226 research outputs found
Intrahepatic heteropolymerization of M and Z alpha-1-antitrypsin
The α-1-antitrypsin (or alpha-1-antitrypsin, A1AT) Z variant is the primary cause of severe A1AT deficiency and forms polymeric chains that aggregate in the endoplasmic reticulum of hepatocytes. Around 2%-5% of Europeans are heterozygous for the Z and WT M allele, and there is evidence of increased risk of liver disease when compared with MM A1AT individuals. We have shown that Z and M A1AT can copolymerize in cell models, but there has been no direct observation of heteropolymer formation in vivo. To this end, we developed a monoclonal antibody (mAb2H2) that specifically binds to M in preference to Z A1AT, localized its epitope using crystallography to a region perturbed by the Z (Glu342Lys) substitution, and used Fab fragments to label polymers isolated from an MZ heterozygote liver explant. Glu342 is critical to the affinity of mAb2H2, since it also recognized the mild S-deficiency variant (Glu264Val) present in circulating polymers from SZ heterozygotes. Negative-stain electron microscopy of the Fab2H2-labeled liver polymers revealed that M comprises around 6% of the polymer subunits in the MZ liver sample. These data demonstrate that Z A1AT can form heteropolymers with polymerization-inert variants in vivo with implications for liver disease in heterozygous individuals
A modular, time-independent, path-based controller for assist- as- needed rehabilitative exoskeletons
After a traumatic event (e.g., orthopedic or neu-rological injury), engaging in activities of daily living (ADLs) encourages the individual and aids in relearning functional motions for the impaired limb. The outcome of robot-assisted rehabilitation is inherently connected to the control strategy adopted in the training sessions. Here, the authors propose a time-independent path-tracking controller with impedance modulation that provides assistance and guidance along the path. Based on the assist-as-needed (AAN) paradigm, a task-space-based force field controller was designed to cooperatively support the individual during training. The authors will illus-trate the flexibility of the proposed control strategy, showcasing its adaptability to various exoskeletons with minimal or minor adjustments. Leveraging the control versatility, the authors propose the application of this methods to two case studies: Float upper limb and TWIN lower limb exoskeletons
Clorexidina e gel di fluoro: riduzione dello streptococcus mutans nel paziente special needs
Utilizzo delle cellule staminali nella terapia di pazienti con esiti di labiopalatoschisi
Clinical evaluation of the efficacy of a combined zinc gluconate and cetylpyridinium chloride oral rinse toothpaste use in preventing gingivitis insurgence in fixed orthodontic patients
Co-occurrence of malignant neoplasm and Hyperostosis Frontalis Interna in an Iron Age individual from Münsingen-Rain (Switzerland): A multi-diagnostic study
Objective: To re-analyze one of the oldest cases of malignant bone neoplasm with different analytical techniques. Material: The available skeletal remains of grave 138 (G138) from the Iron Age necropolis of Münsingen-Rain (Switzerland, 420–240 BC). Methods: The bones are analyzed by means of morphological, radiographic, histological, and biogeochemical methods. Results: The individual, a male aged between 35–50 years old, presents morphologically and radiographically a previously described coral-like bone neoformation on the proximal left humerus. The new analyses highlight previously undocumented coarse bone proliferation on the left scapula and lobular apposition on the endocranial surface of the frontal bone. The histological analysis of the humerus shows a ‘lace-like’ pattern of osteoid deposition without lamellation. Conclusions: Our data support a diagnosis of osteoblastic malignant neoplasm, probably an osteosarcoma or, more likely, a dedifferentiated chondrosarcoma for the humerus and scapula, and of hyperostosis frontalis interna on the frontal. The co-presence of a malignant neoplasm and hyperostosis frontalis interna may be related to a hormonal imbalance, a possibility also suggested by atypical funerary treatment. Significance: This study confirms G138 as one of the oldest cases of malignant bone neoplasm, adds new paleopathological data on this individual, and demonstrates the advantages of a multidisciplinary approach. Limitations: The discussion of the pathological changes is limited by the representation and preservation of the skeletal elements. Suggestion for Future Research: Biomolecular and protein biomarkers analyses may help to refine the diagnostic conclusions
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