Lowrykerr8701
WuXiBody is a novel bispecific antibody (bsAb) platform developed by WuXi Biologics. It enables almost any monoclonal antibody (mAb) sequence pair to be assembled into a bispecific construct. BsAbs based on WuXiBody can adopt either asymmetric or symmetric format. WuXiBody's unique design not only ensures desired chain pairing but also facilitates removal of potential product-related impurities. In this work, demonstrated with four WuXiBody-based bsAbs (two asymmetric and two symmetric ones), we showed that Protein A followed by anion exchange (AEX) and mixed-mode chromatography (i.e., Capto MMC ImpRes or Capto adhere ImpRes) can be a potential platform approach for WuXiBody purification. BACKGROUND Abusive head trauma (AHT) in children older than 1 and younger than 5 years old is thought uncommon and rarely studied. OBJECTIVE This study estimates national incidence and case fatality rate of abusive head trauma (AHT), and evaluates differences by age, sex, race, and region, with a focus on children of 2-4 years. PARTICIPANTS AND SETTING Hospital discharges were extracted from The Healthcare Cost and Utilization Project's Kids' Inpatient Database from 2000, 2003, 2006, 2009, and 2012 using the CDC's narrow definition of AHT. METHODS Survey-weighted chi-square tests were used to assess differences in incidence and case fatality rates. RESULTS The average annual incidence per 100,000 children was highest in less then 1 year-olds (27), followed by age 1 (4), age 2 (3), and age 3-4 (1). Average annual incidence varied significantly by sex (p = 0.0001), race (p less then 0.0001), and region (p = 0.0002) within each age category. The average annual case fatality rate increased significantly with age, with a rate of 0.10 among children age less then 1 year, 0.15 for age 1, 0.23 for age 2, and 0.20 for age 3-4 years. The average annual case fatality rate was higher in the South (0.12) than West (0.10), Midwest (0.09), and Northeast (0.08) among children less then 1 year of age. CONCLUSIONS Black and Hispanic children and hospitals in the Midwest experienced higher incidence of AHT than White children and Northeast hospitals, respectively, especially in cases less then 1 year of age. Case fatality rates increased significantly with age, and the South experienced the highest rates for infants less then 1 year. BACKGROUND Heat shock protein beta-1 (HSPB1) is a ubiquitously expressed molecular chaperone that is important in protecting cells against cellular injury. Mutations in this protein are known to cause autosomal dominant hereditary distal axonal neuropathies, including Charcot Marie Tooth disease type 2F (CMT2F) and distal hereditary motor neuropathy (dHMN). However, patients with HSPB1 mutations have also been described with upper motor neuron signs. We present five patients with mutations in HSPB1 who presented with a range of clinical phenotypes related to different patterns of motor neuron dysfunction. Three of these mutations have not been previously reported. METHODS Patients were seen at our neuromuscular or amyotrophic lateral sclerosis (ALS) clinics. Gene sequencing was carried out as part of diagnostic investigations. Detailed clinical and electrophysiologic data was collected. RESULTS Five patients had variants of HSPB1. Three patients had a hereditary length-dependent sensori-motor axonal neuropathy consistent with Charcot Marie Tooth type 2 (CMT2); two of these patients carried novel mutations in the C-terminal region (p.Glu186* and p.Pro170Thr). One patient had the clinical picture of ALS and a novel missense mutation (p.Arg27Leu) in the N-terminal region. Another patient had the phenotype of hereditary spastic paraparesis (HSP) associated with a missense mutation (p.Gly84Arg) already described in families with CMT or dHMN. CONCLUSION This study describes three novel mutations of HSPB1 and describes two patients with upper motor neurone signs associated with HSPB1 mutations. Crown V. All rights reserved.Beta-cyclodextrin (β-CD) is an oligosaccharide commonly used to improve the aqueous solubility of lipophilic drugs (e.g., dexamethasone, DEX). Here we present the development of a drug delivery system to provide sustained release of DEX by β-CD-inclusion complex (IC) to amplify the mineralization capacity of stem cells from human-extracted deciduous teeth (SHEDs) as a potential direct pulp capping strategy. First, IC of DEX (DEX-CD-IC) was synthesized with β-CD. To confirm DEX-CD-IC complex formation, X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analyses were performed. XRD data indicated that IC formation was achieved due to formation of a new crystalline structure, whereas FTIR revealed the presence of the IC from the shifting of the peaks of each component in DEX-CD-IC. Then, electrospun poly(lactic-co-glycolic acid, PLGA) fibers (PLGA/DEX-CD-IC) were processed by varying the concentration of DEX-CD-IC (5%, 10 %, and 15 %). The release of DEX from fibers was determined by ultraperformance liquid chromatography for 28 days. Thanks to the solubility enhancement of DEX by IC, electrospun PLGA/DEX-CD-IC fibers released DEX in a more sustained fashion compared to PLGA/DEX fibers. No deleterious effect was found in terms of SHEDs' proliferation when cultured with or on electrospun fibers, regardless of the IC presence. Importantly, a more pronounced odontogenic differentiation was stimulated by electrospun fibers loaded with the lowest DEX-CD-IC concentration (5%), as a result of the sustained DEX release. In sum, PLGA/DEX-CD-IC fibers have great potential in vital dental pulp therapy, owing to its sustained DEX release, cytocompatibility, and odontogenic differentiation capacity. OBJECTIVES The present study purposed to observe the response of comorbidities of temporomandibular disorders (TMD) including migraine and cervical dysfunction after painful TMD treatment. DESIGN A total of 187 patients were included 45 had no symptoms related to the painful TMD and migraine (Control), 52 had the painful TMD only (pTMD), 47 had the painful TMD that occurred earlier than the migraine (TMD1ST), and 43 had the migraine that occurred earlier than the painful TMD (MIG1ST). All patients were diagnosed based on the Research Diagnostic Criteria for Temporomandibular Disorders and International Classification of Headache Disorders, 3rd edition. Head and neck posture were assessed using lateral cephalogram. Myofascial trigger points were evaluated in the two masticatory and four cervical muscles. Stabilization splint therapy and physical therapy were applied to all patients for six months. RESULTS MIG1ST showed lesser improvement of the intensity of the orofacial and neck pain and forward head posture than the pTMD and TMD1ST after 6 months TMD treatment. In addition, lesser degree of symptomatic progress of intensity, duration and frequency of the migraine in MIG1ST was detected than in TMD1ST after 6 months TMD treatment. CONCLUSION The effects of TMD management on symptomatic changes of its comorbidities including the migraine and cervical dysfunction could be determined by onset order of comorbid conditions relative to TMD. Cannabis-based medications are being increasingly used for the treatment of different clinical conditions. Among all galenic formulations, olive oil extracts from medical Cannabis are the most prescribed ones for their easy preparation and usage. A great variety of methods have been described so far for the extraction of medical Cannabis oils to reach a high yield of Δ9-tetrahydrocannabinol (Δ9-THC), but poor attention has been paid to the preservation of the terpene fraction from the plant, which may contribute to the overall bioactivity of the extracts. In this context, the present study was aimed at the chemical characterization of different medical Cannabis oils prepared by following both innovative and existing extraction protocols, with particular attention to cannabinoids and terpenes, in order to set up a suitable method to obtain an extract rich in these chemical classes. In particular, six different extraction procedures were followed, based on different techniques, of which all but one included a decarboxylation of the plant material. The profile of cannabinoids was studied in detail by means of HPLC-ESI-MS/MS, while terpenes were characterized by means both GC-MS and GC-FID techniques coupled with solid-phase microextraction operated in the head-space mode (HS-SPME). An innovative method that is based on the extraction of the oil by dynamic maceration at room temperature from plant inflorescences, which were partially decarboxylated in a closed system at a moderate temperature and partially pre-extracted with ethanol, produced similar yields of bioactive compounds as that obtained by using a microwave-assisted distillation of the essential oil from the plant material, in combination with a maceration extraction of the oil from the residue. Both these new methods provided a higher efficiency over already existing extraction procedures of medical Cannabis oils and they can be applied to obtain a product with a high therapeutic value. Silk sericin (SS) is, together with silk fibroin (SF), one of the two proteins forming the silkworm cocoon. SS is ideal ingredient for cosmetic applications in the formulation of specific products for skin care and hair due to its peculiar physical-chemical composition. SS also showed a great potential in different pharmacological and biotechnological applications, as anticancer drug, anticoagulant, cell culture additive, wound healing agent and drug delivery carrier. Reasons for SS use in biomedical applications derive from its physical-chemical composition. As a consequence, a detailed characterization of SS in terms of average molecular weight, molecular weight distribution and hydro/lipophilic character is crucial to properly address and assess its quality, cosmetic or pharmacological use. In this study, the application of different and complementary chromatographic modes allows a detailed investigation of SS protein isolated from wastewater using two diverse extraction methods. read more Hydrophilic interaction liquid chromatography (HILIC using an AdvanceBio Glycan Map column) and reverse phase (RP using Symmetry300 C18 column) were applied to intact protein characterization to derive data on protein hydrophilicity and on hydrophobic components of the two SS preparations (SS#1 and SS#2). A higher hydrophilic character of SS#1 was observed by HILIC trace, coherently with the preparation method used, while no significant differences in hydrophobicity were detectable in the RPLC separations. Size distribution was also defined by using a SEC-UV-MS method (using TSKgel SuperSW2000 column) properly optimized to maximize both the size selectivity and the method sensitivity. Taken together, the chromatographic data allowed to better characterize the SS samples obtained by different extraction methods, and the structural properties were correlated to their biological activities. Animal epizootics show widely destructive effect on livestock value chains in sub Saharan Africa, pushing many smallholders into poverty and discouraging investments. Hence, African swine fever (ASF) has been playing a deeply depressing role on swine value chain of Benin since its first occurrence in the country in 1997. Exchanges between actors are fundamental among stakeholders for the overall performance of a value chain and is key in the way these can respond to challenges, as epizootic threats. The present study describes how stakeholders of the swine value chain interact in the diffusion of innovative practices facing an outbreak of ASF. In seven districts, focus groups were first organized with stakeholders to identify changes and other reactions that ensued from a recent ASF outbreak in Benin. In a second step, individual semi-structured interviews were conducted, following a respondent-driven sampling, to collect the contact information needed for social network analysis. The influence of actors' characteristics on their degree centrality was tested through multiple linear regression model.