Sub-10-micrometer toughening and crack tip toughness of dental enamel

In previous studies, enamel showed indications to occlude small cracks in-vivo and exhibited R-curve behaviors for bigger cracks ex-vivo. This study quantifies the crack tip's toughness (K(I0),K(III0)), the crack's closure stress and the cohesive zone size at the crack tip of enamel and investigates the toughening mechanisms near the crack tip down to the length scale of a single enamel crystallite. The crack-opening-displacement (COD) profile of cracks induced by Vickers indents on mature bovine enamel was studied using atomic force microscopy (AFM). The mode I crack tip toughness K(I0) of cracks along enamel rod boundaries and across enamel rods exhibit a similar range of values: K(I0,Ir)=0.5-1.6MPa?m(0.5) (based on Irwin's 'near-field' solution) and K(I0,cz)=0.8-1.5MPa?m(0.5) (based on the cohesive zone solution of the Dugdale-Muskhelishvili (DM) crack model). The mode III crack tip toughness K(III0,Ir) was computed as 0.02-0.15MPa?m(0.5). The crack-closure stress at the crack tip was computed as 163-770?MPa with a cohesive zone length and width 1.6-10.1μm and 24-44?nm utilizing the cohesive zone solution. Toughening elements were observed under AFM and SEM: crack bridging due to protein ligament and hydroxyapatite fibres (micro- and nanometer scale) as well as microcracks were identified.     

Antisense oligonucleotides delivered to the mouse CNS ameliorate symptoms of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene that result in a deficiency of SMN protein. One approach to treat SMA is to use antisense oligonucleotides (ASOs) to redirect the splicing of a paralogous gene, SMN2, to boost production of functional SMN. Injection of a 2'-O-2-methoxyethyl-modified ASO (ASO-10-27) into the cerebral lateral ventricles of mice with a severe form of SMA resulted in splice-mediated increases in SMN protein and in the number of motor neurons in the spinal cord, which led to improvements in muscle physiology, motor function and survival. Intrathecal infusion of ASO-10-27 into cynomolgus monkeys delivered putative therapeutic levels of the oligonucleotide to all regions of the spinal cord. These data demonstrate that central nervous system-directed ASO therapy is efficacious and that intrathecal infusion may represent a practical route for delivering this therapeutic in the clinic.     

A quick guide to positioning the transbuccal set

Exact positioning of the transbuccal set can be tricky, especially under aggravating circumstances as present scarring or high body mass index. It may result in multiple skin incisions. This article presents a simple and fast guidance technique that can help in the exact positioning of skin incision and transbuccal set.     

A Conceptual Definition of Vocational Rehabilitation Based on the ICF: Building a Shared Global Model

Background The International Classification of Functioning, Disability and Health (ICF) is a conceptual framework and classification system by the World Health Organization (WHO) to understand functioning. The objective of this discussion paper is to offer a conceptual definition for vocational rehabilitation (VR) based on the ICF. Method We presented the ICF as a model for application in VR and the rationale for the integration of the ICF. We also briefly reviewed other work disability models. Results Five essential elements of foci were found towards a conceptual definition of VR: an engagement or re-engagement to work, along a work continuum, involved health conditions or events leading to work disability, patient-centered and evidence-based, and is multi-professional or multidisciplinary. Conclusions VR refers to a multi-professional approach that is provided to individuals of working age with health-related impairments, limitations, or restrictions with work functioning and whose primary aim is to optimize work participation. We propose that the ICF and VR interface be explored further using empirical and qualitative works and encouraging stakeholders?? participation.     

Fatal case of brucellosis misdiagnosed in early stages of Brucella suis infection in a 46-year-old patient with Marfan syndrome

We report a fatal case of Brucella suis endocarditis initially misdiagnosed by automated identification systems as Ochrobactrum anthropi infection in a patient with a history of Marfan syndrome and recreational feral swine hunting. This report emphasizes the need to consider brucellosis as a part of the differential diagnosis of acute febrile illness, particularly in patients with known risk of exposure.     

Sensitivity and specificity of finding of multinucleate trophoblastic giant cells in decidua in placentas from high-risk pregnancies

This is a retrospective analysis of sensitivity and specificity of clustered placental basal plate multinucleate trophoblastic giant cells for various clinical conditions and placental lesions associated with fetal and placental hypoxia. Selected clinical and placental parameters of 375 consecutive cases of placentas with clusters of multinucleate trophoblastic giant cell (at least 3 cells with at least 3 nuclei) in the decidua (study group) were compared with all remaining 2674 placentas concurrently studied (control group) in 20-week-or-more high-risk pregnancies. Multinucleate trophoblastic giant cell was found in 12.3% of placentas. The study group had statistically significantly more cases of preeclampsia, abnormal Dopplers, induction of labor, and cesarean sections, with its placentas lighter and with more common other hypoxic lesions than in the control-group placentas. The multinucleate trophoblastic giant cell prevalence negatively correlated with gestational age (R = -0.56), peaking at the turn of the second and the third trimesters of pregnancy and declining afterward, and most strongly correlated with the excessive amount of extravillous trophoblasts in the chorionic disc (R = +0.33). The sensitivity of multinucleate trophoblastic giant cells was, on average, 3 times lower than the specificity, the latter averaging greater than 90%. In conclusion, finding of multinucleate trophoblastic giant cells is not exclusively limited to uteroplacental malperfusion of preeclampsia but is also seen in other types of high-risk pregnancy and in association with other placental hypoxic lesions and patterns. Multinucleate trophoblastic giant cells most likely reflect a premature fusion of extravillous trophoblasts because of several factors, likely including also hypoxia. Being highly specific, finding the multinucleate trophoblastic giant cells is unlikely to give a false-positive result and therefore has high value in retrospectively explaining the perinatal morbidity and mortality.     

Examining the similarities and differences of OMERACT core sets using the ICF: first step towards an improved domain specification and development of an item pool to measure functioning and health

OBJECTIVE: To contribute to the discussion on a common approach for domain selection in the Outcomes in Rheumatology Clinical Trials (OMERACT) process. First, this article reports on the consistency in the selection and names of the domains of the current OMERACT core set, and next on the comparability of the specifications of concepts that are relevant within the domains. For this purpose, a convenience sample of 4 OMERACT core sets was used: rheumatoid arthritis (RA), psoriatic arthritis (PsA), longitudinal observational studies (LOS) in rheumatology, and ankylosing spondylitis (AS). Domains from the different core sets were compared directly. To be able to compare the specific content of the domains, the concepts contained in the questionnaires that were considered or proposed to measure the domains were identified and linked to the category of the International Classification of Functioning, Disability, and Health (ICF) that best fit that construct. Large differences in the domains, and lack of domain definitions, were noted among the 4 OMERACT core sets. When comparing the concepts in the questionnaires that represent the domains, core sets differed also in the number and type of constructs that were addressed within each of the domains. Especially for the specification of the concepts within the domains Discomfort and Disability, the ICF proved to be useful as external reference to classify the different constructs. Our exercise suggests that the OMERACT process could benefit from a standardized approach to select, define, and specify domains, and demonstrated that the ICF is useful for further classification of the more specific concepts of "what to measure" within the domains. A clear definition and classification of domains and their specification can be useful as a starting point to build a pool of items that could then be used to develop new instruments to assess functioning and health for rheumatological conditions.