical interventions. 'Trauma' amplifies these barriers, owing to the unplanned nature of care, unpredictable work patterns, the emergent nature of treatment and complexities in the consent process. This review discusses the barriers to clinical research in surgery, with a particular emphasis on trauma. It considers how barriers may be overcome, with the aim to facilitate future successful clinical research

Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand

Background: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine.Objective: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life.Methods: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, I-123-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method.Results: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with (p<0.01) and controls (p<0.001) in the caudate nucleus and the anterior and posterior Putamen.Conclusion: FP-CIT SPET provides a means of distinguishing DLB from AD during life

Difficulty in performing activities of daily living and the need for help in older adults: evidence on social distancing models from the ELSI-COVID-19 initiative

To analyze whether the older adults with difficulty or need of help to perform basic or instrumentals activities of daily living are more socially distanced in times of COVID-19. A total of 4,035 older adults participated in the telephone interviews from the second wave of the Brazilian Longitudinal Study of Aging (ELSI-Brazil). Difficulty, need and receiving help were classified into: (1) independents; (2) had difficulty without need for care; (3) had difficulty, needed and have received care from someone within their household; (4) had difficulty, needed and have received care from someone outside their household; and (5) had difficulty and needed care but did not receive it. Social distancing was categorized as follows: did not leave their houses in the last 7 days, left their houses for essential activities and went out for non-essential activities. Multinomial regression model adjusted for age, sex, schooling and great geographical region was performed. Older adults who had difficulty, needed and have received help from within their homes (odds ratio - OR = 2.34 95%CI: 1.25-4.39) or from outside their homes (OR = 3.94; 95%CI: 2.24-6.92) were more socially distanced. Age increased the odds of not going out (OR = 1.06; 95%CI: 1.03-1.09) while be men reduced it (OR = 0.48; 95%CI: 0.33-0.70). Living in the South of Brazil has increased the odds of the respondents going out for essential activities (OR = 1.77; 95%CI: 1.01-3.10). Older adults who had difficulty, needed and have received help from within or outside their homes did not leave their homes in the last 7 days. Even with social distancing, these older adults can not have their exposure to COVID-19 reduced, weakening the theory of selective social distancing

Complex network view of evolving manifolds

We study complex networks formed by triangulations and higher-dimensional simplicial complexes representing closed evolving manifolds. In particular, for triangulations, the set of possible transformations of these networks is restricted by the condition that at each step, all the faces must be triangles. Stochastic application of these operations leads to random networks with different architectures. We perform extensive numerical simulations and explore the geometries of growing and equilibrium complex networks generated by these transformations and their local structural properties. This characterization includes the Hausdorff and spectral dimensions of the resulting networks, their degree distributions, and various structural correlations. Our results reveal a rich zoo of architectures and geometries of these networks, some of which appear to be small worlds while others are finite-dimensional with Hausdorff dimension equal or higher than the original dimensionality of their simplices. The range of spectral dimensions of the evolving triangulations turns out to be from about 1.4 to infinity. Our models include simplicial complexes representing manifolds with evolving topologies, for example, an h-holed torus with a progressively growing number of holes. This evolving graph demonstrates features of a small-world network and has a particularly heavy-tailed degree distribution.Comment: 14 pages, 15 figure

Hospital case volume and outcomes for proximal femoral fractures in the USA: an observational study

Objective: To explore whether older adults with isolated hip fractures benefit from treatment in high-volume hospitals. Design: Population-based observational study. Setting: All acute hospitals in California, USA. Participants: All individuals aged >65 that underwent an operation for an isolated hip fracture in California between 2007 and 2011. Patients transferred between hospitals were excluded. Primary and secondary outcomes: Quality indicators (time to surgery) and patient outcomes (length of stay, in-hospital mortality, unplanned 30-day re-admission, and selected complications). Results: 91,401 individuals satisfied the inclusion criteria. Time to operation and length of stay were significantly prolonged in low volume hospitals, by 1.96 (95% CI 1.20-2.73) and 0.70 (0.38-1.03) days respectively. However, there were no differences in clinical outcomes, including in-hospital mortality, 30-day re-admission, and rates of pneumonia, pressure ulcers, and venous thromboembolism. Conclusion: These data suggest that there is no patient safety imperative to limit hip fracture care to high-volume hospitals

The Legionella pneumophila Dot/Icm type IV secretion system and its effectors

To prevail in the interaction with eukaryotic hosts, many bacterial pathogens use protein secretion systems to release virulence factors at the host–pathogen interface and/or deliver them directly into host cells. An outstanding example of the complexity and sophistication of secretion systems and the diversity of their protein substrates, effectors, is the Defective in organelle trafficking/Intracellular multiplication (Dot/Icm) Type IVB secretion system (T4BSS) of Legionella pneumophila and related species. Legionella species are facultative intracellular pathogens of environmental protozoa and opportunistic human respiratory pathogens. The Dot/Icm T4BSS translocates an exceptionally large number of effectors, more than 300 per L. pneumophila strain, and is essential for evasion of phagolysosomal degradation and exploitation of protozoa and human macrophages as replicative niches. Recent technological advancements in the imaging of large protein complexes have provided new insight into the architecture of the T4BSS and allowed us to propose models for the transport mechanism. At the same time, significant progress has been made in assigning functions to about a third of L. pneumophila effectors, discovering unprecedented new enzymatic activities and concepts of host subversion. In this review, we describe the current knowledge of the workings of the Dot/Icm T4BSS machinery and provide an overview of the activities and functions of the to-date characterized effectors in the interaction of L. pneumophila with host cells