Chronic pain in people living with dementia: challenges to recognising and managing pain, and personalising intervention by phenotype.

Pain is common in people with dementia, and pain can exacerbate the behavioural and psychological symptoms of dementia. Effective pain management is challenging, not least in people with dementia. Impairments of cognition, communication and abstract thought can make communicating pain unreliable or impossible. It is unclear which biopsychosocial interventions for pain management are effective in people with dementia, and which interventions for behavioural and psychological symptoms of dementia are effective in people with pain. The result is that drugs, physical therapies and psychological therapies might be either underused or overused. People with dementia and pain could be helped by assessment processes that characterise an individual's pain experience and dementia behaviours in a mechanistic manner, phenotyping. Chronic pain management has moved from a 'one size fits all' approach, towards personalised medicine, where interventions recommended for an individual depend upon the key mechanisms underlying their pain, and the relative values they place on benefits and adverse effects. Mechanistic phenotyping through careful personalised evaluation would define the mechanisms driving pain and dementia behaviours in an individual, enabling the formulation of a personalised intervention strategy. Central pain processing mechanisms are particularly likely to be important in people with pain and dementia, and interventions to accommodate and address these may be particularly helpful, not only to relieve pain but also the symptoms of dementia.

Serum Vitamin D Levels, Disease Activity Score-28 for Rheumatoid Arthritis with C-Reactive Protein (DAS28-CRP), and Cardiac Remodeling Determined by Ventricular Dimensions and Left Atrium Diameter in Patients with Rheumatoid Arthritis: A Prospective Observational Study.

BACKGROUND Rheumatoid arthritis (RA) can cause extra-articular manifestations, and the myocardium can be a target. This study aimed to describe structural and functional cardiac echocardiographic variables in RA patients and to evaluate whether vitamin D (VD) levels and inflammation markers, evaluated by Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS28-CRP), are associated with cardiac remodeling (CR) in this population. MATERIAL AND METHODS This prospective observational study evaluated 90 patients with RA in Botucatu University Hospital wards from 2014 to 2017. Clinical data were recorded, including demographic information, comorbidities, length of disease, and treatment type. Serum VD and C-reactive protein levels were measured, and the DAS28-CRP was calculated. A transthoracic echocardiography study was performed. The outcome evaluated was CR. This parameter was assessed by left ventricular geometric patterns and left atrium diameter. RESULTS We evaluated 90 RA patients. The mean age was 52.9±10.8 years, and 17.8% were male. The length of the disease was 96 (60-180) months. Serum VD levels were 30.7±10.4 ng/mL and the DAS28 was 2.7±0.9. Regarding the CR parameters, 56.7% had altered left ventricular geometric patterns and 25.8% had enlargement of left atrium diameter. Even in multivariate analysis, the left ventricular geometric patterns were not associated with the VD levels and the inflammation marker used. However, sufficient VD levels protect from left atrium enlargement (OR: 0.905; IC 95%: 0.843-0.973; P=0.007). CONCLUSIONS Low serum vitamin D values, but not inflammation, are associated with CR in patients with RA.

The Role of Extracellular Matrix in the Experimental Acute Aortic Regurgitation Model in Rats.

BACKGROUND: Mechanisms involved in cardiac remodelling by aortic regurgitation (AR) and the moment when cardiac dysfunction begins are largely unknown. This study aimed to investigate cardiac morphology and function after 1, 4, 8, and 12 weeks of experimental AR in Wistar rats. Extracellular matrix was also investigated as the potential mechanism that underlies the AR remodelling process. METHODS: Male Wistar rats underwent surgical acute AR (AR group, n=51) or a sham surgery (sham group, n=32). After the procedure, serial transthoracic echocardiograms were performed at 1, 4, 8, and 12 weeks. Morphometry of cardiac tissue and the activities of metalloproteinase 2 (MMP-2) and tissue metalloproteinase inhibitor-1 (TIMP-1) were analysed. Statistical analysis was performed by two-way ANOVA. Significance level was 5%. RESULTS: The AR group presented an increase in the sphericity index (week 1); an increase in the left atrium, left ventricular mass index, TIMP-1 and MMP-2 activities, and collagen fraction (week 4); an increase in myocyte area (week 8); and a reduction in fraction shortening (week 12). First, the chamber became more spherical; second, MMP-2 and TIMP-1 were activated and this may have contributed to hypertrophy and atrial enlargement, until systolic dysfunction occurred. CONCLUSIONS: This study showed a sequence of abnormalities that preceded myocardial dysfunction in an experimental model of AR. First, haemodynamic volume overload led to a more spherical left ventricle chamber. Second, MMP-2 and TIMP-1 transitorily increased and may have contributed to atrial enlargement, eccentric hypertrophy, and systolic dysfunction.

Association Between Serum Myostatin Levels, Hospital Mortality, and Muscle Mass and Strength Following ST-Elevation Myocardial Infarction.

AIM: This study aimed to evaluate the association between serum myostatin levels, hospital mortality, and muscle mass and strength following ST-segment elevation myocardial infarction (STEMI). METHODS: This was a prospective observational study. Within 48 hours of admission, bioelectrical impedance and handgrip strength were assessed and blood samples collected for myostatin evaluation. Hospital mortality was recorded. A multiple logistic regression model was also constructed, adjusted by parameters that exhibited significant differences in the univariate analysis, to evaluate the association between myostatin levels and hospital mortality. RESULTS: One hundred and two (102) patients were included: mean age was 60.5±10.6 years, 67.6% were male, and 6.9% died during hospital stay. Univariate analysis showed that patients with lower myostatin levels had higher mortality rates. Serum myostatin levels positively correlated with handgrip strength (r=0.355; p<0.001) and appendicular skeletal muscle mass index (r=0.268; p=0.007). Receiver operating characteristic (ROC) curve analysis revealed that lower myostatin levels were associated with hospital mortality at the <2.20 ng/mL cut-off. Multiple logistic regression showed that higher serum myostatin levels were associated with reduced hospital mortality when adjusted by ß blocker use (OR, 0.228; 95% CI, 0.054-0.974; p=0.046). CONCLUSIONS: Serum myostatin concentrations positively correlated with muscle mass and strength in STEMI patients. Further assessment of serum myostatin association with mortality should be conducted using a larger sample and assessing the additive value to the Global Registry of Acute Coronary Events (GRACE) or thrombolysis in myocardial infarction (TIMI) risk scores.

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction.

BACKGROUND/AIMS: The objective of our study was to evaluate the effects of zinc supplementation on cardiac remodeling following acute myocardial infarction in rats. METHODS: Animals were subdivided into 4 groups and observed for 3 months: 1) Sham Control; 2) Sham Zinc: Sham animals receiving zinc supplementation; 3) Infarction Control; 4) Infarction Zinc. After the followup period, we studied hypertrophy and ventricular geometry, functional alterations in vivo and in vitro, changes related to collagen, oxidative stress, and inflammation, assessed by echocardiogram, isolated heart study, western blot, flow cytometer, morphometry, and spectrophotometry. RESULTS: Infarction induced a significant worsening of the functional variables. On the other hand, zinc attenuated both systolic and diastolic cardiac dysfunction induced by infarction. Considering the infarct size, there was no difference between the groups. Catalase and superoxide dismutase decreased in infarcted animals, and zinc increased its activity. We found higher expression of collagens I and III in infarcted animals, but there was no effect of zinc supplementation. Likewise, infarcted animals had higher levels of IL-10, but without zinc interference. Nrf-2 values were not different among the groups. Infarction increased the amount of Treg cells in the spleen as well as the amount of total lymphocytes. Zinc increased the amount of CD4+ in infarcted animals, but we did not observe effects in relation to Treg cells. CONCLUSION: zinc attenuates cardiac remodeling after infarction in rats; this effect is associated with modulation of antioxidant enzymes, but without the involvement of collagens I and III, Nrf-2, IL-10, and Treg cells.

Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats.

BACKGROUND/AIMS: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. METHODS AND RESULTS: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-ß, PI3K, AKT, NFκB, S6K, and ERK. CONCLUSION: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.

Pamidronate attenuates diastolic dysfunction induced by myocardial infarction associated with changes in geometric patterning.

BACKGROUND/AIMS: The aim of this study was to evaluate the influence of pamidronate on ventricular remodeling after myocardial infarction. METHODS: Male Wistar rats were assigned to four groups: a sham group, in which animals were submitted to simulated surgery and received weekly subcutaneous injection of saline (S group; n=14); a group in which animals received weekly subcutaneous injection of pamidronate (3 mg/kg of body weight) and were submitted to simulated surgery (SP group, n=14); a myocardial infarction group, in which animals were submitted to coronary artery ligation and received weekly subcutaneous injection of saline (MI group, n=13); and a myocardial infarction group with pamidronate treatment (MIP group, n=14). The rats were observed for three months. RESULTS: Animals submitted to MI had left chamber enlargement and worse diastolic and systolic function compared with SHAM groups. E/A ratio, LV posterior and relative wall thickness were lower in the MIP compared with the MI group. There was no interaction between pamidronate administration and MI on systolic function, myocyte hypertrophy, collagen content, and calcium handling proteins. CONCLUSION: Pamidronate attenuates diastolic dysfunction following MI.

Identifying and Managing Frailty: A Survey of UK Healthcare Professionals.

Frailty is a common condition that leads to multiple adverse outcomes. Frailty should be identified and managed in a holistic, evidence-based and patient-centered way. We aimed to understand how UK healthcare professionals (HCPs) identify and manage frailty in comparison with UK Fit for Frailty guidelines, their frailty training, their confidence in providing support and organizational pathways for this. An online mixed-methods survey was distributed to UK HCPs supporting older people through professional bodies, special interest groups, key contacts, and social media. From 137 responses, HCPs valued frailty assessment but used a mixture of tools that varied by profession. HCPs felt confident managing frailty and referred older people to a wide range of supportive services, but acknowledged a lack of formalized training opportunities, systems, and pathways for frailty management. Clearer pathways, more training, and stronger interprofessional communication, appropriate to each setting, may further support HCPs in frailty management.

Mini Nutritional Assessment predicts gait status and mortality 6 months after hip fracture.

The aim of the present study was to evaluate the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening (NRS) 2002 and the American Society of Anesthesiologists Physical Status Score (ASA) as predictors of gait status and mortality 6 months after hip fracture. A total of eighty-eight consecutive patients over the age of 65 years with hip fracture admitted to an orthopaedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, and the MNA, the NRS 2002 and the ASA were performed. Gait status and mortality were evaluated 6 months after hip fracture. Of the total patients, two were excluded because of pathological fractures. The remaining eighty-six patients (aged 80·2 (sd 7·3) years) were studied. Among these patients 76·7 % were female, 69·8 % walked with or without support and 12·8 % died 6 months after the fracture. In a multivariate analysis, only the MNA was associated with gait status 6 months after hip fracture (OR 0·773, 95 % CI 0·663, 0·901; P= 0·001). In the Cox regression model, only the MNA was associated with mortality 6 months after hip fracture (hazard ratio 0·869, 95 % CI 0·757, 0·998; P= 0·04). In conclusion, the MNA best predicts gait status and mortality 6 months after hip fracture. These results suggest that the MNA should be included in the clinical stratification of patients with hip fracture to identify and treat malnutrition in order to improve the outcomes.

Effects of Pera Orange Juice and Moro Orange Juice in Healthy Rats: A Metabolomic Approach.

Cardiovascular disease is a leading cause of death worldwide. Heart failure is a cardiovascular disease with high prevalence, morbidity, and mortality. Several natural compounds have been studied for attenuating pathological cardiac remodeling. Orange juice has been associated with cardiovascular disease prevention by attenuating oxidative stress. However, most studies have evaluated isolated phytochemicals rather than whole orange juice and usually under pathological conditions. In this study, we evaluated plasma metabolomics in healthy rats receiving Pera or Moro orange juice to identify possible metabolic pathways and their effects on the heart. METHODS: Sixty male Wistar rats were allocated into 3 groups: control (C), Pera orange juice (PO), and Moro orange juice (MO). PO and MO groups received Pera orange juice or Moro orange juice, respectively, and C received water with maltodextrin (100 g/L). Echocardiogram and euthanasia were performed after 4 weeks. Plasma metabolomic analysis was performed by high-resolution mass spectrometry. Type I collagen was evaluated in picrosirius red-stained slides and matrix metalloproteinase (MMP)-2 activity by zymography. MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-4, type I collagen, and TNF-α protein expression were evaluated by Western blotting. RESULTS: We differentially identified three metabolites in PO (N-docosahexaenoyl-phenylalanine, diglyceride, and phosphatidylethanolamine) and six in MO (N-formylmaleamic acid, N2-acetyl-L-ornithine, casegravol isovalerate, abscisic alcohol 11-glucoside, cyclic phosphatidic acid, and torvoside C), compared to controls, which are recognized for their possible roles in cardiac remodeling, such as extracellular matrix regulation, inflammation, oxidative stress, and membrane integrity. Cardiac function, collagen level, MMP-2 activity, and MMP-9, TIMP-2, TIMP-4, type I collagen, and TNF-α protein expression did not differ between groups. CONCLUSION: Ingestion of Pera and Moro orange juice induces changes in plasma metabolites related to the regulation of extracellular matrix, inflammation, oxidative stress, and membrane integrity in healthy rats. Moro orange juice induces a larger number of differentially expressed metabolites than Pera orange juice. Alterations in plasma metabolomics induced by both orange juice are not associated with modifications in cardiac extracellular matrix components. Our results allow us to postulate that orange juice may have beneficial effects on pathological cardiac remodeling.

Acute green tea intake attenuates circulating microRNA expression induced by a high-fat, high-saturated meal in obese women: A randomized crossover study.

The objective of this study was to assess whether acute green tea (GT) supplementation attenuates inflammatory and oxidative stress biomarkers induced by high-fat, high-saturated (HFHS) meals in obese women, and to assess its ability to modulate circulating microRNA (miRNA) expression. This was a randomized, double-blind, crossover study. The study included obese women over 18 years old who had no comorbidities. In the first moment, patients were instructed to take 2 capsules of placebo or GT (738 mg) at 10:00 p.m. and to fast overnight. The next morning, a blood sample was collected, and an HFHS meal was offered to the patients. Another blood sample was collected 5 hours after the meal. In the second moment, patients who received placebo in the first moment now received the GT and vice-versa. Serum inflammatory and oxidative stress biomarkers were measured, and circulating levels of miRNA were evaluated. Fifteen women with mean age of 35.5±9.9 years were included in the final analysis. There was no difference regarding inflammatory and oxidative stress biomarkers. However, patients who consumed GT had lower circulating expression of 62 miRNAs compared with patients who did not consume GT. Predictive analysis of target genes showed 1,757 targets regulated by the 62 miRNAs. Notably, 5 miRNAs (miR-1297, miR-192-5p, miR-373-3p, miR-595 and miR-1266-5p) regulate genes associated with TGF-beta, CARM1, RSK, and BMP pathways. Our study showed that GT inhibited the expression of miRNAs induced by HFHS meal intake. These results shed light on the mechanisms involved in the beneficial effects of GT ingestion.

Aldosterone is not involved in the ventricular remodeling process induced by tobacco smoke exposure.

BACKGROUND/AIMS: Renin-angiotensin-aldosterone system blockade with a mineralocorticoid-receptor antagonist has not yet been studied in exposure to tobacco smoke (TS) models. Thus, this study investigated the role of spironolactone on cardiac remodeling induced by exposure to tobacco smoke. METHODS: Male Wistar rats were divided into 4 groups: a control group (group C, n=11); a group with 2 months of cigarette smoke exposure (group TS-C, n=13); a group that received spironolactone 20 mg/kg of diet/day and no cigarette smoke exposure (group TS-S, n=13); and a group with 2 months of cigarette smoke exposure and spironolactone supplementation (group S, n=12). The rats were observed for a period of 60 days, during which morphological, biochemical and functional analyses were performed. RESULTS: There was no difference in invasive mean arterial pressure among the groups. There were no interactions between tobacco smoke exposure and spironolactone in the morphological and functional analysis. However, in the echocardiographic analysis, the TS groups had left chamber enlargement, higher left ventricular mass index and higher isovolumetric relaxation time corrected by heart rate compared with the non-TS groups. In vitro left ventricular diastolic function also worsened in the TS groups and was not influenced by spironolactone. In addition, there were no differences in myocardial levels of IFN-γ, TNF-α, IL-10, ICAM-1 and GLUT4 [TS: OR 0.52, 95%CI (-0.007; 0.11); Spironolactone: OR -0.01, 95%CI (-0.07;0.05)]. CONCLUSION: Our data do not support the participation of aldosterone in the ventricular remodeling process induced by exposed to cigarette smoke.

Early echocardiographic predictors of increased left ventricular end-diastolic pressure three months after myocardial infarction in rats.

BACKGROUND: The objective of this study was to determine the early echocardiographic predictors of elevated left ventricular end-diastolic pressure (LVEDP) after a long follow-up period in the infarcted rat model. MATERIAL/METHODS: Five days and three months after surgery, sham and infarcted animals were subjected to transthoracic echocardiography. Regression analysis and receiver-operating characteristic (ROC) curve were performed for predicting increased LVEDP 3 months after MI. RESULTS: Among all of the variables, assessed 5 days after myocardial infarction, infarct size (OR: 0.760; CI 95% 0.563-0.900; p=0.005), end-systolic area (ESA) (OR: 0.761; CI 95% 0.564-0.900; p=0.008), fractional area change (FAC) (OR: 0.771; CI 95% 0.574-0.907; p=0.003), and posterior wall-shortening velocity (PWSV) (OR: 0.703; CI 95% 0.502-0.860; p=0.048) were predictors of increased LVEDP. The LVEDP was 3.6±1.8 mmHg in the control group and 9.4±7.8 mmHg among the infarcted animals (p=0.007). Considering the critical value of predictor variables in inducing cardiac dysfunction, the cut-off value was 35% for infarct size, 0.33 cm2 for ESA, 40% for FAC, and 26 mm/s for PWSV. CONCLUSIONS: Infarct size, FAC, ESA, and PWSV, assessed five days after myocardial infarction, can be used to estimate an increased LVEDP three months following the coronary occlusion.

Prevalence and predictors of ventricular remodeling after anterior myocardial infarction in the era of modern medical therapy.

BACKGROUND: The consequences of aggressive therapy following a myocardial infarction (MI) on ventricular remodeling are not well established. Thus, the objective of this study was to analyze the prevalence, clinical characteristics, and predictors of left ventricular remodeling in the era of modern medical therapy. MATERIAL/METHODS: Clinical characteristics and echocardiographic data were analyzed in 66 consecutive patients with anterior infarction at admission and at 6-month follow-up. Ventricular remodeling was defined as an increase of 10% in ventricular end-systolic or end-diastolic diameter. RESULTS: In our study, 58% of patients presented with ventricular remodeling. Patients with remodeling possessed higher total plasma creatine kinase (CPK), MB-fraction (CPK-MB), heart rate, heart failure, shortness of breath, and reperfusion therapy than patients without remodeling. In contrast, patients with remodeling had a smaller ejection fraction, E-Wave deceleration time (EDT), and early (E' Wave) and late (A' Wave) diastolic mitral annulus velocity (average of septal and lateral walls), but a higher E/E' than patients without remodeling. Patients with remodeling used more diuretics, digoxin, oral anticoagulants and aldosterone antagonists than patients without remodeling. In the multivariate analyses, only E' Wave was an independent predictor of ventricular remodeling. Each 1 unit increase in the E' Wave was associated with a 59% increased odds of ventricular remodeling. CONCLUSIONS: In patients with anterior MI, despite contemporary treatment, ventricular remodeling is still a common event. In addition, diastolic function can have an important role as a predictor of remodeling in this scenario.

Influence of taurine on cardiac remodeling induced by tobacco smoke exposure.

BACKGROUND/AIMS: To investigate the effect of taurine on cardiac remodeling induced by smoking. METHODS: In the first step, rats were allocated into two groups: Group C (n = 14): control; Group T (n = 14): treated with taurine (3% in drinking water), for three months. In the second step, rats were allocated into two groups: Group ETS (n = 9): rats exposed to tobacco smoke; Group ETS-T (n = 9): rats exposed to tobacco smoke and treated with taurine for two months. RESULTS: After three months, taurine presented no effects on morphological or functional variables of normal rats assessed by echocardiogram. On the other hand, after two months, ETS-T group presented higher LV wall thickness (ETS = 1.30 (1.20-1.42); ETS-T = 1.50 (1.40-1.50); p = 0.029), E/A ratio (ETS = 1.13 ± 0.13; ETS-T = 1.37 ± 0.26; p = 0.028), and isovolumetric relaxation time normalized for heart rate (ETS = 53.9 ± 4.33; ETS-T = 72.5 ± 12.0; p < 0.001). The cardiac activity of the lactate dehydrogenase was higher in the ETS-T group (ETS = 204 ± 14 nmol/mg protein; ETS-T = 232 ± 12 nmol/mg protein; p < 0.001). ETS-T group presented lower levels of phospholamban (ETS = 1.00 ± 0.13; ETS-T = 0.82 ± 0.06; p = 0.026), phosphorylated phospholamban at Ser16 (ETS = 1.00 ± 0.14;ETS-T = 0.63 ± 0.10;p = 0.003), and phosphorylated phosfolamban/phospholamban ratio (ETS = 1.01 ± 0.17; ETS-T = 0.77 ± 0.11; p = 0.050). CONCLUSION: In normal rats, taurine produces no effects on cardiac morphological or functional variables. On the other hand, in rats exposed to cigarette smoke, taurine supplementation increases wall thickness and worsens diastolic function, associated with alterations in calcium handling protein and cardiac energy metabolism.

Tobacco smoke induces ventricular remodeling associated with an increase in NADPH oxidase activity.

BACKGROUND: Recent studies have assessed the direct effects of smoking on cardiac remodeling and function. However, the mechanisms of these alterations remain unknown. The aim of this study was to investigate de role of cardiac NADPH oxidase and antioxidant enzyme system on ventricular remodeling induced by tobacco smoke. METHODS: Male Wistar rats that weighed 200-230 g were divided into a control group (C) and an experimental group that was exposed to tobacco smoke for a period of two months (ETS). After the two-month exposure period, morphological, biochemical and functional analyses were performed. RESULTS: The myocyte cross-sectional area and left ventricle end-diastolic dimension was increased 16.2% and 33.7%, respectively, in the ETS group. The interstitial collagen volume fraction was also higher in ETS group compared to the controls. In addition to these morphological changes, the ejection fraction and fractional shortening were decreased in the ETS group. Importantly, these alterations were related to augmented heart oxidative stress, which was characterized by an increase in NADPH oxidase activity, increased levels of lipid hydroperoxide and depletion of antioxidant enzymes (e.g., catalase, superoxide dismutase and glutathione peroxidase). In addition, cardiac levels of IFN-γ, TNF-α and IL-10 were not different between the groups. CONCLUSION: Cardiac alterations that are induced by smoking are associated with increased NADPH oxidase activity, suggesting that this pathway plays a role in the ventricular remodeling induced by exposure to tobacco smoke.

Retinoic acid prevents ventricular remodelling induced by tobacco smoke exposure in rats.

OBJECTIVE: Our objective was to test the hypothesis that retinoic acid supplementation could attenuate ventricular remodelling induced by tobacco smoke exposure in rats. METHODS AND RESULTS: Wistar rats were allocated into three groups: control (C, n = 8); exposed to tobacco smoke (ETS, n = 9); exposed to tobacco smoke and all-trans-retinoic acid (ETS-RA, n = 9). After two months, cardiac function and geometry were assessed by echocardiography, and geometry changes were confirmed by morphometric analysis. Data are expressed as mean +/- SD or medians (including the lower quartile and upper quartile). ETS showed higher normalized left ventricular diastolic diameters than groups C and ETS-RA (C = 18.4 +/- 3.57 mm/kg, ETS = 23.0 +/- 1.8, ETS-RA = 19.5 +/- 0.99; P <0.05) and systolic diameters (C = 8.25 +/- 2.16 mm/kg, ETS = 11.5 +/- 1.31, ETS-RA = 8.25 +/- 0.71 mm/kg; P < 0.05). ETS showed reduced ejection fraction (C= 91 +/- 2.0, ETS = 87 +/- 3.0, ETS-RA = 92 +/- 3.0; P < 0.05) and fractional shortening (C = 55.8 +/- 4.41%, ETS = 49.7 +/- 4.43%, ETS-RA = 57.6 +/- 5.15 %; P= 0.01) compared to C and ETS-RA. ETS had increased myocyte cross-sectional area (C = 294 +/- 21 mm2, ETS = 352 +/-44, ETS-RA = 310 +/- 35; P < 0.05) compared to C and ETS-RA. Considering all variables, there were no differences between groups C and ETS-RA. CONCLUSION: Retinoic acid prevented ventricular remodelling induced by tobacco smoke exposure.

Overcoming protein-energy malnutrition in older adults in the residential care setting: A narrative review of causes and interventions.

Malnutrition, in particular protein-energy malnutrition, is a highly prevalent condition in older adults, and is associated with low muscle mass and function, and increased prevalence of physical frailty. Malnutrition is often exacerbated in the residential care setting due to factors including lack of dentition and appetite, and increased prevalence of dementia and dysphagia. This review aims to provide an overview of the available literature in older adults in the residential care setting regarding the following: links between sarcopenia, frailty, and malnutrition (in particular, protein-energy malnutrition (PEM)), recognition and diagnosis of malnutrition, factors contributing to PEM, and the effectiveness of different forms of protein supplementation (in particular, oral nutritional supplementation (ONS) and protein-fortified foods (PFF)) to target PEM. This review found a lack of consensus on effective malnutrition diagnostic tools and lack of universal requirement for malnutrition screening in the residential care setting, making identifying and treating malnutrition in this population a challenge. When assessing the use of protein supplementation in the residential care setting, the two primary forms of supplementation were ONS and PFF. There is evidence that ONS and PFF increase protein and energy intakes in residential care setting, yet compliance with supplementation and their impact on functional status is unclear and conflicting. Further research comparing the use of ONS and PFF is needed to fully determine feasibility and efficacy of protein supplementation in the residential care setting.