A model of impairment and functional limitation in rheumatoid arthritis

BACKGROUND: We have previously proposed a theoretical model for studying physical disability and other outcomes in rheumatoid arthritis (RA). The purpose of this paper is to test a model of impairment and functional limitation in (RA), using empirical data from a sample of RA patients. We based the model on the disablement process framework. METHODS: We posited two distinct types of impairment in RA: 1) Joint inflammation, measured by the tender, painful and swollen joint counts; and 2) Joint deformity, measured by the deformed joint count. We hypothesized direct paths from the two impairments to functional limitation, measured by the shirt-button speed, grip strength and walking velocity. We used structural equation modeling to test the hypothetical relationships, using empirical data from a sample of RA patients recruited from six rheumatology clinics. RESULTS: The RA sample was comprised of 779 RA patients. In the structural equation model, the joint inflammation impairment displayed a strong significant path toward the measured variables of joint pain, tenderness and swelling (standardized regression coefficients 0.758, 0.872 and 0.512, P ≤ 0.001 for each). The joint deformity impairment likewise displayed significant paths toward the measured upper limb, lower limb, and other deformed joint counts (standardized regression coefficients 0.849, 0.785, 0.308, P ≤ 0.001 for each). Both the joint inflammation and joint deformity impairments displayed strong direct paths toward functional limitation (standardized regression coefficients of -0.576 and -0.564, respectively, P ≤ 0.001 for each), and explained 65% of its variance. Model fit to data was fair to good, as evidenced by a comparative fit index of 0.975, and the root mean square error of approximation = 0.058. CONCLUSION: This evidence supports the occurrence of two distinct impairments in RA, joint inflammation and joint deformity, that together, contribute strongly to functional limitations in this disease. These findings may have implications for investigators aiming to measure outcome in RA

Draft genome sequence of Wickerhamomyces anomalus LBCM1105, isolated from cachaça fermentation

Wickerhamomyces anomalus LBCM1105 is a yeast isolated from cachaça distillery fermentation vats, notable for exceptional glycerol consumption ability. We report its draft genome with 20.5x in-depth coverage and around 90% extension and completeness. It harbors the sequences of proteins involved in glycerol transport and metabolism.The authors gratefully acknowledge Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE) and the Centro Nacional de Pesquisa em Energia e Materiais (CNPEM) for support with the sequencing of LBCM1105. This work was supported by CAPES/Brazil (PNPD 2755/2011; PCF-PVE 021/2012), by CNPq (Brazil), processes 304815/2012 (research grant) and 305135/2015-5, and by AUXPE-PVES 1801/2012 (Process 23038.015294/2016-18) from Brazilian Government and by UFOP. C.L. is supported by the strategic program UID/BIA/04050/2013 [POCI-01-0145-FEDER-007569] funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional de Competitividade e Internacionalizacao (POCI). DMRP is a fellow from the CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) - Brazil (310080/2018-5)

Molecular basis of targeted therapy in T/NKcell lymphoma/leukemia: A comprehensive genomic and immunohistochemical analysis of a panel of 33 cell lines

T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways. The study identified TP53, NOTCH1 and DNMT3A as the most frequently mutated genes. We also found common alterations in JAK/STAT and epigenetic pathways. Immunohistochemical analysis showed nuclear accumulation of MYC (in 85% of the cases), NFKB (62%), p-STAT (44%) and p-MAPK (30%). This panel of cell lines captures the complexity of T/NK-cell lymphoproliferative processes samples, with the partial exception of AITL cases. Integrated mutational and immunohistochemical analysis shows that mutational changes cannot fully explain the activation of key survival pathways and the resulting phenotypes. The combined integration of mutational/expression changes forms a useful tool with which new compounds may be assayed

Looking through the 'window of opportunity': is there a new paradigm of podiatry care on the horizon in early rheumatoid arthritis?

Over the past decade there have been significant advances in the clinical understanding and care of rheumatoid arthritis (RA). Major paradigm changes include earlier disease detection and introduction of therapy, and 'tight control' of follow-up driven by regular measurement of disease activity parameters. The advent of tumour necrosis factor (TNF) inhibitors and other biologic therapies have further revolutionised care. Low disease state and remission with prevention of joint damage and irreversible disability are achievable therapeutic goals. Consequently new opportunities exist for all health professionals to contribute towards these advances. For podiatrists relevant issues range from greater awareness of current concepts including early referral guidelines through to the application of specialist skills to manage localised, residual disease activity and associated functional impairments. Here we describe a new paradigm of podiatry care in early RA. This is driven by current evidence that indicates that even in low disease activity states destruction of foot joints may be progressive and associated with accumulating disability. The paradigm parallels the medical model comprising early detection, targeted therapy, a new concept of tight control of foot arthritis, and disease monitoring

The skull of Epidolops ameghinoi from the early Eocene Itaboraí fauna, southeastern Brazil, and the affinities of the extinct marsupialiform order Polydolopimorphia

The skull of the polydolopimorphian marsupialiform Epidolops ameghinoi is described in detail for the first time, based on a single well-preserved cranium and associated left and right dentaries plus additional craniodental fragments, all from the early Eocene (53-50 million year old) Itaboraí fauna in southeastern Brazil. Notable craniodental features of E. ameghinoi include absence of a masseteric process, very small maxillopalatine fenestrae, a prominent pterygoid fossa enclosed laterally by a prominent ectopterygoid crest, an absent or tiny transverse canal foramen, a simple, planar glenoid fossa, and a postglenoid foramen that is immediately posterior to the postglenoid process. Most strikingly, the floor of the hypotympanic sinus was apparently unossified, a feature found in several stem marsupials but absent in all known crown marsupials. "Type II" marsupialiform petrosals previously described from Itaboraí plausibly belong to E. ameghinoi; in published phylogenetic analyses, these petrosals fell outside (crown-clade) Marsupialia. "IMG VII" tarsals previously referred to E. ameghinoi do not share obvious synapomorphies with any crown marsupial clade, nor do they resemble those of the only other putative polydolopimorphians represented by tarsal remains, namely the argyrolagids. Most studies have placed Polydolopimorphia within Marsupialia, related to either Paucituberculata, or to Microbiotheria and Diprotodontia. However, diprotodonty almost certainly evolved independently in polydolopimorphians, paucituberculatans and diprotodontians, and Epidolops does not share obvious synapomorphies with any marsupial order. Epidolops is dentally specialized, but several morphological features appear to be more plesiomorphic than any crown marsupial. It seems likely Epidolops that falls outside Marsupialia, as do morphologically similar forms such as Bonapartherium and polydolopids. Argyrolagids differ markedly in their known morphology from Epidolops but share some potential apomorphies with paucituberculatans. It is proposed that Polydolopimorphia as currently recognised is polyphyletic, and that argyrolagids (and possibly other taxa currently included in Argyrolagoidea, such as groeberiids and patagoniids) are members of Paucituberculata. This hypothesis is supported by Bayesian non-clock phylogenetic analyses of a total evidence matrix comprising DNA sequence data from five nuclear protein-coding genes, indels, retroposon insertions and morphological characters: Epidolops falls outside Marsupialia, whereas argyrolagids form a clade with the paucituberculatans Caenolestes and Palaeothentes, regardless of whether the Type II petrosals and IMG VII tarsals are used to score characters for Epidolops or not. There is no clear evidence for the presence of crown marsupials at Itaboraí, and it is possible that the origin and early evolution of Marsupialia was restricted to the "Austral Kingdom" (southern South America, Antarctica, and Australia)

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)