Effect of alignment perturbations in a trans-tibial prosthesis user : a pilot study

A recurring complication voiced by trans-tibial prosthetic limb users is ‘poor socket fit’ with painful residuum-socket interfaces, a consequence of excess pressure. This is attributable to both poor socket fit and poor socket alignment, however, their interaction has not been quantified. Through evaluation of kinetic data this study aimed to articulate an interaction uniting socket design, alignment and interface pressures (IPs). Results will help refine future studies, which will help determine if sockets can be designed, fitted and aligned to maximise mobility whilst minimising injurious forces. IPs were recorded throughout ambulation in one user with ‘optimal (reference) alignment’ followed by five malalignments in a patellar tendon-bearing (PTB) and a hydrocast socket. Marked differences in pressure distribution were discovered when equating the PTB against the hydrocast socket and when comparing IPs from reference to offset alignment. PTB sockets were established more sensitive to alignment perturbations than hydrocast sockets. A complex interaction was found, with the most prominent finding demonstrating the requisite for attainment of optimal alignment: a translational alignment error of 10mm can increase maximum peak pressures by 227 percent (x̄=17.5%). Refinements for future trials have been established, as has the necessity for future research regarding socket design, alignment and IPs

Mapping the Spatio-temporal Distribution of Key Vegetation Cover Properties in Lowland River Reaches, Using Digital Photography

The presence of vegetation in stream ecosystems is highly dynamic in both space and time. A digital photography technique is developed to map aquatic vegetation cover at species level, which has a very-high spatial and a flexible temporal resolution. A digital single-lens-reflex (DSLR) camera mounted on a handheld telescopic pole is used. The low-altitude (5 m) orthogonal aerial images have a low spectral resolution (Red-Green-Blue), high spatial resolution (~1.9 pixels cm-2, ~1.3 cm length) and flexible temporal resolution (monthly). The method is successfully applied in two lowland rivers to quantify four key properties of vegetated rivers: vegetation cover, patch size distribution, biomass and hydraulic resistance. The main advantages are that the method is: (i) suitable for continuous and discontinuous vegetation covers (ii) of very-high spatial and flexible temporal resolution, (iii) relatively fast compared to conventional ground survey methods, (iv) non-destructive, (v) relatively cheap and easy to use, and (vi) the software is widely available and similar open source alternatives exist. The study area should be less than 10 m wide and the prevailing light conditions and water turbidity levels should be sufficient to look into the water. Further improvements of the images processing are expected in the automatic delineation and classification of the vegetation patches

Value of histopathologic analysis of subcutis excisions by general practitioners

BACKGROUND: Only around 60% of skin lesions excised by GPs are referred to a pathologist. Clinical diagnoses of skin excisions by GPs may not be very accurate. Subcutis excisions are rarely done by GPs, and there is hence little information in the literature on the histopathological yield of subcutis excisions by GPs with regard to malignancies. The aim of this study was to evaluate the yield of histopathological investigation of a relatively large group of subcutis excisions by GPs, with special emphasis on discrepancies between clinical and histopathological diagnoses of malignancy. METHODS: We investigated a series of 90 subcutis excisions, which was derived from a database of consecutive GP submissions from the years 1999–2000 where in the same time period 4595 skin excisions were performed by the same group of GPs. This underlines the apparent reluctance of GPs to perform subcutis excisions. RESULTS: The final diagnosis was benign in 88 cases (97.8%) and malignant in 2 cases (2.2%). Seven cases had no clinical diagnosis, all of which were benign. Of the 83 clinically benign cases, 81 (97.6%) were indeed benign and 2 (2.4%) were malignant: one Merkel cell carcinoma and one dermatofibrosarcoma protuberans. The former was clinically thought to be a lipoma, and the latter a trichilemmal cyst. The dermatofibrosarcoma protuberans presented at the age of 27, and the Merkel cell carcinoma at the age of 60. Both were incompletely removed and required re-excision by a surgical oncologist. CONCLUSION: Histopathological investigation of subcutis excisions by GPs yields unexpected and rare malignancies in about 2% of cases that may initially be excised inadequately. Based on these data, and because of the relatively rareness of these type of excisions, it could be argued that it may be worthwhile to have all subcutis excisions by GPs routinely investigated by histopathology

Development of an ex vivo model to study the response of skeletal muscle to transverse mechanical loading

Development of an ex vivo model to study the response of skeletal muscle to transverse mechanical loading. M. Graser, A. Wark, S. Day, A. Buis, The soft tissues in our body, particularly skeletal muscles, commonly experience physical stress. In most cases, the muscles can maintain the balance between damage and regeneration. However, this balance might be disturbed in certain populations that are subject to extreme cases  of overload or repeated impact, like individuals spinal cord injury [3] or transtibial prosthetic users [2].To characterise critical loading scenarios, experimental models of skeletal muscle under mechanical loading are necessary [4, 5]. A controllable environment as well as the reproduction of the highly hierarchical structure of skeletal muscle are thereby desirable. We therefore developed an ex vivo model to study the response of skeletal muscle to transverse mechanical loading. MethodsSoleus and extensor digitorum longus muscles of male Sprague Dawley rats were dissected and transversely compressed (2mm indenter, 9-32kPa) (Fig. 1). Control tissues were held under the same conditions for the same time without loading. Subsequently, tissue viability and morphology were assessed through standard histological procedures using Procion Yellow MX4R and Live-or-Dye™ for fluorescent dead cell staining as well as H&E. Additionally, biochemical changes of cell and tissue damaged were visualised with multiphoton Raman microscopy of unstained samples.Figure 1: Schematic of ex vivo model. A: Skeletal muscle dissection; B: Mechanical loading; C: Image analysis for cell damage; D: Data analysis to establish the relationship between loading conditions and cell damage.Results & DiscussionWhilst control samples showed only minor loss in cell viability throughout the experimental time frame (max. 3h), mechanical damage in loaded tissues was readily distinguishable. Imaging revealed a partial loss of cross-striations, disorganised and disrupted muscle fibres, increased interstitial space, and loss of cell viability. With careful control of the experimental setup, detailed imaging of local cellular damage in response to loading conditions could be obtained. ConclusionOur ex vivo model of skeletal muscle for transverse mechanical loading is suitable for quantifying cellular damage. Looking at this microscale will provide important insights into the adaptive capabilities of skeletal muscle. This can provide the basis for further research into the role of soft tissue deformation in limb pain and ulcer formation and could inform future directions for socket design and fit

Risk Factors of Mortality in Severely-malnourished Children Hospitalized with Diarrhoea

This case-control study was conducted in the Dhaka Hospital of ICDDR,B to identify the risk factors of mortality in severely-malnourished children hospitalized with diarrhoea. One hundred and three severely-malnourished children (weight-for-age <60% of median of the National Center for Health Statistics standard) who died during hospitalization were compared with another 103 severely-malnourished children who survived. These children were aged less than three years and admitted to the hospital during 1997. On admission, characteristics of the fatal cases and non-fatal controls were comparable, except for age. The median age of the cases and controls were six and eight months respectively (p=0.05). Patients with low pulse rate or imperceptible pulse had three times the odds of death compared to the control group (p<0.01). The presence of clinical septicaemia and clinical severe anaemia had 11.7 and 4.2 times the odds of death respectively (p<0.01). Patients with leukocytosis (>15,000/cm3) had 2.5 times the odds of death (p<0.01). Using logistic regression, clinical septicaemia [adjusted odds ratio (AOR)=8.8, confidence interval (CI) 3.7-21.1, p=0.01], hypothermia (AOR=3.5, CI 1.3-9.4, p<0.01), and bronchopneumonia (AOR=3.0, CI 1.2-7.3, p<0.01) were identified as the significant risk factors of mortality. Severely-malnourished children (n=129) with leukocytosis, imperceptible pulse, pneumonia, septicaemia, and hypothermia had a high risk of mortality. The identified risk factors can be used as a prognostic guide for patients with diarrhoea and severe malnutrition

The costs of complications and unplanned readmissions after pancreatoduodenectomy for pancreatic and periampullary tumors:Results from a single academic center

SIMPLE SUMMARY: Complications lead to unplanned readmissions (UR) and are reported to be associated with a two- to threefold increase in hospital admission costs. Since healthcare costs are increasing worldwide, cost containment is the major challenge for future healthcare. In the literature, there are only a few studies that analysed hospital costs after pancreatoduodenectomy (PD). In this study, we aimed to create an understanding of the costs of complications and UR in patients who underwent a PD. ABSTRACT: Background/Objectives: Complications after pancreatoduodenectomy (PD) lead to unplanned readmissions (UR), with a two- to threefold increase in admission costs. In this study, we aimed to create an understanding of the costs of complications and UR in this patient group. Furthermore, we aimed to generate a detailed cost overview that can be used to build a theoretical model to calculate the cost efficacy for prehabilitation. Methods: A retrospective cohort analysis was performed using the Dutch Pancreatic Cancer Audit (DPCA) database of patients who underwent a PD at our institute between 2013 and 2017. The total costs of the index hospital admission and UR related to the PD were collected. Results: Of the 160 patients; 35 patients (22%) had an uncomplicated course; 87 patients (54%) had minor complications, and 38 patients (24%) had severe complications. Median costs for an uncomplicated course were EUR 25.682, and for a complicated course, EUR 32.958 (p = 0.001). The median costs for minor complications were EUR 30.316, and for major complications, EUR 42.664 (p = 0.001). Costs were related to the Comprehensive Complication Index (CCI). The median costs of patients with one or more UR were EUR 41.199. Conclusions: Complications after PD led to a EUR 4.634–EUR 16.982 (18–66%) increase in hospital costs. A UR led to a cost increase of EUR 12.567 (44%). Since hospital costs are directly related to the CCI, reduction in complications will lead to cost-effectiveness

Selective serotonin reuptake inhibitors in the treatment of generalized anxiety disorder

Selective serotonin reuptake inhibitors have proven efficacy in the treatment of panic disorder, obsessive–compulsive disorder, post-traumatic stress disorder and social anxiety disorder. Accumulating data shows that selective serotonin reuptake inhibitor treatment can also be efficacious in patients with generalized anxiety disorder. This review summarizes the findings of randomized controlled trials of selective serotonin reuptake inhibitor treatment for generalized anxiety disorder, examines the strengths and weaknesses of other therapeutic approaches and considers potential new treatments for patients with this chronic and disabling anxiety disorder

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81