BB0172, a Borrelia burgdorferi Outer Membrane Protein That Binds Integrin Α3Β1

Lyme disease is a multisystemic disorder caused by Borrelia burgdorferi infection. Upon infection, some B. burgdorferi genes are upregulated, including members of the microbial surface components recognizing adhesive matrix molecule (MSCRAMM) protein family, which facilitate B. burgdorferi adherence to extracellular matrix components of the host. Comparative genome analysis has revealed a new family of B. burgdorferi proteins containing the von Willebrand factor A (vWFA) domain. In the present study, we characterized the expression and membrane association of the vWFA domain-containing protein BB0172 by using in vitro transcription/translation systems in the presence of microsomal membranes and with detergent phase separation assays. Our results showed evidence of BB0172 localization in the outer membrane, the orientation of the vWFA domain to the extracellular environment, and its function as a metal ion-dependent integrin-binding protein. This is the first report of a borrelial adhesin with a metal ion-dependent adhesion site (MIDAS) motif that is similar to those observed in eukaryotic integrins and has a similar function

Bilateral acute angle closure glaucoma as a presentation of isolated microspherophakia in an adult: case report

BACKGROUND: Bilateral simultaneous angle closure glaucoma is a rare entity. To our knowledge this is the first reported case of bilateral acute angle-closure glaucoma secondary to isolated microspherophakia in an adult. CASE PRESENTATION: A 45-year-old woman presented with bilateral acute angle closure glaucoma, with a patent iridotomy in one eye. Prolonged miotic use prior to presentation had worsened the pupillary block. The diagnosis was not initially suspected, and the patient was subjected to pars-plana lensectomy and anterior vitrectomy for a presumed ciliary block glaucoma. The small spherical lens was detected intraoperatively, and spherophakia was diagnosed in retrospect. She had no systemic features of any of the known conditions associated with spherophakia. Pars-plana lensectomy both eyes controlled the intraocular pressure successfully. CONCLUSION: This case demonstrates the importance of considering the diagnosis of isolated microspherophakia in any case of bilateral acute angle closure glaucoma. Lensectomy appears to be an effective first-line strategy for managing these patients

Evaluation of an online Diabetes Needs Assessment Tool (DNAT) for health professionals: a randomised controlled trial

Background: Continuous medical education is traditionally reliant to a large extent on self-directed learning based on individuals' perceived learning priorities. Evidence suggests that this ability to self-assess is limited, and more so in the least competent. Therefore, it may be of benefit to utilise some form of external assessment for this purpose. Many diabetes educational programmes have been introduced, but few have been assessed for their benefit in a systematic manner. As diabetes is an increasingly prevalent disease, methods for the dissemination and understanding of clinical guidelines need to be explored for their effectiveness. This paper describes the study design of a randomised controlled trial to evaluate the effectiveness of using an interactive online Diabetes Needs Assessment Tool (DNAT), that builds a learning curriculum based on identified knowledge gaps, compared with conventional self-directed learning. The study assesses the effect of these interventions on health professionals' knowledge of diabetes management, evaluates the acceptability of this process of learning and self-reported changes in clinical practice as a result of this novel educational process. Methods: Following a baseline assessment, participants will be randomised to undergo a 4-month learning period where they will either be given access to the diabetes learning modules alone (control group) or a Diabetes Needs Assessment Tool (DNAT) plus the diabetes learning modules (intervention group). On completion of the DNAT, a personalised learning report will be created for each participant identifying needs alongside individualised recommendations of the most appropriate learning modules to meet those requirements. All participants will complete a Diabetes Knowledge Test before and immediately after the allocated learning and the primary outcome will be the state of knowledge at 4 months. Learners will also be surveyed immediately after the learning period to assess the acceptability of the learning formats and the perceived usefulness and usability of the materials. After a further month, all learners will receive a series of questions to evaluate self-reported changes in clinical practice as a result of this educational experience and asked to include specific examples of any changes in their diabetes care practice

Evaluation of an online interactive Diabetes Needs Assessment Tool (DNAT) versus online self-directed learning: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Methods for the dissemination, understanding and implementation of clinical guidelines need to be examined for their effectiveness to help doctors integrate guidelines into practice. The objective of this randomised controlled trial was to evaluate the effectiveness of an interactive online Diabetes Needs Assessment Tool (DNAT) (which constructs an e-learning curriculum based on individually identified knowledge gaps), compared with self-directed e-learning of diabetes guidelines.</p> <p>Methods</p> <p>Health professionals were randomised to a 4-month learning period and either given access to diabetes learning modules alone (control group) or DNAT plus learning modules (intervention group). Participants completed knowledge tests before and after learning (primary outcome), and surveys to assess the acceptability of the learning and changes to clinical practice (secondary outcomes).</p> <p>Results</p> <p>Sixty four percent (677/1054) of participants completed both knowledge tests. The proportion of nurses (5.4%) was too small for meaningful analysis so they were excluded. For the 650 doctors completing both tests, mean (SD) knowledge scores increased from 47.4% (12.6) to 66.8% (11.5) [intervention group (n = 321, 64%)] and 47.3% (12.9) to 67.8% (10.8) [control group (n = 329, 66%)], (ANCOVA p = 0.186). Both groups were satisfied with the usability and usefulness of the learning materials. Seventy seven percent (218/284) of the intervention group reported combining the DNAT with the recommended reading materials was "<it>very useful"/"useful"</it>. The majority in both groups (184/287, 64.1% intervention group and 206/299, 68.9% control group) [95% CI for the difference (-2.8 to 12.4)] reported integrating the learning into their clinical practice.</p> <p>Conclusions</p> <p>Both groups experienced a similar and significant improvement in knowledge. The learning materials were acceptable and participants incorporated the acquired knowledge into practice.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN67215088">ISRCTN67215088</a></p

Distant metastases of a squamous cell carcinoma of the tongue in peripheral skeletal muscles and adjacent soft tissues

A 66-year-old female patient was admitted to our department with a large tumor of the tongue measuring 10 cm in diameter. The tumor occupied nearly the entire oral cavity and showed exophytic and ulcerative areas. Histological analysis revealed a low grade squamous cell carcinoma (SCC) of the tongue. Bilateral enlarged cervical lymphatic masses were also present. The extent of the tumor infiltration was assessed by fluoro-2-deoxy-glucose-positron emission tomography (PET) scans showing an elevated activity of the tracer corresponding to the assumed cervical metastases. Additionally, pulmonary metastases were identified. Contrast enhanced computed tomography (CT) scans showed metastases in the soft tissues of the abdomen, legs and arms. Foci of distant metastases were found in the left upper anterior thoracal wall, near the intraabdominal portion of the aorta, near the right iliac crest and in both the right vastus medialis- and adductor magnus muscles. The final diagnosis was a T4N3M1(G3)(C3) SCC of the tongue with multiple distant thoracal, abdominal and intramuscular metastases. The survival expectancy was five weeks, and the patient finally deceased by cardiopulmonary complications

Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation

The NF-κB/REL-family of transcription factors plays a central role in coordinating the expression of a wide variety of genes controlling immune responses including autoimmunity of the central nervous system (CNS). The inactive form of NF-κB consists of a heterodimer which is complexed with its inhibitor, IκB. Conditional knockout-mice for IκBα in myeloid cells (lysMCreIκBαfl/fl) have been generated and are characterized by a constitutive activation of NF-κB proteins allowing the study of this transcription factor in myelin-oligodendrocyte-glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), a well established experimental model for autoimmune demyelination of the CNS

Valgus and varus deformity after wide-local excision, brachytherapy and external beam irradiation in two children with lower extremity synovial cell sarcoma: case report

BACKGROUND: Limb-salvage is a primary objective in the management of extremity soft-tissue sarcoma in adults and children. Wide-local excision combined with radiation therapy is effective in achieving local tumor control with acceptable morbidity and good functional outcomes for most patients. CASE PRESENTATION: Two cases of deformity after wide-local excision, brachytherapy and external beam irradiation for lower-extremity synovial cell sarcoma are presented and discussed to highlight contributing factors, time course of radiation effects and orthopedic management. In an effort to spare normal tissues from the long-term effects of radiation therapy, more focal irradiation techniques have been applied to patients with musculoskeletal tumors including brachytherapy and conformal radiation therapy. As illustrated in this report, the use of these techniques results in the asymmetric irradiation of growth plates and contributes to the development of valgus or varus deformity and leg-length discrepancies. CONCLUSIONS: Despite good functional outcomes, progressive deformity in both patients required epiphysiodesis more than 3 years after initial management. There is a dearth of information related to the effects of radiation therapy on the musculoskeletal system in children. Because limb-sparing approaches are to be highlighted in the next generation of cooperative group protocols for children with musculoskeletal tumors, documentation of the effects of surgery and radiation therapy will lead to improved decision making in the selection of the best treatment approach and in the follow-up of these patients

Arsenic Trioxide Enhances the Radiation Sensitivity of Androgen-Dependent and -Independent Human Prostate Cancer Cells

Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells) and PC-3 cells (androgen-independent human prostate cancer cells) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with arsenic trioxide (ATO) and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS) generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer

Lung function associated gene Integrator Complex subunit 12 regulates protein synthesis pathways

Background: Genetic studies of human lung function and Chronic Obstructive Pulmonary Disease have identified a highly significant and reproducible signal on 4q24. It remains unclear which of the two candidate genes within this locus may regulate lung function: GSTCD, a gene with unknown function, and/or INTS12, a member of the Integrator Complex which is currently thought to mediate 3'end processing of small nuclear RNAs.Results: We found that, in lung tissue, 4q24 polymorphisms associated with lung function correlate with INTS12 but not neighbouring GSTCD expression. In contrast to the previous reports in other species, we only observed a minor alteration of snRNA processing following INTS12 depletion. RNAseq analysis of knockdown cells instead revealed dysregulation of a core subset of genes relevant to airway biology and a robust downregulation of protein synthesis pathways. Consistent with this, protein translation was decreased in INTS12 knockdown cells. In addition, ChIPseq experiments demonstrated INTS12 binding throughout the genome, which was enriched in transcriptionally active regions. Finally, we defined the INTS12 regulome which includes genes belonging to the protein synthesis pathways.Conclusion: INTS12 has functions beyond the canonical snRNA processing. We show that it regulates translation by regulating the expression of genes belonging to protein synthesis pathways. This study provides a detailed analysis of INTS12 activities on a genome-wide scale and contributes to the biology behind the genetic association for lung function at 4q24.</p