Bilateral bronchoalveolar lavage cytology profiles in a warmblood horse population during a 1-year period.

BACKGROUND: Bronchoalveolar lavage (BAL) cytology results from 1 lung might not be representative of both lungs. OBJECTIVES: To determine whether the lung site sampled would influence the horse's BAL cytology profile, and if a pooled BAL sample would be superior with regard to BAL cytology diagnosis in a cohort of healthy and subclinical asthmatic warmblood horses. ANIMALS: Fifty-nine horses in 2021 and 70 horses in 2022, the follow-up included 53 of the same in each year. METHODS: A cross-sectional study with follow-up included BAL cytology samples from individual lungs and from pooled BAL samples. The BAL samples were enumerated and differential cell count were applied to categorize the horses as control or with airway inflammation (AI). RESULTS: Bronchoalveolar lavage mast cell count was higher in left lung compared to right lung (2021; median 1.6 [range, 0.6-3.3] vs 1.2 [0.7-1.5] P = .009, 2022; median 3.1 [2.1-4.2] vs 2.4 [1.7-3.4], P < .001) and compared to pooled samples (2022; median 2.6 [1.7-3.7], P < .001). Between year 2021 and 2022, 17 of the horses had changes in BAL cytology from control to AI or vice versa. CONCLUSIONS AND CLINICAL IMPORTANCE: Pooled BAL sample was the least reliable for detecting AI, and was not representative of the overall lung condition.

Effectiveness of multidisciplinary nutritional support in older hospitalised patients: A systematic review and meta-analyses.

Malnutrition is common in older hospitalised patients. As the aetiology is multifactorial, nutritional care should involve a multidisciplinary team. However, the knowledge of the effectiveness of this strategy is limited. This systematic review aims at investigating the effectiveness of multidisciplinary nutritional support on mortality, readmissions and quality of life (QoL) in patients aged 65 years and above during hospitalisation and after discharge compared to usual practise. We conducted a series of systematic literature search from 2013 to 2017, with additional studies hand-searched from reference lists of retrieved publications. Eligible studies were controlled trials with a multidisciplinary nutritional intervention during hospitalisation and after discharge in older (65+) patients. A intervention by more than one profession incorporating a nutritional component was defined as "Multidisciplinary". The nutritional intervention included use of oral nutritional supplements (ONS), improved nutritional care, and/or dietary counselling. For quality assessment of studies, "Cochrane Collaboration's tool for assessing risk of bias" was used. Conduction of meta-analyses were by combining data from homogenous trials. The search resulted in five studies fulfilling the inclusion criteria, but varied in quality and type of interventions used. 598 patients were included. Meta-analyses found improved QoL (MD 0.13 (0.02, 0.23), P = 0.01) and indicated tendencies towards lower mortality (OR 0.50 (0.22, 1.14), P = 0.10), in the intervention group vs. control group. Meta-analysis showed no difference between intervention and control group regarding readmissions during intervention (OR 1.04 (0.40, 2.70)) or at a 26 weeks follow-up (OR 0.84 (0.18, 3.82)) Although a small number of studies and a relatively small sample size, a suggestion is that provision of multidisciplinary nutritional support may have a positive effect on mortality and improves quality of life in older patients. There is a need for more high-quality studies including multidisciplinary nutritional support to verify these findings. Study registration in PROSPERO is no. CRD42016047997.

Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro.

AIMS: To test the hypothesis that brown adipose tissue (BAT) is a metformin target tissue by investigating in vivo uptake of [11 C]-metformin tracer in mice and studying in vitro effects of metformin on cultured human brown adipocytes. MATERIALS AND METHODS: Tissue-specific uptake of metformin was assessed in mice by PET/CT imaging after injection of [11 C]-metformin. Human brown adipose tissue was obtained from elective neck surgery and metformin transporter expression levels in human and murine BAT were determined by qPCR. Oxygen consumption in metformin-treated human brown adipocyte cell models was assessed by Seahorse XF technology. RESULTS: Injected [11 C]-metformin showed avid uptake in the murine interscapular BAT depot. Metformin exposure in BAT was similar to hepatic exposure. Non-specific inhibition of the organic cation transporter (OCT) protein by cimetidine administration eliminated BAT exposure to metformin, demonstrating OCT-mediated uptake. Gene expression profiles of OCTs in BAT revealed ample OCT3 expression in both human and mouse BAT. Incubation of a human brown adipocyte cell models with metformin reduced cellular oxygen consumption in a dose-dependent manner. CONCLUSION: These results support BAT as a putative metformin target.

Characterization of immortalized human brown and white pre-adipocyte cell models from a single donor.

Brown adipose tissue with its constituent brown adipocytes is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. The molecular control of brown adipocyte differentiation and function has been extensively studied in mice, but relatively little is known about such regulatory mechanisms in humans, which in part is due to lack of human brown adipose tissue derived cell models. Here, we used retrovirus-mediated overexpression to stably integrate human telomerase reverse transcriptase (TERT) into stromal-vascular cell fractions from deep and superficial human neck adipose tissue biopsies from the same donor. The brown and white pre-adipocyte cell models (TERT-hBA and TERT-hWA, respectively) displayed a stable proliferation rate and differentiation until at least passage 20. Mature TERT-hBA adipocytes expressed higher levels of thermogenic marker genes and displayed a higher maximal respiratory capacity than mature TERT-hWA adipocytes. TERT-hBA adipocytes were UCP1-positive and responded to ß-adrenergic stimulation by activating the PKA-MKK3/6-p38 MAPK signaling module and increasing thermogenic gene expression and oxygen consumption. Mature TERT-hWA adipocytes underwent efficient rosiglitazone-induced 'browning', as demonstrated by strongly increased expression of UCP1 and other brown adipocyte-enriched genes. In summary, the TERT-hBA and TERT-hWA cell models represent useful tools to obtain a better understanding of the molecular control of human brown and white adipocyte differentiation and function as well as of browning of human white adipocytes.