Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy

Background: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. Results: A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 μg/g (p < 0.0001), reflecting severe exocrine pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p < 0.0001). Neither pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. Conclusion: The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyrigh

Autoimmune lymphoproliferative syndrome (ALPS) in a child from consanguineous parents: a dominant or recessive disease?

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by autoimmune features and lymphoproliferations and is generally caused by defective Fas-mediated apoptosis. This report describes a child with clinical features of ALPS without detectable Fas expression on freshly isolated blood leukocytes. Detection of FAS transcripts via real-time quantitative PCR made a severe transcriptional defect unlikely. Sequencing of the FAS gene revealed a 20-nucleotide duplication in the last exon affecting the cytoplasmic signaling domain. The patient was homozygous for this mutation, whereas the consanguineous parents and the siblings were heterozygous. The patient reported here is a human homologue of the Fas-null mouse, inasmuch as she carries an autosomal homozygous mutation in the FAS gene and she shows the severe and accelerated ALPS phenotype. The heterozygous family members did not have the ALPS phenotype, indicating that the disease-causing FAS mutation in this family is autosomal recessive

Cloning and expression of Rift Valley fever virus nucleocapsid (N) protein and evaluation of a N-protein based indirect ELISA for the detection of specific IgG and IgM antibodies in domestic ruminants

Serodiagnosis of Rift Valley fever (RVF) currently relies on the use of live or inactivated whole virus as antigens. The recombinant nucleocapsid (N) protein of RVF virus was tested for diagnostic applicability in an indirect enzyme-linked immunosorbent assay (I-ELISA), using sera from experimentally infected sheep (n = 128), vaccinated sheep (n = 240), and field-collected sera from sheep (n = 251), goats (n = 362) and cattle (n = 100). The N-protein based I-ELISA performed at least as good as VN and HI tests. In goat the diagnostic sensitivity (D-Sn) and specificity (D-Sp) of the I-ELISA was 100% when using the anti-species IgG conjugate. Using protein G as a detection system, the D-Sn and D-Sp in goats were 99.4% and 99.5%, in sheep field sera both 100%, in cattle 100% and 98.3%, respectively. The I-ELISA based on recombinant N-protein has the potential to complement the traditional assays for serodiagnosis of RVF. Advantages of the N-protein are its safety, stability and cost-effectiveness in use and production.The authors wish to thank the staff of the Cytokine Center (Utrecht University), Special Pathogens Unit (National Institute for Communicable Diseases) and Veterinary Faculty of the Eduardo Mondlane University for technical assistance in this study. The work was sponsored by the International Foundation for Science (IFS grant B/3212-1), Sweden and by a MacGillavry PhD Fellowship of the Royal Dutch Academy of Science (KNAW) and Utrecht University, The Netherlands

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95% CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95% CI ¼ 0.54 to 0.98). Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Radiographic, computed tomographic, and arthroscopic findings in Labrador Retrievers with medial coronoid disease

Objective To describe the radiographic, computed tomographic (CT), and arthroscopic findings in different age groups of Labrador Retrievers diagnosed with medial coronoid disease (MCD), and to compare the ulnar subtrochlear sclerosis (STS) observed on radiographs with the ratio between the mean attenuation of the ulnar subtrochlear bone and the mean attenuation of the cortical bone measured on CT. Study Design Prospective clinical study. Animals Dogs (n = 31; 31 elbow joints) and 6 healthy Labrador Retrievers (6 elbow joints). Methods Radiographic, CT, and intraoperative arthroscopic images (2008–2012) were evaluated. Statistical analysis was performed for the descriptive study to evaluate the difference in findings between age groups and to investigate the correlation between radiographic and CT evaluated ulnar STS. Results Ulnar STS (87.6%) was the most common radiographic findings in dogs ≤12 months and blurring of the cranial edge of the medial coronoid process (MCP; 66.7%) was the most common radiographic findings in dogs >12 months. MCP fragmentation was the most common CT finding in both age groups (93.8% [≤12 months]; 66.7% [>12 months]). A displaced fragment (68.8%) was the most common arthroscopic finding in dogs ≤12 months whereas osteochondromalacia (53.3%) was the most common finding in dogs >12 months. Sensitivity of radiography in detecting MCD was 93.8% (≤12 months) and 73.3% (>12 months) and for CT was 93.8% (≤12 months) and 66.7% (>12 months). Radiographic evaluated ulnar STS was strongly correlated with CT evaluated ulnar STS. Conclusion Wide ranges of radiographic, CT, and arthroscopic findings in Labrador Retrievers diagnosed with medial coronoid disease were identified

Evaluation of instrumented shoes for ambulatory assessment of ground reaction forces

Currently, force plates or pressure sensitive insoles are the standard tools to measure ground reaction forces and centre of pressure data during human gait. Force plates, however, impose constraints on foot placement, and the available pressure sensitive insoles measure only one component of force. In this study, shoes instrumented with two force transducers measuring forces and moments in three dimensions were evaluated. Technical performance was assessed by comparing force measurement and centre of pressure reconstructions of the instrumented shoes against a force plate. The effect of the instrumented shoes on gait was investigated using an optical tracking system and a force plate. Instrumented shoes were compared against normal shoes and weighted shoes. The ground reaction force measured with force plate and instrumented shoes differed by 2.2 ± 0.1% in magnitude and by 3.4 ± 1.3° in direction. The horizontal components differed by 9.9 ± 3.8% in magnitude and 26.9 ± 10.0° in direction. Centre of pressure location differed by 13.7 ± 2.4 mm between measurement systems. A MANOVA repeated measures analysis on data of seven subjects, revealed significant differences in gait pattern between shoe types (p ≤ 0.05). A subsequent univariate analysis showed significant differences only in maximum ground reaction force but these could not be attributed to specific shoe types by pair-wise comparison. This study indicates that shoes instrumented with force transducers can be a valuable alternative to current measurement systems if accurate sensing of position and orientation of the force transducers is improved. They are applicable in ambulatory settings and suitable for inverse dynamics analysis

Active involvement of people with dementia: a systematic review of studies developing supportive technologies

Although there are promising benefits of supportive technology in dementia care, use of these technologies is still limited. It is challenging for researchers and developers in this field to actively involve people with dementia in development. This review updates and builds on existing knowledge by including a contemporary and relevant perspective. This perspective was gained by including search words and search databases from the field of Human Computer Interaction (HCI) and Design, as these fields were expected to supply novel insights in the complex task of actively involving people with dementia in developing supportive technologies. A total of 49 out of 3456 studies were included which describe the development of a great variety of technologies. Often people with dementia were involved in the generative or evaluative phase of the development. Interviews and observations were most commonly used methods. In seven articles the people with dementia were co-designers. This literature review reflects that people with dementia can influence the development of technology in regards to content, design, and even the initial idea, although the impact on how they experience their own involvement remains largely unknown. There is a lack of specific knowledge on appropriate methods and materials for active involvement of people with dementia in supportive technology development, even when including articles from the field of HCI and Design. Future research is needed to further appreciate and improve the desired role of people with dementia in meaningful technology development