Citations

Polylactic acid (PLA) has a long history in medical applications. Reinforced PLA has the potential to be used in the medical applications that require high mechanical strength such as coronary stents and bone fixation devices. Halloysite nanotube (HNT) has received considerable attention recently due to its tubular structure, high aspect ratio, high mechanical strength, thermal stability, biocompatibility and sustained drug releasing properties. Halloysite has been investigated in compounding with many polymers. However, the research in compounding halloysite with biodegradable materials for use in biological applications is sparse. In this study various weight fractions of HNT was compounded with the biodegradable polymer PLA using a melt compounding method. Tensile test, Fourier infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), contact angle test, scanning electron microscopy (SEM), void content and thermogravimetric analysis (TGA) were carried out to study the PLA/HNT composite. Tensile test results indicated that Young's modulus and stiffness of PLA were enhanced with the addition of HNT; FTIR spectra showed the interaction between the PLA and HNT; whereas contact angle measurements indicated that the wettability of the PLA/HNT composite was not affected by the addition of HNT. However, the thermal stability of PLA was adversely effected by the addition of HNT which may be related to the presence of voids between the polymer and matrix. Nevertheless, the reinforced PLA/HNT composite, which maintains the surface characteristics, may prove beneficial for use in biological applications. POLYM. COMPOS., 38:2166–2173, 2017. © 2015 Society of Plastics Engineers

ABSTRACT The FilmArray respiratory panel (FARP) reliably and rapidly identifies 17 viruses and 3 bacterial pathogens. A nasopharyngeal swab FARP (NP FARP) is performed for many patients with respiratory symptoms. For patients who are acutely ill or immunocompromised or fail to improve, a bronchoalveolar lavage sample FARP (BAL FARP) is performed in addition to the NP FARP. To date, no studies have compared the yield of a BAL FARP with that of an NP FARP. We retrospectively studied all patients who had a BAL FARP within 7 days after an NP FARP between June 2013 and May 2014. Demographic information, comorbidities, FARP results, and all microbiologic data from BAL fluid were collected. Eighty-six patients had a BAL FARP performed within 7 days (mean, 1.6; median, 1) after an NP FARP. Of these, 66 (77%) had concordant BAL and NP FARP results: 15 (23%) had the same pathogen identified from the NP and BAL FARPs, and 51 (77%) had concordant negative FARP results. In 18 of the 86 patients (21%), a pathogen was detected from the NP FARP; of these, 15 (83%) had a concordant match on a subsequent BAL FARP, and the remaining 3 had negative BAL FARPs. In 17 of the 86 patients (20%), pathogens were identified from the BAL FARPs that were not detected by the NP FARPs; of these, 16 (94%) had initial negative NP FARPs. The data suggest that once a pathogen is identified by an NP FARP, a subsequent BAL FARP is unlikely to add new microbiologic information. However, a BAL FARP may provide new, useful microbiologic information when performed within 7 days after a negative NP FARP.

Abstract Alternative NF-κB signaling is crucial for B cell activation and Ig production, and it is mainly regulated by the inhibitor of κ B kinase (IKK) regulatory complex. Dysregulation of alternative NF-κB signaling in B cells could therefore lead to hyperactive B cells and Ig overproduction. In our previous, study we found that deleted in breast cancer 1 (DBC1) is a suppressor of the alternative NF-κB pathway to attenuate B cell activation. In this study, we report that loss of DBC1 results in spontaneous overproduction of Ig in mice after 10 mo of age. Using a double mutant genetic model, we confirm that DBC1 suppresses B cell activation through RelB inhibition. At the molecular level, we show that DBC1 interacts with alternative NF-κB members RelB and p52 through its leucine zipper domain. In addition, phosphorylation of DBC1 at its C terminus by IKKα facilitates its interaction with RelB and IKKα, indicating that DBC1-mediated suppression of alternative NF-κB is regulated by IKKα. Our results define the molecular mechanism of DBC1 inhibition of alternative NF-κB activation in suppressing B cell activation.

Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn2+for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2+. Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of-function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the utility of this knowledge for orthopedic applications and bone tissue engineering.

Abstract Background Gastrointestinal ( GI ) manifestations are found in Ehlers Danlos syndrome ( EDS ) hypermobility subtype ( HM ). We aimed to assess associations between EDS HM and other EDS subtypes with GI manifestations. Methods We reviewed medical records of EDS patients evaluated at Mayo Clinic's Medical Genetics Clinic 1994–2013. We extracted information regarding EDS subtypes, GI manifestations, and treatments. Key Results We identified 687 patients; 378 (56%) had associated GI manifestations (female 86.8%, diagnosis mean age 29.6 years). Of the patients identified, 58.9% (43/73) had EDS classic, 57.5% (271/471) EDS HM , 47.3% (27/57) EDS vascular subtypes. In addition, 86 patients had EDS that could not be classified in any of those three subtypes. Commonest GI symptoms were: abdominal pain (56.1%), nausea (42.3%), constipation (38.6%), heartburn (37.6%), and irritable bowel syndrome‐like symptoms (27.5%). Many GI symptoms were commoner in EDS HM than the other subtypes together. Among 37.8% of the 378 patients who underwent esophagogastroduodenoscopy, the commonest abnormalities were gastritis, hiatal hernia and reflux esophagitis. Abnormal gastric emptying was observed in 22.3% (17/76): 11.8% delayed and 10.5% accelerated. Colonic transit was abnormal in 28.3% (13/46): 19.6% delayed and 8.7% accelerated. Rectal evacuation disorder was confirmed in 18/30 patients who underwent anorectal manometry. Angiography showed aneurysms in abdominal vessels in EDS vascular type. Proton pump inhibitors (38%) and drugs for constipation (23%) were the most commonly used medications. A minority underwent colectomy (2.9%) or small bowel surgery (4%). Conclusions & Inferences EDS HM and other subtypes should be considered in patients with chronic functional GI symptoms and abdominal vascular lesions.

Abstract Purpose: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. Experimental design: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m2 i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. Results: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%–43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%–44%) randomized to rituximab. Six (17%; 95% CI, 7%–34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%–29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27+) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. Conclusions: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab. Clin Cancer Res; 22(2); 319–27. ©2015 AACR.

In the anatomy laboratory, skill remains a critical component to unlocking the true value of learning from cadaveric dissection. However, there is little if any room for provision of instruction in proper dissection technique. We describe how near‐peer instructors designed a supplemental learning activity to enhance the dissection experience for first‐year medical students. This study aimed to evaluate the efficacy of this curriculum in improving participants' understanding of dissection technique and its impact on perceived challenges associated with the anatomy course. Curriculum was designed under faculty guidance and included didactic sessions, low‐fidelity models, dissection, student presentations, and clinical correlations. Participants' (n = 13) knowledge of basic dissection techniques and concepts were assessed before the selective, and both participants' and nonparticipants' (n = 39) knowledge was assessed at the end of week one and week seven of the anatomy course. Scores were compared using repeated measures ANOVA followed by post hoc t‐tests. Thirteen deidentified reflective essays were reviewed by four independent reviewers for themes that aligned with learning objectives. Participants in the selective course scored higher on assessment of dissection techniques and concepts one week after the selective compared to both nonparticipants and their own baseline scores before the selective. Analysis of student reflections resulted in four themes: confidence with dissection skill, sharing resources and transfer of knowledge, learning environment, and psychological impact of perceived challenges of the anatomy course. Near‐peer driven supplemental exercises are effective in facilitating dissection skills. This dissection primer increases student confidence and alleviates apprehension associated with anatomy courses. Clin. Anat. 28:985–993, 2015. © 2015 Wiley Periodicals, Inc.

Background Migraine attacks manifest with hypersensitivities to light, sound, touch and odor. Some people with migraine have photosensitivity between migraine attacks, suggesting persistent alterations in the integrity of brain regions that process light. Although functional neuroimaging studies have shown visual stimulus induced “hyperactivation” of visual cortex regions in migraineurs between attacks, whether photosensitivity is associated with alterations in brain structure is unknown. Methods Levels of photosensitivity were evaluated using the Photosensitivity Assessment Questionnaire in 48 interictal migraineurs and 48 healthy controls. Vertex-by-vertex measurements of cortical thickness were assessed in 28 people with episodic migraine who had interictal photosensitivity (mean age = 35.0 years, SD = 12.1) and 20 episodic migraine patients without symptoms of interictal photosensitivity (mean age = 36.0 years, SD = 11.4) using a general linear model design. Results Migraineurs have greater levels of interictal photosensitivity relative to healthy controls. Relative to migraineurs without interictal photosensitivity, migraineurs with interictal photosensitivity have thicker cortex in several brain areas including the right lingual, isthmus cingulate and pericalcarine regions, and the left precentral, postcentral and supramarginal regions. Conclusion Episodic migraineurs with interictal photosensitivity have greater cortical thickness in the right parietal-occipital and left fronto-parietal regions, suggesting that persistent light sensitivity is associated with underlying structural alterations.