The crossroads between infection and bone loss

Bone homeostasis, based on a tight balance between bone formation and bone degradation, is affected by infection. On one hand, some invading pathogens are capable of directly colonizing the bone, leading to its destruction. On the other hand, immune mediators produced in response to infection may dysregulate the deposition of mineral matrix by osteoblasts and/or the resorption of bone by osteoclasts. Therefore, bone loss pathologies may develop in response to infection, and their detection and treatment are challenging. Possible biomarkers of impaired bone metabolism during chronic infection need to be identified to improve the diagnosis and management of infection-associated osteopenia. Further understanding of the impact of infections on bone metabolism is imperative for the early detection, prevention, and/or reversion of bone loss. Here, we review the mechanisms responsible for bone loss as a direct and/or indirect consequence of infection.This article is a result of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunologicalm, and infectious diseases (NORTE-01-0145-FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). A.C.G. is supported by a Junior Investigator Contract under the program CEEIND2017, from Fundação para a Ciência e Tecnologia (Portugal)

Developing a Global Healthcare Innovation Index

Our understanding of medicine is being revolutionised by the pace of science. But not all the potential innovations in life sciences and medical technology are taken up into everyday practice in healthcare, even when they are shown to be beneficial. For the poorest people in the world, many innovations are not accessible because they are either unaffordable or unsuitable for their health systems. Tackling this gap requires the development of appropriate and affordable health technologies and novel business models. In the more advanced health systems there is a disconnection between the effort on research and development (R&D) and how much of this makes it into mainstream healthcare practice. Even the most evidence-based and affordable innovations can fail or are only taken up patchily, whether we compare across countries, or between localities or health organisations within countries. And technological innovation can be a problem for those responsible for paying for health systems. New technologies often increase costs because they allow us to treat more people for a longer part of their lives. Yet the general view amongst politicians, managers and others involved in healthcare is that health systems across the world need new thinking. They are increasingly facing escalating demand from an ageing population and the growing incidence of chronic disease. Healthcare is consuming an ever-increasing share of gross domestic product (GDP). The search is on for ways of providing the best quality healthcare as affordably as possible. The health technology industries – pharmaceutical and biotechnology, medical devices, information technology and the built environment (design, engineering and construction) – drive much of the innovation that takes place in healthcare. They are very big business. Collectively these companies have global revenues in the order of USD 2 trillion a year, about a quarter of overall global spending on healthcare. But they too are experiencing a changing landscape – an evolving market for their products, a changing balance of power across health systems as governments and payers seek to control costs, hence pressure on their business models. Innovation is regarded by economists and politicians as one of the main drivers of economic growth. It helps to explain why some companies, regions and countries perform better than others in terms of higher productivity and income. For companies involved in the health technology sector, and governments in countries where they are located, there is concern to ensure that their business models are sustainable and continue to successfully deliver new products to the market

A novel PAX5 rearrangement in TCF3-PBX1 acute lymphoblastic leukemia: a case report.

BACKGROUND: Chromosome translocations are a hallmark of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Additional genomic aberrations are also crucial in both BCP-ALL leukemogenesis and treatment management. Herein, we report the phenotypic and molecular cytogenetic characterization of an extremely rare case of BCP-ALL harboring two concomitant leukemia-associated chromosome translocations: t(1;19)(q23;q13.3) and t(9;17)(p13;q11.2). Of note, we described a new rearrangement between exon 6 of PAX5 and a 17q11.2 region, where intron 3 of SPECC1 is located. This rearrangement seems to disrupt PAX5 similarly to a PAX5 deletion. Furthermore, a distinct karyotype between diagnosis and relapse samples was observed, disclosing a complex clonal evolution during leukemia progression. CASE PRESENTATION: A 16-year-old boy was admitted febrile with abdominal and joint pain. At clinical investigation, he presented with anemia, splenomegaly, low white blood cell count and 92% lymphoblast. He was diagnosed with pre-B ALL and treated according to high risk GBTLI-ALL2009. Twelve months after complete remission, he developed a relapse in consequence of a high central nervous system and bone marrow infiltration, and unfortunately died. CONCLUSIONS: To our knowledge, this is the first report of a rearrangement between PAX5 and SPECC1. The presence of TCF3-PBX1 and PAX5-rearrangement at diagnosis and relapse indicates that both might have participated in the malignant transformation disease maintenance and dismal outcome

In vitro and in vivo performance of methacrylated gellan gum hydrogel formulations for cartilage repair

Methacrylated gellan gum (GGMA) formulation is proposed as a second‐generation hydrogel for controlled delivery of cartilage‐forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof‐of‐concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non‐treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non‐treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno‐free biomaterial to be used with chondrogenic cells for a cost‐effective treatment of focal chondral lesions

DIAGNÓSTICOS DE ENFERMAGEM NAS COMPLICAÇÕES EM SALA DE RECUPERAÇÃO ANESTÉSICA

<!-- /* Font Definitions */ @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-1610611985 1107304683 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:PT-BR; mso-fareast-language:PT-BR;} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:10.0pt; mso-ansi-font-size:10.0pt; mso-bidi-font-size:10.0pt;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> This is a descriptive, exploratory study with a qualitative method and non-experimental design, with analysis of absolute and relative frequency of data. It shows how to identify nursing diagnoses according to NANDA Taxonomy II in Post Anesthesia Care Unit (PACU). The sample consisted of 30 adult patients undergoing elective surgery with general anesthesia, and evaluation of physical conditions according to American Society of Anesthesiologists (ASA 1). The field of study was the PACU, which has 8 beds in a mixed network hospital in the city of Santos. Data were collected through a structured method, with data on gender, age, medical diagnoses, intervention-surgical anesthetic, surgical time, anesthetic time, vital signs including blood pressure at admission, assessment of the index of Aldrete KrouliK; and complications such as nausea, vomiting and pain. After the analysis of the nursing problems, nursing diagnoses were identified, with the greatest frequency being hypothermia, nausea, and acute pain.  Este es un estudio descriptivo, exploratorio, con método cualitativo y rasgo no empírico, con análisis de frecuencia absoluta y relativa de los datos. Presenta como objetivo identificar los diagnósticos de enfermería según la Taxonomía II de la NANDA, en la Sala de Recuperación Post-Anestésica (SRPA). La muestra estaba constituida por 30 enfermos adultos, sometidos a cirugía selectiva, con anestesia general y evaluación de las condiciones físicas Americam Society of Anesthesiologists (ASA1). El campo de estudio fue la SPRA, la cual cuenta con 8 camas de un hospital de la red mixta de la ciudad de Santos. Los datos fueron colectados a través de un instrumento estructurado, con datos referentes al sexo, edad, diagnóstico médico, intervención anestésico quirúrgica, tiempo quirúrgico, tiempo anestésico, signos vitales, incluyendo verificación de la tensión arterial en la internación, índices de Aldrete Kroulik y complicaciones como náusea, vómito y dolor. Tras el análisis de los problemas de enfermería, fueron identificados los diagnósticos de enfermería, siendo los de mayor frecuencia la hipotermia, náusea y dolor agudo.Este é um estudo descritivo, exploratório, com método quantitativo e delineamento não experimental, com análise de freqüência absoluta e relativa dos dados. Apresenta como objetivo identificar os diagnósticos de enfermagem, segundo a Taxonomia II da NANDA, na Sala de Recuperação Pós-Anestésica (SRPA). A amostra foi constituída de 30 pacientes adultos, submetidos à cirurgia eletiva, com anestesia geral, e avaliação das condições físicas Americam Society of Anesthesiologists (ASA 1). O campo de estudo foi a SRPA, a qual conta com 8 leitos, de um Hospital da rede mista da cidade de Santos. Os dados foram coletados por meio de um instrumento estruturado, com dados referentes ao sexo, idade, diagnóstico médico, intervenção anestésico-cirúrgica, tempo cirúrgico, tempo anestésico, sinais vitais incluindo verificação de pressão arterial na internação, avaliação do índice de Aldrete KrouliK; e complicações como náusea, vômito e dor. Após o levantamento dos problemas de enfermagem, foram identificados os diagnósticos de enfermagem, sendo os maior freqüência a hipotermia, náusea e dor aguda. &nbsp

Health-related quality of life in patients with venous leg ulcer treated in primary care in Brazil and Portugal

Background Venous ulcers constitute an important public health problem as they can cause disability with consequences for multiple dimensions of quality of life. Objective To describe the quality of life in patients with venous leg ulcer treated in primary care in two cities from Brazil and Portugal. Methods This was a cross-sectional comparative study with a non-probabilistic sample of 171 patients with venous leg ulcers who were treated in primary care in two cities from Brazil and Portugal, namely, Natal and Évora. A form covering sociodemographic and health data and the Medical Outcomes Study 36-Item Short-Form Health Survey were used, and descriptive and inferential analyses were performed. Results Significant differences in age and income were observed between the two samples. Patients with venous leg ulcer from Brazil had lower income and were younger than those from Portugal. Quality of life scores were significantly higher in Portugal for the physical aspects, pain, and social functioning, among domains, and for the physical health dimension and total score of QOL. Conclusion The quality of life was better in Portugal than in Brazil and the differences between the countries need further investigation

Serum amyloid A proteins reduce bone mass during mycobacterial infections

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFN gamma- and TNF alpha-dependent manner. IFN gamma produced during infection enhanced macrophage TNF alpha secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.This article is a result of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145-FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was supported by KOG-202108-00929 from the European Haematology Society, awarded to AG. Work in the MS lab was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028955 (PTDC/SAU-INF/28955/2017). AG and MS are supported by an Individual Scientific Employment contract (CEECIND/00048/2017; CEECIND/00241/2017 respectively). DS acknowledges the Portuguese Foundation for Science and Technology (FCT) for the Post-Doc fellowship (SFRH/BPD/115341/2016). RP, DS and AF have PhD grants (SFRH/BD/145217/2019; SFRH/BD/143536/2019; 2020.05949.BD, respectively) financed by FCT

Markedly Divergent Tree Assemblage Responses to Tropical Forest Loss and Fragmentation across a Strong Seasonality Gradient

We examine the effects of forest fragmentation on the structure and composition of tree assemblages within three seasonal and aseasonal forest types of southern Brazil, including evergreen, Araucaria, and deciduous forests. We sampled three southernmost Atlantic Forest landscapes, including the largest continuous forest protected areas within each forest type. Tree assemblages in each forest type were sampled within 10 plots of 0.1 ha in both continuous forests and 10 adjacent forest fragments. All trees within each plot were assigned to trait categories describing their regeneration strategy, vertical stratification, seed-dispersal mode, seed size, and wood density. We detected differences among both forest types and landscape contexts in terms of overall tree species richness, and the density and species richness of different functional groups in terms of regeneration strategy, seed dispersal mode and woody density. Overall, evergreen forest fragments exhibited the largest deviations from continuous forest plots in assemblage structure. Evergreen, Araucaria and deciduous forests diverge in the functional composition of tree floras, particularly in relation to regeneration strategy and stress tolerance. By supporting a more diversified light-demanding and stress-tolerant flora with reduced richness and abundance of shade-tolerant, old-growth species, both deciduous and Araucaria forest tree assemblages are more intrinsically resilient to contemporary human-disturbances, including fragmentation-induced edge effects, in terms of species erosion and functional shifts. We suggest that these intrinsic differences in the direction and magnitude of responses to changes in landscape structure between forest types should guide a wide range of conservation strategies in restoring fragmented tropical forest landscapes worldwide