Adaptive immune cells shape obesity-associated type 2 diabetes mellitus and less prominent comorbidities.

Obesity and type 2 diabetes mellitus (T2DM) are increasing in prevalence owing to decreases in physical activity levels and a shift to diets that include addictive and/or high-calorie foods. These changes are associated with the adoption of modern lifestyles and the presence of an obesogenic environment, which have resulted in alterations to metabolism, adaptive immunity and endocrine regulation. The size and quality of adipose tissue depots in obesity, including the adipose tissue immune compartment, are critical determinants of overall health. In obesity, chronic low-grade inflammation can occur in adipose tissue that can progress to systemic inflammation; this inflammation contributes to the development of insulin resistance, T2DM and other comorbidities. An improved understanding of adaptive immune cell dysregulation that occurs during obesity and its associated metabolic comorbidities, with an appreciation of sex differences, will be critical for repurposing or developing immunomodulatory therapies to treat obesity and/or T2DM-associated inflammation. This Review critically discusses how activation and metabolic reprogramming of lymphocytes, that is, T cells and B cells, triggers the onset, development and progression of obesity and T2DM. We also consider the role of immunity in under-appreciated comorbidities of obesity and/or T2DM, such as oral cavity inflammation, neuroinflammation in Alzheimer disease and gut microbiome dysbiosis. Finally, we discuss previous clinical trials of anti-inflammatory medications in T2DM and consider the path forward.

Commentary on Camell et al., Aging Induces Nlrp3 Inflammasome Dependent Adipose B Cell Expansion to Impair Metabolic Homeostasis.

The burden of aging and obesity is urging extended investigation into the molecular mechanisms that underlie chronic adipose tissue inflammation. B cell-targeted therapies are emerging as novel tools to modulate the immune system and thereby mitigate aging and obesity-related metabolic complications.

Hydrogen sulfide biosynthesis is impaired in the osteoarthritic joint.

Osteoarthritis (OA) is the most common form of arthritis and it is a leading cause of disability in the elderly. Its complete etiology is not known although there are several metabolic, genetic, epigenetic, and local contributing factors involved. At the moment, there is no cure for this pathology and treatment alternatives to retard or stop its progression are intensively being sought. Hydrogen sulfide (H2S) is a small gaseous molecule and is present in sulfurous mineral waters as its active component. Data from recent clinical trials shows that balneotherapy (immersion in mineral and/or thermal waters from natural springs) in sulfurous waters can improve OA symptoms, in particular, pain and function. Yet, the underlying mechanisms are poorly known. Hydrogen sulfide is also considered, with NO and CO, an endogenous signaling gasotransmitter. It is synthesized endogenously with the help of three enzymes, cystathionine gamma-lyase (CTH), cystathionine beta-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST). Here, the expression of these three enzymes was demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR) and their protein abundance [by immunohistochemistry and Western blot (WB)] in human articular cartilage. No significant differences were found in CBS or CTH expression or abundance, but mRNA and protein levels of 3-MPST were significantly reduced in cartilage form OA donors. Also, the biosynthesis of H2S from OA cartilage, measured with a specific microelectrode, was significantly lower than in OA-free tissue. Yet, no differences were found in H2S concentration in serum from OA patients and OA-free donors. The current results suggest that reduced levels of the mitochondrial enzyme 3-MPST in OA cartilage might be, at least in part, responsible for a reduction in H2S biosynthesis in this tissue and that impaired H2S biosynthesis in the joint might be a contributing factor to OA. This could contribute to explain why exogenous supplementation of H2S, for instance with sulfurous thermal water, has positive effects in OA patients.

Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro.

BACKGROUND: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. OBJECTIVES: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. METHODS: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1ß (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1ß (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. RESULTS: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1ß and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. CONCLUSION: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

Platelet-rich plasma in osteoarthritis treatment: review of current evidence.

Platelet-rich plasma (PRP) is defined as a volume of plasma with a platelet concentration higher than the average in peripheral blood. Many basic, preclinical and even clinical case studies and trials report PRP's ability to improve musculoskeletal conditions including osteoarthritis, but paradoxically, just as many conclude it has no effect. The purpose of this narrative review is to discuss the available relevant evidence that supports the clinical use of PRP in osteoarthritis, highlighting those variables we perceive as critical. Here, recent systematic reviews and meta-analyses were used to identify the latest randomized controlled trials (RCTs) testing a PRP product as an intra-articular treatment for knee osteoarthritis, compared with an intra-articular control (mostly hyaluronic acid). Conclusions in the identified RCTs are examined and compared. In total, five recent meta-analyses and systematic reviews were found meeting the above criteria. A total of 19 individual trials were identified in the five reviews but only 9 were level of evidence I RCTs, and many had moderate or high risks of bias. At present, results from these RCTs seem to favor PRP use over other intra-articular treatments to improve pain scales in the short and medium term (6-12 months), but the overall level of evidence is low. As a result, clinical effectiveness of PRP for knee osteoarthritis treatment is still under debate. This is, prominently, the result of a lack of standardization of PRP products, scarceness of high quality RCTs not showing high risks of bias, and poor patient stratification for inclusion in the RCTs.

Ventilatory weaning practices in intensive care units in the city of Cali.

OBJECTIVE: Early weaning from mechanical ventilation is one of the primary goals in managing critically ill patients. There are various techniques and measurement parameters for such weaning. The objective of this study was to describe the practices of ventilatory weaning in adult intensive care units in the city of Cali. METHODS: A survey of 32 questions (some multiple choice) evaluating weaning practices was distributed to physiotherapists and respiratory therapists working in intensive care units, to be answered anonymously. RESULTS: The most common strategy for the parameter set was the combination of continuous positive airway pressure with pressure support (78%), with a large variability in pressure levels, the most common range being 6 to 8 cm H2O. The most common weaning parameters were as follows: tidal volume (92.6%), respiratory rate (93.3%) and oxygen saturation (90.4%). The most common waiting time for registration of the parameters was >15 minutes (40%). The measurements were preferably obtained from the ventilator display. CONCLUSION: The methods and measurement parameters of ventilatory weaning vary greatly. The most commonly used method was continuous positive airway pressure with more pressure support and the most commonly used weaning parameters were the measured tidal volume and respiratory rate.

Prácticas de destete ventilatorio en las unidades de cuidado intensivo de la ciudad de Cali / Ventilatory weaning practices in intensive care units in the city of Cali

Objetivo: El destete temprano de la ventilación mecánica es uno de los objetivos primordiales en el manejo del paciente crítico. Existen diversas técnicas y parámetros de medida para realizarlo. El objetivo de esta investigación fue describir las prácticas del destete ventilatorio en unidades de cuidado intensivo adulto en la ciudad de Cali. Métodos: Una encuesta de 32 preguntas; algunas de múltiple escogencia, que evaluaron las prácticas del destete, fue distribuida entre los fisioterapeutas y terapeutas respiratorios que trabajaban en unidades de cuidado intensivo, para ser respondida de forma anónima. Resultados: La estrategia más frecuente para el registro de parámetros fue la combinación de presión positiva continua con presión de soporte (78%), con gran variabilidad en los niveles de presión, siendo el rango más frecuente de 6 a 8cmH2O. Los parámetros de destete más registrados fueron: el volumen corriente (92,6%), la frecuencia respiratoria (93,3%) y la saturación de oxígeno (90,4%). El tiempo de espera más frecuente para el registro de los parámetros fue >15 minutos (40%). Las medidas se realizaron preferentemente con el display del ventilador. Conclusion: Existe una gran variabilidad sobre los métodos y la medición de los parámetros de destete ventilatorio. El método más utilizado fue presión positiva continua en la vía aérea más presión de soporte y los parámetros de destete más usados fueron la medición del volumen corriente y la frecuencia respiratoria. .

Objective: Early weaning from mechanical ventilation is one of the primary goals in managing critically ill patients. There are various techniques and measurement parameters for such weaning. The objective of this study was to describe the practices of ventilatory weaning in adult intensive care units in the city of Cali. Methods: A survey of 32 questions (some multiple choice) evaluating weaning practices was distributed to physiotherapists and respiratory therapists working in intensive care units, to be answered anonymously. Results: The most common strategy for the parameter set was the combination of continuous positive airway pressure with pressure support (78%), with a large variability in pressure levels, the most common range being 6 to 8cmH2O. The most common weaning parameters were as follows: tidal volume (92.6%), respiratory rate (93.3%) and oxygen saturation (90.4%). The most common waiting time for registration of the parameters was >15 minutes (40%). The measurements were preferably obtained from the ventilator display. Conclusion: The methods and measurement parameters of ventilatory weaning vary greatly. The most commonly used method was continuous positive airway pressure with more pressure support and the most commonly used weaning parameters were the measured tidal volume and respiratory rate. .

Massilia umbonata sp. nov., able to accumulate poly-ß-hydroxybutyrate, isolated from a sewage sludge compost-soil microcosm.

A bacterial strain, designated strain LP01(T), was isolated from a laboratory-scale microcosm packed with a mixture of soil and sewage sludge compost designed to study the evolution of microbial biodiversity over time. The bacterial strain was selected for its potential ability to store polyhydroxyalkanoates (PHAs) as intracellular granules. The cells were aerobic, Gram-stain-negative, non-endospore-forming motile rods. Phylogenetically, the strain was classified within the genus Massilia, as its 16S rRNA gene sequence had similarity of 99.2 % with respect to those of Massilia albidiflava DSM 17472(T) and M. lutea DSM 17473(T). DNA-DNA hybridization showed low relatedness of strain LP01(T) to the type strains of other, phylogenetically related species of the genus Massilia. It contained Q-8 as the predominant ubiquinone and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH) as the major fatty acid(s). It was found to contain small amounts of the fatty acids C18 : 0 and C14 : 0 2-OH, a feature that served to distinguish it from its closest phylogenetic relatives within the genus Massilia. The DNA G+C content was 66.0 mol%. Phylogenetic, phenotypic and chemotaxonomic data obtained in this study suggest that strain LP01(T) represents a novel species of the genus Massilia, for which the name Massilia umbonata sp. nov. is proposed. The type strain is LP01(T) ( = CECT 7753(T) = DSM 26121(T)).