Do parents of children with congenital malformations have a higher cancer risk? A nationwide study in Denmark

To investigate whether parents of children with congenital malformations more often developed cancer after birth of the child, a population-based case-control study in Denmark was undertaken. By linking the Cancer Registry with the Central Population Registry, we identified 8783 cancer patients having their first child born between 1977 and 1995 before the cancer was diagnosed. Parents of 41 206 firstborn children of a 10% random sample of newborns from the Birth Registry between 1980 and 1995 were identified as controls. We obtained malformation diagnoses of children of cases and controls by linking to the Hospital Discharge Registry. We estimated the association between malformation and cancer by using logistic regression, adjusting for maternal age at birth and sex of child. We found no increased risk of cancer in parents having children with malformations in general, but a higher cancer risk in parents of children born with cleft lip/palate, odds ratio (OR) for all cancer=1.8 (95% confidence interval 1.0–3.2), OR for lymphomas=4.2 (1.3–13.5) and OR for leukaemia=8.1 (2.0–33.7). This association was not restricted to cancer cases diagnosed shortly after birth of the child. Our results suggest a common genetic association between these diseases, but further studies are needed

Abiotrophia defectiva knee prosthesis infection: A case report

<p>Abstract</p> <p>Background</p> <p><it>Abiotrophia </it>species have rarely been implicated in osteoarticular infections. We report one case of an <it>A. defectiva </it>knee prosthesis infection.</p> <p>Case presentation</p> <p>A 71-year-old man of Italian origin presented with pain and swelling of the knee four years after the implantation of a total knee replacement prosthesis. While standard culturing of the synovial fluid resulted in no isolation of microorganisms, the direct inoculation of the synovial fluid into a rich culture medium resulted in the identification of <it>A. defectiva </it>by polymerase chain reaction sequencing. Repeated attempts of culturing microorganisms from blood were negative, and echocardiograms and colonoscopies were unremarkable. High-dose amoxicillin for nine months and a two-stage replacement of the knee prosthesis led to full patient recovery by the time of the 12-month follow-up examination.</p> <p>Conclusions</p> <p>Because <it>Abiotrophia </it>spp. are fastidious microorganisms, it is likely that cases of <it>Abiotrophia </it>orthopedic infection are misdiagnosed as culture-negative infections. Direct inoculation of synovial fluids into rich broth medium and further polymerase chain reaction-based detection of culture-negative synovial fluids are key tests for accurate documentation and detection of these infections.</p

Sonication is superior to scraping for retrieval of bacteria in biofilm on titanium and steel surfaces in vitro

Background and purpose Low-virulence implant infections are characterized by bacterial colonization of the implant with subsequent biofilm formation. In these cases, soft tissue biopsies often prove to be culture negative. Consequently, detachment of the causative adherent bacteria is crucial for correct microbiological diagnosis. Using an in vitro model, we compared 4 methods of biofilm sampling from metal surfaces

Does long-term care use within primary health care reduce hospital use among older people in Norway? A national five-year population-based observational study

<p>Abstract</p> <p>Background</p> <p>Population ageing may threaten the sustainability of future health care systems. Strengthening primary health care, including long-term care, is one of several measures being taken to handle future health care needs and budgets. There is limited and inconsistent evidence on the effect of long-term care on hospital use. We explored the relationship between the total use of long-term care within public primary health care in Norway and the use of hospital beds when adjusting for various effect modifiers and confounders.</p> <p>Methods</p> <p>This national population-based observational study consists of all Norwegians (59% women) older than 66 years (N = 605676) (13.2% of total population) in 2002-2006. The unit of analysis was defined by municipality, age and sex. The association between total number of recipients of long-term care per 1000 inhabitants (LTC-rate) and hospital days per 1000 inhabitants (HD-rate) was analysed in a linear regression model. Modifying and confounding effects of socioeconomic, demographic and geographic variables were included in the final model. We defined a difference in hospitalization rates of more than 1000 days per 1000 inhabitants as clinically important.</p> <p>Results</p> <p>Thirty-one percent of women and eighteen percent of men were long-term care users. Men had higher HD-rates than women. The crude association between LTC-rate and HD-rate was weakly negative. We identified two effect modifiers (age and sex) and two strong confounders (travel time to hospital and mortality). Age and sex stratification and adjustments for confounders revealed a positive statistically significant but not clinically important relationship between LTC-rates and hospitalization for women aged 67-79 years and all men. For women 80 years and over there was a weak but negative relationship which was neither statistically significant nor clinically important.</p> <p>Conclusions</p> <p>We found a weak positive adjusted association between LTC-rates and HD-rates. Opposite to common belief, we found that increased volume of LTC by itself did not reduce pressure on hospitals. There still is a need to study integrated care models for the elderly in the Norwegian setting and to explore further why municipalities far away from hospital achieve lower use of hospital beds.</p

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Increased permeability-oedema and atelectasis in pulmonary dysfunction after trauma and surgery: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Trauma and surgery may be complicated by pulmonary dysfunction, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), but the mechanisms are incompletely understood.</p> <p>Methods</p> <p>We evaluated lung capillary protein permeability non-invasively with help of the ⁶⁷Ga-transferrin pulmonary leak index (PLI) technique and extravascular lung water (EVLW) by the transpulmonary thermal-dye dilution technique in consecutive, mechanically ventilated patients in the intensive care unit within 24 h of direct, blunt thoracic trauma (n = 5, 2 with ARDS), and within 12 h of indirect trauma by transhiatal oesophagectomy (n = 8), abdominal surgery for cancer (n = 6) and bone surgery (n = 4). We studied transfusion history, haemodynamics, oxygenation and mechanics of the lungs. The lung injury score (LIS, 0–4) was calculated. Plain radiography was also done to judge densities and atelectasis.</p> <p>Results</p> <p>The PLI and EVLW were elevated above normal in 61 and 30% of patients, respectively, and the PLI directly related to the number of red cell concentrates given (r_s= 0.69, P < 0.001), without group differences. Oxygenation, lung mechanics, radiographic densities and thus the LIS (1.0 [0.25–3.5]) did not relate to PLI and EVLW. However, groups differed in oxygenation and airway pressures and impaired oxygenation related to the number of radiographic quadrants with densities (r_s= 0.55, P = 0.007). Thoracic trauma patients had a worse oxygenation requiring higher airway pressures and thus higher LIS than the other patient groups, unrelated to PLI and EVLW but attributable to a higher cardiac output and thereby venous admixture. Finally, patients with radiographic signs of atelectasis had more impaired oxygenation and more densities than those without.</p> <p>Conclusion</p> <p>The oxygenation defect and radiographic densities in mechanically ventilated patients with pulmonary dysfunction and ALI/ARDS after trauma and surgery are likely caused by atelectasis rather than by increased permeability-oedema related to red cell transfusion.</p

From L-Dopa to Dihydroxyphenylacetaldehyde: A Toxic Biochemical Pathway Plays a Vital Physiological Function in Insects

One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD) family based on extremely high sequence homology (∼70%) with dopa decarboxylase (Ddc), was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA) directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects

Infliximab Induces Clonal Expansion of γδ-T Cells in Crohn's Disease: A Predictor of Lymphoma Risk?

BACKGROUND: Concominant with the widespread use of combined immunotherapy in the management of Crohn's disease (CD), the incidence of hepato-splenic gamma-delta (γδ)-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process resulting in the selection of malignant γδ-T cell clones. We hypothesised that repeated infusion of anti-TNF-α agents may induce clonal selection and that concurrent treatment with immunomodulators further predisposes patients to γδ-T cell expansion. METHODOLOGY/PRINCIPAL FINDINGS: We investigated dynamic changes in the γδ-T cells of patient with CD following treatment with infliximab (Remicade®; n=20) or adalimumab (Humira®; n=26) using flow cytometry. In patients with a high γδ-T cell level, the γδ-T cells were assessed for clonality. Of these 46 CD patients, 35 had a γδ-T cells level (mean 1.6%) comparable to healthy individuals (mean 2.2%), and 11 CD patients (24%) exhibited an increased level of γδ-T cells (5-15%). In the 18 patients also receiving thiopurines or methotrexate, the average baseline γδ-T cell level was 4.4%. In three male CD patients with a high baseline value, the γδ-T cell population increased dramatically following infliximab therapy. A fourth male patient also on infliximab monotherapy presented with 20% γδ-T cells, which increased to 25% shortly after treatment and was 36% between infusions. Clonality studies revealed an oligoclonal γδ-T cell pattern with dominant γδ-T cell clones. In support of our clinical findings, in vitro experiments showed a dose-dependent proliferative effect of anti-TNF-α agents on γδ-T cells. CONCLUSION/SIGNIFICANCE: CD patients treated with immunomodulators had constitutively high levels of γδ-T cells. Infliximab exacerbated clonal γδ-T cell expansion in vivo and induced γδ-T cell proliferation in vitro. Overall, young, male CD patients with high baseline γδ-T cell levels may be at an increased risk of developing malignant γδ-T cell lymphomas following treatment with anti-TNF-α agents