Potentially Inadequate Real-Life Speech Levels by Healthcare Professionals during Communication with Older Inpatients.

BACKGROUND: The aim of this study was to investigate real-life speech levels of health professionals during communication with older inpatients in small group settings. METHODS: This is a prospective observational study assessing group interactions between geriatric inpatients and health professionals in a geriatric rehabilitation unit of a tertiary university hospital (Bern, Switzerland). We measured speech levels of health professionals during three typical group interactions (discharge planning meeting (n = 21), chair exercise group (n = 5), and memory training group (n = 5)) with older inpatients. Speech levels were measured using the CESVA LF010 (CESVA instruments s.l.u., Barcelona, Spain). A threshold of <60 dBA was defined as a potentially inadequate speech level. RESULTS: Overall, mean talk time of recorded sessions was 23.2 (standard deviation 8.3) minutes. The mean proportion of talk time with potentially inadequate speech levels was 61.6% (sd 32.0%). The mean proportion of talk time with potentially inadequate speech levels was significantly higher in chair exercise groups (95.1% (sd 4.6%)) compared to discharge planning meetings (54.8% (sd 32.5%), p = 0.01) and memory training groups (56.3% (sd 25.4%), p = 0.01). CONCLUSIONS: Our data show that real-life speech level differs between various types of group settings and suggest potentially inadequate speech levels by healthcare professionals requiring further study.

Three Cases of Alcohol-Induced Acute-On-Chronic Liver Failure With Successful Support by Adipose-Derived Stem Cells.

OBJECTIVES: Acute liver failure (ALF) and acute-on-chronic liver failure (AOCLF) are critical medical conditions with urgent therapy requirements. When ALF or AOCLF are due to alcohol intoxication or based on chronic alcohol abuse, virtually, no therapeutic options are available as liver transplantation is prohibited. In this case series, treatment of alcohol-induced ALF/AOCLF with adipose--derived stem cells (ASC) was tested under compassionate use. METHODS: ASC from 2 donors were isolated, cultured, and expanded by established protocols. ASC were administered to 3 individuals with either ALF or AOCLF due to alcohol abuse under compassionate use. Clinical presentation, serum measurements, and other diagnostic methods were compiled before ASC treatment and during the disease course after ASC administration. RESULTS: Three patients were admitted to the Department of Gastroenterology, Hepatology, and Infectious Diseases (University Hospital Magdeburg) with acute or AOCLF due to alcohol abuse. All 3 patients presented in impaired general condition and with elevated, in 1 case drastically elevated, serum liver enzyme concentrations. Treatment with ASC led to improvements in general condition and reduction of serum transaminases. In 2 cases, reduction of liver stiffness and increase of liver function by the C methacetin breath test were observed after ASC treatment. Recovery to a normal condition was achieved between 1 and 2 months after ASC treatment. No adverse effects associated to ASC treatment were observed. DISCUSSION: ASC treatment may be a feasible option to enhance recovery from alcohol-induced ALF or AOCLF. ASC treatment seems safe in the presented cases.

A short-term plastic adherence incubation of the stromal vascular fraction leads to a predictable GMP-compliant cell-product.

Introduction: Mesenchymal stromal/stem cells (MSCs) derived from fat tissue are an encouraging tool for regenerative medicine. They share properties similar to the bone marrow-derived MSCs, but the amount of MSCs per gram of fat tissue is 500x higher. The fat tissue can easily be digested by collagenase, releasing a heterogeneous cell fraction called stromal vascular fraction (SVF) which contains a variable amount of stromal/stem cells. In Europe, cell products like the SVF derived from fat tissue are considered advanced therapy medicinal product (ATMPs). As a consequence, the manufacturing process has to be approved via GMP-compliant process validation. The problem of the process validation for SVF is the heterogeneity of this fraction. Methods: Here, we modified existing purification strategies by adding an additional plastic adherence incubation of maximal 20 hours after SVF isolation. The resulting cell fraction was characterized and compared to SVF as well as cultivated adipose-derived stromal/stem cells (ASCs) with respect to viability and cell yield, the expression of surface markers, differentiation potential and cytokine expression. Results: Short-term incubation significantly reduced the heterogeneity of the resulting cell fraction compared to SVF. The cells were able to differentiate into adipocytes, chondrocytes, and osteoblasts. More importantly, they expressed trophic proteins which have been previously associated with the beneficial effects of MSCs. Furthermore, GMP compliance of the production process described herein was acknowledged by the national regulatory agencies (DE_BB_01_GMP_2017_1018). Conclusion: Addition of a short purification-step after the SVF isolation is a cheap and fast strategy to isolate a homogeneous uncultivated GMP-compliant cell fraction of ASCs.

Effects of health risk assessment and counselling on physical activity in older people: A pragmatic randomised trial.

BACKGROUND: Interventions to increase physical activity (PA) among older community-dwelling adults may be enhanced by using multidimensional health risk assessment (HRA) as a basis for PA counselling. METHODS: The study was conducted among nondisabled but mostly frail persons 65 years of age and older at an ambulatory geriatric clinic in Bucharest, Romania. From May to July 2014, 200 participants were randomly allocated to intervention and control groups. Intervention group participants completed an initial HRA questionnaire and then had monthly counselling sessions with a geriatrician over a period of six months that were aimed at increasing low or maintaining higher PA. Counselling also addressed the older persons' concomitant health risks and problems. The primary outcome was PA at six months (November 2014 to February 2015) evaluated with the International Physical Activity Questionnaire. RESULTS: At baseline, PA levels were similar in intervention and control groups (median 1089.0, and 1053.0 MET [metabolic equivalent of task] minutes per week, interquartile ranges 606.0-1401.7, and 544.5-1512.7 MET minutes per week, respectively). Persons in the intervention group had an average of 11.2 concomitant health problems and risks (e.g., pain, depressive mood, hypertension). At six months, PA increased in the intervention group by a median of 180.0 MET minutes per week (95% confidence interval (CI) 43.4-316.6, p = 0.01) to 1248.8 MET minutes per week. In the control group, PA decreased by a median of 346.5 MET minutes per week (95% CI 178.4-514.6, p<0.001) to 693.0 MET minutes per week due to a seasonal effect, resulting in a difference of 420.0 MET minutes per week (95% CI 212.7-627.3, p< 0.001) between groups. CONCLUSION: The use of HRA to inform individualized PA counselling is a promising method for achieving improvements in PA, and ultimately health and longevity among large groups of community-dwelling older persons. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number: ISRCTN11166046.

Effect of health risk assessment and counselling on health behaviour and survival in older people: a pragmatic randomised trial.

BACKGROUND: Potentially avoidable risk factors continue to cause unnecessary disability and premature death in older people. Health risk assessment (HRA), a method successfully used in working-age populations, is a promising method for cost-effective health promotion and preventive care in older individuals, but the long-term effects of this approach are unknown. The objective of this study was to evaluate the effects of an innovative approach to HRA and counselling in older individuals for health behaviours, preventive care, and long-term survival. METHODS AND FINDINGS: This study was a pragmatic, single-centre randomised controlled clinical trial in community-dwelling individuals aged 65 y or older registered with one of 19 primary care physician (PCP) practices in a mixed rural and urban area in Switzerland. From November 2000 to January 2002, 874 participants were randomly allocated to the intervention and 1,410 to usual care. The intervention consisted of HRA based on self-administered questionnaires and individualised computer-generated feedback reports, combined with nurse and PCP counselling over a 2-y period. Primary outcomes were health behaviours and preventive care use at 2 y and all-cause mortality at 8 y. At baseline, participants in the intervention group had a mean ± standard deviation of 6.9 ± 3.7 risk factors (including unfavourable health behaviours, health and functional impairments, and social risk factors) and 4.3 ± 1.8 deficits in recommended preventive care. At 2 y, favourable health behaviours and use of preventive care were more frequent in the intervention than in the control group (based on z-statistics from generalised estimating equation models). For example, 70% compared to 62% were physically active (odds ratio 1.43, 95% CI 1.16-1.77, p = 0.001), and 66% compared to 59% had influenza vaccinations in the past year (odds ratio 1.35, 95% CI 1.09-1.66, p = 0.005). At 8 y, based on an intention-to-treat analysis, the estimated proportion alive was 77.9% in the intervention and 72.8% in the control group, for an absolute mortality difference of 4.9% (95% CI 1.3%-8.5%, p = 0.009; based on z-test for risk difference). The hazard ratio of death comparing intervention with control was 0.79 (95% CI 0.66-0.94, p = 0.009; based on Wald test from Cox regression model), and the number needed to receive the intervention to prevent one death was 21 (95% CI 12-79). The main limitations of the study include the single-site study design, the use of a brief self-administered questionnaire for 2-y outcome data collection, the unavailability of other long-term outcome data (e.g., functional status, nursing home admissions), and the availability of long-term follow-up data on mortality for analysis only in 2014. CONCLUSIONS: This is the first trial to our knowledge demonstrating that a collaborative care model of HRA in community-dwelling older people not only results in better health behaviours and increased use of recommended preventive care interventions, but also improves survival. The intervention tested in our study may serve as a model of how to implement a relatively low-cost but effective programme of disease prevention and health promotion in older individuals. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number: ISRCTN 28458424.

Evaluation of a novel photography-based home assessment protocol for identification of environmental risk factors for falls in elderly persons.

PRINCIPLES: To evaluate the validity and feasibility of a novel photography-based home assessment (PhoHA) protocol, as a possible substitute for on-site home assessment (OsHA). METHODS: A total of 20 patients aged ≥65 years who were hospitalised in a rehabilitation centre for musculoskeletal disorders affecting mobility participated in this prospective validation study. For PhoHA, occupational therapists rated photographs and measurements of patients' homes provided by patients' confidants. For OsHA, occupational therapists conducted a conventional home visit. RESULTS: Information obtained by PhoHA was 79.1% complete (1,120 environmental factors identified by PhoHA vs 1416 by OsHA). Of the 1,120 factors, 749 had dichotomous (potential hazards) and 371 continuous scores (measurements with tape measure). Validity of PhoHA to potential hazards was good (sensitivity 78.9%, specificity 84.9%), except for two subdomains (pathways, slippery surfaces). Pearson's correlation coefficient for the validity of measurements was 0.87 (95% confidence interval [CI 0.80-0.92, p <0.001). Agreement between methods was 0.52 (95%CI 0.34-0.67, p <0.001, Cohen's kappa coefficient) for dichotomous and 0.86 (95%CI 0.79-0.91, p <0.001, intraclass correlation coefficient) for continuous scores. Costs of PhoHA were 53.0% lower than those of OsHA (p <0.001). CONCLUSIONS: PhoHA has good concurrent validity for environmental assessment if instructions for confidants are improved. PhoHA is potentially a cost-effective method for environmental assessment.

The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands.

Bitter taste is a basic taste modality, required to safeguard animals against consuming toxic substances. Bitter compounds are recognized by G-protein-coupled bitter taste receptors (TAS2Rs). The human TAS2R10 responds to the toxic strychnine and numerous other compounds. The mechanism underlying the development of the broad tuning of some TAS2Rs is not understood. Using comparative modeling, site-directed mutagenesis, and functional assays, we identified residues involved in agonist-induced activation of TAS2R10, and investigated the effects of different substitutions on the receptor's response profile. Most interestingly, mutations in S85(3.29) and Q175(5.40) have differential impact on stimulation with different agonists. The fact that single point mutations lead to improved responses for some agonists and to decreased activation by others indicates that the binding site has evolved to optimally accommodate multiple agonists at the expense of reduced potency. TAS2R10 shares the agonist strychnine with TAS2R46, another broadly tuned receptor. Engineering the key determinants for TAS2R46 activation by strychnine in TAS2R10 caused a loss of response to strychnine, indicating that these paralog receptors display different strychnine-binding modes, which suggests independent acquisition of agonist specificities. This implies that the gene duplication event preceding primate speciation was accompanied by independent evolution of the strychnine-binding sites.

Immunohistochemical detection of TAS2R38 protein in human taste cells.

The sense of taste plays an important role in the evaluation of the nutrient composition of consumed food. Bitter taste in particular is believed to serve a warning function against the ingestion of poisonous substances. In the past years enormous progress was made in the characterization of bitter taste receptors, including their gene expression patterns, pharmacological features and presumed physiological roles in gustatory as well as in non-gustatory tissues. However, due to a lack in TAS2R-specifc antibodies the localization of receptor proteins within gustatory tissues has never been analyzed. In the present study we have screened a panel of commercially available antisera raised against human bitter taste receptors by immunocytochemical experiments. One of these antisera was found to be highly specific for the human bitter taste receptor TAS2R38. We further demonstrate that this antibody is able to detect heterologously expressed TAS2R38 protein on Western blots. The antiserum is, however, not able to interfere significantly with TAS2R38 function in cell based calcium imaging analyses. Most importantly, we were able to demonstrate the presence of TAS2R38 protein in human gustatory papillae. Using double immunofluorescence we show that TAS2R38-positive cells form a subpopulation of PLCbeta2 expressing cells. On a subcellular level the localization of this bitter taste receptor is neither restricted to the cell surface nor particularly enriched at the level of the microvilli protruding into the pore region of the taste buds, but rather evenly distributed over the entire cell body.

Insights into the binding of Phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor.

Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models.

Modulation of bitter taste perception by a small molecule hTAS2R antagonist.

Human bitter taste is mediated by the hTAS2R family of G protein-coupled receptors. The discovery of the hTAS2Rs enables the potential to develop specific bitter receptor antagonists that could be beneficial as chemical probes to examine the role of bitter receptor function in gustatory and nongustatory tissues. In addition, they could have widespread utility in food and beverages fortified with vitamins, antioxidants, and other nutraceuticals, because many of these have unwanted bitter aftertastes. We employed a high-throughput screening approach to discover a novel bitter receptor antagonist (GIV3727) that inhibits activation of hTAS2R31 (formerly hTAS2R44) by saccharin and acesulfame K, two common artificial sweeteners. Pharmacological analyses revealed that GIV3727 likely acts as an orthosteric, insurmountable antagonist of hTAS2R31. Surprisingly, we also found that this compound could inhibit five additional hTAS2Rs, including the closely related receptor hTAS2R43. Molecular modeling and site-directed mutagenesis studies suggest that two residues in helix 7 are important for antagonist activity in hTAS2R31 and hTAS2R43. In human sensory trials, GIV3727 significantly reduced the bitterness associated with the two sulfonamide sweeteners, indicating that hTAS2R antagonists are active in vivo. Our results demonstrate that small molecule bitter receptor antagonists can effectively reduce the bitter taste qualities of foods, beverages, and pharmaceuticals.