Creation of Laryngeal Grafts from Primary Human Cells and Decellularized Laryngeal Scaffolds

Current reconstruction methods of the laryngotracheal segment fail to replace the complex functions of the human larynx. Bioengineering approaches to reconstruction have been limited by the complex tissue compartmentation of the larynx. We attempted to overcome this limitation by bio-engineering laryngeal grafts from decellularized canine laryngeal scaffolds recellularized with human primary cells under one uniform culture medium condition. First, we generated laryngeal scaffolds with preserved glycosaminoglycan content and biomechanical properties by detergent perfusion-decellularization over nine days. We proofed biocompatibility by absence of a CD3 lymphocyte response to subcutaneously implanted scaffolds in immune-competent rats. We then developed a uniform culture medium that strengthened the endothelial barrier over 5 days after an initial growth phase. Simultaneously, this culture medium supported airway epithelial cell and skeletal myoblast growth while maintaining their full differentiation and maturation potential. We then applied the uniform culture medium composition to whole laryngeal scaffolds seeded with endothelial cells from both carotid arteries and external jugular veins and generated re-endothelialized arterial and venous vascular beds. Under the same culture medium condition, we bio-engineered epithelial monolayers onto laryngeal mucosa and repopulated intrinsic laryngeal muscle. We were then able to demonstrate early muscle formation in heterotopic transplantations in immuno-deficient mice. The model supported the formation of three humanized laryngeal tissue compartments under one uniform culture condition, possibly a key factor in developing, complex, multicellular, ready-to-transplant tissue grafts

Pain and analgesia in critical illness

A detecção, quantificação e tratamento da dor em doente crítico é, à longa data, uma preocupação dos clínicos que tra- balham em Unidades de Cuidados Intensivos. Não obstante, a dor é frequente em doentes críticos, independentemente do seu critério de admissão. Os autores apresentam uma revisão sobre analgesia em doente critico enfatizando o recurso a escalas apropriadas para o seu diagnóstico, quantificação e avaliação de terapêuticas efetuadas. São descritas as abordagens farmacológicas (sistémicas e regionais) recomendadas e discute-se a evolução do evento doloroso agudo a crónico em contexto de cuidados intensivos

Comparative complete scheme and booster effectiveness of COVID‐19 vaccines in preventing SARS‐CoV‐2 infections with SARS‐CoV‐2 Omicron (BA.1) and Delta (B.1.617.2) variants: A case–case study based on electronic health records

Background: Information on vaccine effectiveness in a context of novel variants of concern (VOC) emergence is of key importance to inform public health policies. This study aimed to estimate a measure of comparative vaccine effectiveness between Omicron (BA.1) and Delta (B.1.617.2 and sub-lineages) VOC according to vaccination exposure (primary or booster). Methods: We developed a case-case study using data on RT-PCR SARS-CoV-2-positive cases notified in Portugal during Weeks 49-51, 2021. To obtain measure of comparative vaccine effectiveness, we compared the odds of vaccination in Omicron cases versus Delta using logistic regression adjusted for age group, sex, region, week of diagnosis, and laboratory of origin. Results: Higher odds of vaccination were observed in cases infected by Omicron VOC compared with Delta VOC cases for both complete primary vaccination (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.8 to 2.4) and booster dose (OR = 5.2; 95% CI: 3.1 to 8.8), equivalent to reduction of vaccine effectiveness from 44.7% and 92.8%, observed against infection with Delta, to -6.0% (95% CI: 29.2% to 12.7%) and 62.7% (95% CI: 35.7% to 77.9%), observed against infection with Omicron, for complete primary vaccination and booster dose, respectively. Conclusion: Consistent reduction in vaccine-induced protection against infection with Omicron was observed. Complete primary vaccination may not be protective against SARS-CoV-2 infection in regions where Omicron variant is dominant.The acquisition of sequencing equipment and reagents used in this study by the Instituto Nacional de Saúde Doutor Ricardo Jorge was partially funded by the HERA project (grant no. 2021/PHF/23776), supported by the European Commission through the European Centre for Disease Control, and also partially funded by the Genome PT project (grant no. POCI-01-0145-FEDER-022184), supported by COMPETE 2020–Operational Programme for Competitiveness and Internationalisation, Lisboa Portugal Regional Operational Programme, Algarve Portugal Regional Operational, under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund, and by the Portuguese Science and Technology Foundation. The Algarve Biomedical Center Laboratory received public funding through the Project ALG-D2-2021-06 Variants Screen in Southern Portugal–Monitoring Variants of Concern in Southern Portugal and the Portuguese Science and Technology Foundation national support through the Comprehensive Health Research Center (grant no. UIDP/04923/2020).info:eu-repo/semantics/publishedVersio

Mycoplasma pneumoniae causing nervous system lesion and SIADH in the absence of pneumonia

A patient was admitted for fever and acute respiratory failure (ARF), rapidly progressive tetraparesis, delirium, behavioral abnormalities, and diplopia. Leukocytosis and a rise in C-reactive protein were present. A syndrome of inappropriate anti-diuretic hormone secretion (SIADH) was also diagnosed. Lumbar puncture yielded colorless CFS with mononuclear pleocytosis and protein rise. Electrodiagnosis revealed demyelinating polyneuropathy and axonal degeneration. Serum IgG and IgM for mycoplasma pneumoniae (MP) was consistent with acute infection, and erythromycin was started with rapid resolution of symptoms. Contrarily to most reports, an associated respiratory disease was not present and SIADH in association with MP has been reported only once, in a patient without direct central nervous system (CNS) involvement. Differential diagnosis and possible pathogenic mechanisms are discussed

Endocardite das válvulas das cavidades direitas: a importância da ecocardiografia na identificação da(s) estrutura(s) afectada(s)

A endocardite das válvulas das cavidades direitas do coração é rara. Ocorre geralmente em doentes com toxicofilia endovenosa, portadores de pacemaker (PMD), portadores de próteses valvulares ou cateter venoso central e ainda em doentes com cardiopatias congénitas. A Ecocardiografia constitui o gold standard na identificação da(s) estrutura(s) afetada (s) e permite a orientação terapêutica. Apesar de ser rara, a endocardite das cavidades direitas deve ser tida em conta durante a realização de ecocardiografia transtorácica e/ou transesofágica que vise o diagnóstico de endocardite. A profilaxia antibiótica deve ser sempre aplicada antes da realização de qualquer procedimento invasivo de acordo com as recomendações publicadas. Acentua-se a necessidade de educar a população, prevenindo-se assim complicações graves resultantes de procedimentos simples cada vez mais vulgares nas populações mais jovens, como a colocação de piercing. Os autores apresentam dois casos clínicos dessa patologia

Wegener Granulomatosis

A granulomatose de Wegener corresponde a uma vasculite sistémica com atingimento das artérias de pequeno e médio calibre, em particular das vias aéreas superiores e inferiores e do rim, incluindo-se no diagnóstico diferencial das síndromas pulmão-rim. Os AA apresentam o caso clínico de uma senhora de 59 anos, internada na Unidade de Cuidados Intensivos Polivalente (UCIP) do Hospital Fernando da Fonseca com um quadro de insuficiência respiratória, hemoptises e insuficiência renal. Descreve-se o estudo etiológico desta situação, concluindo tratar-se de um caso de granulomatose de Wegener. A propósito deste caso são discutidos aspectos relevantes do diagnóstico, terapêutica e seguimento destes doentes

Mechanisms of leukocyte lipid body formation and function in inflammation

An area of increasingly interest for the understanding of cell signaling are the spatio-temporal aspects of the different enzymes involved in lipid mediator generation (eicosanoid-forming enzymes, phospholipases and their regulatory kinases and phosphatases) and pools of lipid precursors. The compartmentalization of signaling components within discrete and dynamic sites in the cell is critical for specificity and efficiency of enzymatic reactions of phosphorilation, enzyme activation and function. We hypothesized that lipid bodies - inducible non-membrane bound cytoplasmic lipid domains - function as specialized intracellular sites of compartmentalization of signaling with major roles in lipid mediator formation within leukocytes engaged in inflammatory process. Over the past years substantial progresses have been made demonstrating that all enzymes involved in eicosanoid synthesis localize at lipid bodies and lipid bodies are distinct sites for eicosanoid generation. Here we will review our current knowledge on the mechanisms of formation and functions of lipid bodies pertinent to inflammation

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT