[COMISA: co-morbid insomnia and sleep apnea].

Obstructive sleep apnea (OSA) is a frequent pathology with clinical implications. Its comorbidity with the complaint of insomnia is common, and has been increasingly studied in recent years, due to the multiple negative synergies highlighted by these two conditions, notably on all-cause excess mortality, cardiovascular risk, quality of life and sleep, as well as mental health. This comorbidity between insomnia and sleep apnea has recently been referred to as COMISA («co-morbid insomnia and sleep apnea»).

Deciphering Natural Killer Cell Cytotoxicity Against Medulloblastoma in vitro and in vivo: Implications for Immunotherapy.

Purpose: Medulloblastoma (MB) is the most prevalent paediatric brain tumour. Despite improvements in patient survival with current treatment strategies, the quality of life of these patients remains poor owing to the sequelae and relapse risk. An alternative, or, in addition to the current standard treatment, could be considered immunotherapy, such as Natural Killer cells (NK).

Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell-depleting agents.

Administration of plasma therapy may contribute to viral control and survival of COVID-19 patients receiving B-cell-depleting agents that impair humoral immunity. However, little is known on the impact of anti-CD20 pre-exposition on the kinetics of SARS-CoV-2-specific antibodies. Here, we evaluated the relationship between anti-spike immunoglobulin G (IgG) kinetics and the clinical status or intra-host viral evolution after plasma therapy in 36 eligible hospitalized COVID-19 patients, pre-exposed or not to B-cell-depleting treatments.

Characterization of an Innovative Biomaterial Derived From Human Wharton's Jelly as a New Promising Coating for Tissue Engineering Applications.

The extracellular matrix (ECM) offers the opportunity to create a biomaterial consisting of a microenvironment with interesting biological and biophysical properties for improving and regulating cell functions. Animal-derived ECM are the most widely used as an alternative to human tissues that are of very limited availability. However, incomplete decellularization of these tissues presents a high risk of immune rejection and disease transmission.

[The Internal medicine articles that struck us the most in 2021].

The year 2021 has seen many breakthroughs in general internal medicine, despite the ongoing COVID-19 pandemic, with multiple implications in our daily clinical practice. From shorter antibiotic treatment duration in community-acquired pneumonia, to new indications for colchicine treatment, without forgetting better targets of hemoglobin for transfusion, questioning of the interest of high dose vitamin D substitution when preventing falls in older patients and finally disappointing hopes for new indications of albumin substitution in cirrhosis, the literature is full of new evidence. Each year, the chief residents of the internal medicine ward in Lausanne university hospital (CHUV) in Switzerland meet up to share their readings: here is a selection of ten articles, chosen, summarized, and commented for you.

[Albumin substitution : A review of the indications in general internal medicine].

Albumin has multiple physiological functions such as maintenance of oncotic pressure, binding of plasmatic molecule, immunomodulation and endothelial stabilization. Considering potential negative effects of hypoalbuminemia, the question of albumin substitution arises. For cirrhotic patients, indications for substitution are well established with a scientific consensus for spontaneous bacterial peritonitis, paracentesis-induced circulatory dysfunction and hepatorenal syndrome.

Impact of GG on the Emulsion Stability of Raw Milk.

Lactic acid bacteria (LAB) have been studied for several decades to understand and determine their mechanism and interaction within the matrix into which they are introduced. This study aimed to determine the spatial distribution of GG (LGG) in a dairy matrix and to decipher its behaviour towards milk components, especially fat globules. Two strains of this widely studied bacterium with expected probiotic effects were used: LGG WT with pili on the cell surface and its pili-depleted mutant-LGG Δ-in order to determine the involvement of these filamentous proteins.

Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery.

In these times of COVID-19 pandemic, concern has been raised about the potential effects of SARS-CoV-2 infection on immunocompromised patients, particularly on those receiving B-cell depleting agents and having therefore a severely depressed humoral response. Convalescent plasma can be a therapeutic option for these patients. Understanding the underlying mechanisms of convalescent plasma is crucial to optimize such therapeutic approach.

[The Internal medicine articles that struck us the most in 2020].

2020 has continued to bring important progress in all areas of internal medicine, impacting our daily practice. From a shift to oral stepdown antibiotics in infectious endocarditis, to new indications for apixaban, SLGT-2 inhibitors and macrolide antibiotics, passing by the catheter-based renal denervation in hypertension, early paracentesis in cirrhosis and new diagnostic criteria in pulmonary embolism, internal medicine journals are full of novelties. Every year, the chief residents of internal medicine at the Swiss University Hospital of Lausanne meet up to share their readings: here is their selection of eleven articles, summarized and commented for you.

Adhesive Interactions Between Lactic Acid Bacteria and β-Lactoglobulin: Specificity and Impact on Bacterial Location in Whey Protein Isolate.

In the last decade, there has been an increasing interest in the potential health effects associated with the consumption of lactic acid bacteria (LAB) in foods. Some of these bacteria such as GG (LGG) are known to adhere to milk components, which may impact their distribution and protection within dairy matrices and therefore is likely to modulate the efficiency of their delivery. However, the adhesive behavior of most LAB, as well as its effect on food structuration and on the final bacterial distribution within the food matrix remain very poorly studied.

In vitro and in vivo evaluation of an electrospun-aligned microfibrous implant for Annulus fibrosus repair.

Annulus fibrosus (AF) impairment is associated with reherniation, discogenic pain, and disc degeneration after surgical partial discectomy. Due to a limited intrinsic healing capacity, defects in the AF persist over time and it is hence necessary to adopt an appropriate strategy to close and repair the damaged AF. In this study, a cell-free biodegradable scaffold made of polycaprolactone (PCL), electrospun, aligned microfibers exhibited high levels of cell colonization, alignment, and AF-like extracellular matrix deposition when evaluated in an explant culture model.

New tools for non-invasive exploration of collagen network in cartilaginous tissue-engineered substitute.

In tissue engineering approaches, the quality of substitutes is a key element to determine its ability to treat cartilage defects. However, in clinical practice, the evaluation of tissue-engineered cartilage substitute quality is not possible due to the invasiveness of the standard procedure, which is to date histology. The aim of this work was to validate a new innovative system performed from two-photon excitation laser adapted to an optical macroscope to evaluate at macroscopic scale the collagen network in cartilage tissue-engineered substitutes in confrontation with gold standard histologic techniques or immunohistochemistry to visualize type II collagen.

PAMAM G4.5-chlorin e6 dendrimeric nanoparticles for enhanced photodynamic effects.

There is currently great interest in the development of efficient and specific carrier delivery platforms for systemic photodynamic therapy. Therefore, we aimed to develop covalent conjugates between the photosensitizer chlorin e6 (Ce6) and PAMAM G4.5 dendrimers.

Live cell imaging reveals actin-cytoskeleton-induced self-association of the actin-bundling protein WLIM1.

Crosslinking of actin filaments into bundles is essential for the assembly and stabilization of specific cytoskeletal structures. However, relatively little is known about the molecular mechanisms underlying actin bundle formation. The two LIM-domain-containing proteins define a novel and evolutionarily conserved family of actin-bundling proteins whose actin-binding and -crosslinking activities primarily rely on their LIM domains.

Photodynamic therapy with conventional and PEGylated liposomal formulations of mTHPC (temoporfin): comparison of treatment efficacy and distribution characteristics in vivo.

A major challenge in the application of a nanoparticle-based drug delivery system for anticancer agents is the knowledge of the critical properties that influence their in vivo behavior and the therapeutic performance of the drug. The effect of a liposomal formulation, as an example of a widely-used delivery system, on all aspects of the drug delivery process, including the drug's behavior in blood and in the tumor, has to be considered when optimizing treatment with liposomal drugs, but that is rarely done. This article presents a comparison of conventional (Foslip®) and polyethylene glycosylated (Fospeg®) liposomal formulations of temoporfin (meta-tetra[hydroxyphenyl]chlorin) in tumor-grafted mice, with a set of comparison parameters not reported before in one model.

Chondrocalcin is internalized by chondrocytes and triggers cartilage destruction via an interleukin-1β-dependent pathway.

Chondrocalcin is among the most highly synthesized polypeptides in cartilage. This protein is released from its parent molecule, type II pro-collagen, after secretion by chondrocytes. A participation of extracellular, isolated chondrocalcin in mineralization was proposed more than 25 years ago, but never demonstrated.

Structural and mechanical multi-scale characterization of white New-Zealand rabbit Achilles tendon.

Multi-scale characterization of structures and mechanical behavior of biological tissues are of huge importance in order to evaluate the quality of a biological tissue and/or to provide bio-inspired scaffold for functional tissue engineering. Indeed, the more information on main biological tissue structures we get, the more relevant we will be to design new functional prostheses for regenerative medicine or to accurately evaluate tissues. From this perspective, we have investigated the structures and their mechanical properties from nanoscopic to macroscopic scale of fresh ex-vivo white New-Zealand rabbit Achilles tendon using second harmonic generation (SHG) microscopy, atomic force microscopy (AFM) and tensile tests to provide a "simple" model whose parameters are relevant of its micro or nano structure.

Osteogenic differentiation of human bone marrow mesenchymal stem cells in hydrogel containing nacre powder.

Nacre (or mother of pearl) can facilitate bone cell differentiation and can speed up their mineralization. Here we report on the capability of nacre to induce differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) and the production of extracellular matrix. hBM-MSCs were encapsulated in an alginate hydrogel containing different concentrations of powdered nacre and cultured in the same environment until Day 28.

Tumor vascular responses to antivascular and antiangiogenic strategies: looking for suitable models.

Antiangiogenic and vascular disrupting agents are in the current cancer therapeutic armamentarium. A better understanding of the intricate mechanisms ruling neovessel survival within tumors during or after treatment is needed. Refinement of imaging and a growing knowledge of molecular biology of tumor vascularization provide new insights.

Hemocompatibility and biofunctionality of two poly(2-(dimethylamino)ethyl methacrylate-co-poly(ethyleneglycol) copolymers.

To mask the antigenic sites of cells for cell therapies, especially for blood transfusion, we investigated the hemocompatibility of two poly(2-(dimethylamino)ethyl methacrylate-co-poly(ethyleneglycol) compared with that of the homopolymer without PEG. Our strategy relies on the potential ability of these copolymers to self-assemble at the erythrocyte surface. The cationic sequence of the copolymer should be able to interact with the glycocalyx by ionic interaction.

Simultaneous Gram and viability staining on activated sludge exposed to erythromycin: 3D CLSM time-lapse imaging of bacterial disintegration.

The effect of erythromycin on activated sludge bacteria according to their Gram type was investigated with 3-dimensional Confocal Laser Scanning Microscopy (CLSM) time-lapse imaging. The fluorescent stains SYTOX Green and Texas Red-X conjugate of wheat germ agglutinin stained dying bacteria and Gram(+) bacteria respectively. Time-lapse imaging allowed an understanding of the staining mechanism and the measurement of the death rate.

Collagenous extracellular matrix of cartilage submitted to mechanical forces studied by second harmonic generation microscopy.

Osteoarthritis is a degenerative pathology leading to degradation of the extracellular matrix (ECM). Similar effects can be visualized when applying mechanical or biochemical constraints on cartilaginous tissue. Here, we characterized modification of the ECM appearing under mechanical compression and/or biochemical action (hypoxia environment, nitric oxide and collagenase action).

Anchoring secreted proteins in endoplasmic reticulum by plant oleosin: the example of vitamin B12 cellular sequestration by transcobalamin.

Background: Oleosin is a plant protein localized to lipid droplets and endoplasmic reticulum of plant cells. Our idea was to use it to target functional secretory proteins of interest to the cytosolic side of the endoplasmic reticulum of mammalian cells, through expressing oleosin-containing chimeras. We have designed this approach to create cellular models deficient in vitamin B12 (cobalamin) because of the known problematics associated to the obtainment of effective vitamin B12 deficient cell models.

Correlation between in vivo pharmacokinetics, intratumoral distribution and photodynamic efficiency of liposomal mTHPC.

Foslip is a recently designed third generation photosensitiser based on unilamellar dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol (DPPC/DPPG) liposomal formulations of meta-tetra(hydroxyphenyl)chlorine (mTHPC). The present study investigates Foslip behaviour and its photodynamic efficiency in EMT6 xenografted nude mice at different times following i.v.