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Background Knee osteoarthritis (KOA) is increasingly more prevalent and significant number of patients require knee arthroplasty. Although knee arthroplasty is generally successful, it takes months to recover physical function. Preoperative physical function is known to predict postoperative outcomes and exercise can improve preoperative physical function. However, patients with KOA have difficulty exercise on land due to pain and stiffness, while water exercise can be better tolerated. We hypothesized that preoperative water exercise to improve preoperative physical function will improve postoperative outcomes after total knee arthroplasty (TKA). Methods We enrolled 43 participants who were scheduled for elective TKA in 4–8 weeks and scored at or below 50th percentile in mobility assessment tool-sf (MAT-sf). All enrolled participants were assessed on 1) clinical osteoarthritis symptom severity using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 2) physical function using Short Physical Performance Battery (SPPB), 3) self-reported mobility using Mobility Assessment Tool-short form (MAT-sf), 4) depression using Geriatric Depression Scale-short form (GDS-sf), 5) cognitive function using Montreal Cognitive Assessment (MoCA). Blood samples for high-sensitivity-C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were stored at − 80 °C then all samples were analyzed together. All the enrolled participants were randomly assigned to the aquatic exercise intervention (AEI) or usual care group. Sixty minute sessions of AEI was conducted three times a week for 4–8 weeks. Participants in both groups were evaluated within 1 week before their scheduled surgery, as well as 4 weeks after the surgery. Results The mean age was 67.1 (±6.2), 44% were female, 74% were White. There is no statistically significant difference in combined outcome of any complication, unscheduled ER visit, and disposition to nursing home or rehab facility by AEI. However, AEI was associated with more favorable outcomes: WOMAC scores ( p  < 0.01), chair-stand ( p  = 0.019), MAT-sf as well as improved depression ( p  = 0.043) and cognition ( p  = 0.008). Conclusion 4–8 weeks of aquatic exercise intervention resulted in improved functional outcomes as well as improved depression and cognition in elderly patients undergoing TKA. A larger study is warranted to explore the role of water exercise in clinical and functional outcomes of TKA.

Obesity is associated with adverse changes in brain structure and function, in part, through crosstalk between adipose tissue (AT) and the brain. AT releases small extracellular vesicles (sEV) that can cross the blood–brain barrier (BBB) and modulate multiple pathophysiological pathways, including BBB function; however, this has never been investigated. We characterized circulating adipose tissue‐derived sEV (sEVAT) in adults with overweight and obesity and examined their effects on the BBB. The impact of adiposity and weight loss on these outcomes was also examined. sEVAT were isolated from the plasma of 29 adults (79% male; 93% White; mean age 66.2 ± 7.0 years; mean body mass index 36.0 ± 6.8 kg/m2) randomized to cardiac rehabilitation (CR) alone or CR plus a behavioural weight loss intervention (CR+WL). Following characterization of sEVAT size, concentration and total protein content, we assessed their effect on BBB permeability using an in vitro model. hCMEC/D3 cells were treated with sEVAT, and transendothelial electrical resistance (TEER) was measured at 0, 24, 48 and 72 h. Our findings show that sEVAT treatment decreased TEER by 40%, with a significantly lower TEER at 72 h compared with controls (23.138 ± 1.209 vs. 28.724 ± 1.613 Ω cm2, p = 0.012). TEER was also lower in participants with higher body mass index and body fat. However, we found no difference in TEER between the CR and CR+WL groups and no significant intervention effects on sEVAT characteristics or TEER. In conclusion, higher plasma sEVAT concentrations in adults with overweight and obesity are associated with greater adiposity, which might contribute to reductions in BBB function. What is the central question of this study? Small extracellular vesicles secreted from adipose tissue (sEVAT) might impair blood–brain barrier function. We developed an in vitro model to assess the effect of sEVAT on the blood–brain barrier in adults with overweight and obesity randomized to one of two lifestyle interventions. What is the main finding and its importance? Treatment of hCMEC/D3 cells with sEVAT decreased transendothelial resistance in both groups, with no significant intervention‐related effects. Higher plasma sEVAT concentrations were associated with greater adiposity, suggesting that sEVAT might contribute to the adverse effects of obesity on brain health.

Weight management is highly recommended to patients with diabetes mellitus. However, this prescription is often characterized by weight fluctuations. It remains unclear the effects of weight fluctuations on outcomes in diabetes mellitus. We used the public use dataset from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to assess the effects of baseline weight, change in weight, and body weight variability (BWV) on outcomes. The ACCORD trial participant's weights were documented annually during the trial. Our primary predictor variables were baseline weight, change in body weight (Initial – final) and BWV defined as average successive variability in weight (average absolute difference between successive values) during the trial. Cox proportional hazards model was used. Out of the 10,251 ACCORD participants, 911(8.9%), 2985(29.1%), and 6355(62%) were normal weight, overweight, and obese. After a mean of 3.5 years of follow-up, 10.2% had the primary outcome (nonfatal MI or nonfatal stroke or CV death), 4.3% had heart failure, 7% died, and 60.7% reported a microvascular complication. BWV was associated with the primary outcome, heart failure, death, and microvascular events in our full models which included BMI [HR (95%CI): 1.25(1.15 to 1.36), 1.59(1.45 to 1.75), 1.74(1.63 to 1.85) and 1.18(1.13 to 1.22), p < 0.0001 respectively). Participants who died were in the quartile that gained the most weight. In this post hoc analysis of ACCORD trial, body weight variability was significantly associated with poor outcomes independent of CVD risk factors and BMI. Our study is consistent with significant risk associated with weight fluctuations in patients with diabetes mellitus.

Understanding the minimal dose of physical activity required to achieve improvement in physical functioning and reductions in disability risk is necessary to inform public health recommendations. To examine the effect of physical activity dose on changes in physical functioning and the onset of major mobility disability in The Lifestyle Interventions and Independence for Elders (LIFE) Study. We conducted a multicenter single masked randomized controlled trial that enrolled participants in 2010 and 2011 and followed them for an average of 2.6 years. 1,635 sedentary men and women aged 70-89 years who had functional limitations were randomized to a structured moderate intensity walking, resistance, and flexibility physical activity program or a health education program. Physical activity dose was assessed by 7-day accelerometry and self-report at baseline and 24 months. Outcomes included the 400 m walk gait speed, the Short Physical Performance Battery (SPPB), assessed at baseline, 6, 12, and 24 months, and onset of major mobility disability (objectively defined by loss of ability to walk 400 m in 15 min). When the physical activity arm or the entire sample were stratified by change in physical activity from baseline to 24 months, there was a dose-dependent increase in the change in gait speed and SPPB from baseline at 6, 12, and 24 months. In addition, the magnitude of change in physical activity over 24 months was related to the reduction in the onset of major mobility disability (overall P < 0.001) (highest versus the lowest quartile of physical activity change HR 0.23 ((95% CI:0.10-0.52) P = 0.001) in the physical activity arm. We observed a dose-dependent effect of objectively monitored physical activity on physical functioning and onset of major mobility disability. Relatively small increases (> 48 minutes per week) in regular physical activity participation had significant and clinically meaningful effects on these outcomes. ClinicalsTrials.gov NCT00116194.

Background Pancreatic cancer is a disease of older adults, who may present with limited physiologic reserve. The authors hypothesized that a frailty index can predict postoperative outcomes after pancreaticoduodenectomy (PD). Methods All patients who underwent PD were identified in the 2005–2012 NSQIP Participant Use File. Patients undergoing emergency procedures, those with an American Society of Anesthesiologists (ASA) classification of five, and those with a diagnosis of preoperative sepsis were excluded from the study. A modified frailty index (mFI) was defined by 11 variables within the National Surgical Quality Improvement Program (NSQIP) previously used for the Canadian Study of Health and Aging-Frailty Index. An mFI score of 0.27 or higher was defined as a high mFI. Uni- and multivariate analyses were performed to evaluate postoperative outcomes. Results This study enrolled 9986 patients (age 65 ± 12 years, 48.8% female) who underwent PD. Of these patients, 6.4% ( n  = 637) had a high mFI (>0.27). Increasing mFI was associated with higher prevalence of postoperative morbidity ( p  < 0.001) and 30-days mortality ( p  < 0.001). In the univariate analysis, high mFI was associated with increased morbidity (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.43–1.97; p  < 0.001) and 30-days mortality (OR 2.45; 95% CI 1.74–3.45; p  < 0.001). After adjustment for age, sex, ASA classification, albumin level, and body mass index (BMI), high mFI remained an independent preoperative predictor of postoperative morbidity (OR 1.544; 95% CI 1.289–1.850; p  < 0.0001) and 30-days mortality (OR 1.536; 95% CI 1.049–2.248; p  = 0.027). Conclusions High mFI is associated with postoperative morbidity and mortality after PD and can aid in preoperative risk stratification.

PurposeAccording to the World Health Organization (WHO), 34.7% of females in the United States are obese (BMI ≥ 30) in 2014, compared to 32.5% in 2010. The previous research has demonstrated high BMI as an independent risk factor for surgical complications after breast surgery. As more patients become obese, we sought to examine whether increasing obesity had an effect on outcomes of women who underwent a unilateral mastectomy without breast reconstruction.MethodsThe study reviewed the 2007–2012 ACS-NSQIP database and identified all patients who underwent a unilateral mastectomy without reconstruction. Patients were then categorized and compared according to the World Health Organization obesity classification. Data were analyzed for minor complications (e.g., UTI and SSI) and major complications (e.g., renal failure, sepsis, deep vein thrombosis, return to operating room [RTOR], and cardiac arrest).ResultsA total of 7207 women were identified. Median BMI was 27.3 kg/m2. From the cohort, 453 patients (6.29%) had a major complication and 173 patients (2.40%) had a minor complication. 53 (0.74%) had bleeding complications, 148 (2.05%) had a surgical site infection (SSI), 352 (4.88%) RTOR, and 7 (0.01%) died within 30 days. Major complications (p = 0.005) and minor complications (p < 0.001) significantly increased as BMI increased. SSI and RTOR had increasing trends, but were not statistically significant.ConclusionsThis study characterizes the risk of complications in women undergoing unilateral mastectomies and shows that increasing obesity is associated with major and minor postoperative complications. Our finding highlights the need for personalized preoperative risk assessment and counseling of obese patients.

Background Incidence rates of cardiovascular disease (CVD) are increasing, partly driven by the diabetes epidemic. Novel prediction tools and modifiable treatment targets are needed to enhance risk assessment and management. Plasma metabolite associations with subclinical atherosclerosis were investigated in the Diabetes Heart Study (DHS), a cohort enriched for type 2 diabetes (T2D). Methods The analysis included 700 DHS participants, 438 African Americans (AAs), and 262 European Americans (EAs), in whom coronary artery calcium (CAC) was assessed using ECG-gated computed tomography. Plasma metabolomics using liquid chromatography-mass spectrometry identified 853 known metabolites. An ancestry-specific marginal model incorporating generalized estimating equations examined associations between metabolites and CAC (log-transformed (CAC + 1) as outcome measure). Models were adjusted for age, sex, BMI, diabetes duration, date of plasma collection, time between plasma collection and CT exam, low-density lipoprotein cholesterol (LDL-C), and statin use. Results At an FDR-corrected p-value < 0.05, 33 metabolites were associated with CAC in AAs and 36 in EAs. The androgenic steroids, fatty acid, phosphatidylcholine, and bile acid metabolism subpathways were associated with CAC in AAs, whereas fatty acid, lysoplasmalogen, and branched-chain amino acid (BCAA) subpathways were associated with CAC in EAs. Conclusions Strikingly different metabolic signatures were associated with subclinical coronary atherosclerosis in AA and EA DHS participants.

Background Whether physical activity can reduce cognitive frailty—a relatively new “compound” phenotype proposed in 2013—and whether the effect of physical activity differs based on levels of inflammation are unknown. Therefore, this study aimed to evaluate the effect of physical activity on cognitive frailty and whether baseline interleukin-6 (IL-6) levels modified this effect. Methods We used data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a multicenter, single-blinded randomized trial conducted at eight US field centers between February 2010 and December 2013. The main outcome was cognitive frailty at 24 months, expressed as an ordinal variable based on the six combinations of its two components: frailty (non-frail, pre-frail, and frail) and mild cognitive impairment (yes, no). Frailty and cognition were assessed by the Study of Osteoporotic Fractures (SOF) index and the Modified Mini-Mental State Examination (3MSE) scale, respectively. Plasma IL-6 was measured at baseline. Of the 1635 original randomized sedentary participants (70–89 years), this study included 1298 participants with data on both cognitive frailty and IL-6 assessments at baseline. Results After adjusting for field center, sex, and baseline levels of cognitive frailty, the ordinal logistic regression model revealed that participants in the physical activity group had 21% lower odds (odds ratio, 0.79; 95% confidence interval, 0.64–0.98) of worsening cognitive frailty over 24 months than those in the health education group. The effect of physical activity on cognitive frailty did not differ according to baseline IL-6 levels ( P for interaction = 0.919). The results did not change after additional adjustment for IL-6 subgroups and the inverse probability of remaining in the study. Comparable results were observed according to age, sex, ethnicity/race, and short physical performance battery score ( P for interaction = 0.835, 0.536, 0.934, and 0.458, respectively). Conclusions A 24-month structured, moderate-intensity physical activity program reduced cognitive frailty compared with a health education program in sedentary older persons, and this beneficial effect did not differ according to baseline levels of inflammatory biomarker IL-6. These findings suggest that the new cognitive frailty construct is modifiable and highlight the potential of targeting cognitive frailty for promoting healthy aging. Trial registration Clinicaltrials.gov, NCT01072500

Abstract Background Intracranial hypertension (ICH) is often presumptively diagnosed based on clinical or imaging findings. Clinical or imaging surrogates of ICH are not usually validated with reference standard direct intracranial pressure (dICP) recordings. Hypotheses Dogs with brain magnetic resonance imaging (MRI) or clinical features of presumed ICH would have higher dICP than dogs lacking those features. Animals Twenty dogs with gliomas and 3 normal controls. Methods Prospective, convenience study. Dogs were presumptively categorized with normal ICP or ICH from scores generated from described clinical and brain MRI indicators of ICH. dICP was recorded in anesthetized dogs using an intraparenchymal microsensor and compared between groups. Results dICP was not different between control (10.4 ± 2.1 mm Hg) and dogs with glioma (15.6 ± 8.3 mm Hg), or between dogs in clinically predicted ICP groups. Compared with dogs with MRI-predicted normal ICP, MRI-predicted ICH dogs had higher dICP (10.3 ± 4.1 versus 19.2 ± 7.9 mm Hg, P = .004), larger tumors (1.45 ± 1.2 versus 5.71 ± 3.03 cm3, P = .0004), larger optic nerve sheath diameters, and 14/14 (100%) displayed structural anatomical shifts on MRI. At a dICP threshold of 15 mm Hg, the sensitivity of MRI for predicting ICH was 90% and the specificity 69%. Conclusions and Clinical Relevance dICP measurements are feasible in dogs with brain tumors. MRI features including brain herniations, mass effect, and optic nerve size aid in the identification of dogs with ICH. Clinical estimation of ICP did not discriminate between dogs with and without ICH.

Crystallinity and crystal orientation have a predominant impact on a materials’ semiconducting properties, thus it is essential to manipulate the microstructure arrangements for desired semiconducting device performance. Here, ultra‐uniform hole‐transporting material (HTM) by self‐assembling COOH‐functionalized P3HT (P3HT‐COOH) is fabricated, on which near single crystal quality perovskite thin film can be grown. In particular, the self‐assembly approach facilitates the P3HT‐COOH molecules to form an ordered and homogeneous monolayer on top of the indium tin oxide (ITO) electrode facilitate the perovskite crystalline film growth with high quality and preferred orientations. After detailed spectroscopy and device characterizations, it is found that the carboxylic acid anchoring groups can down‐shift the work function and passivate the ITO surface, retarding the interface carrier recombination. As a result, the device made with the self‐assembled HTM show high open‐circuit voltage over 1.10 V and extend the lifetime over 4,300 h when storing at 30% relative humidity. Moreover, the cell works efficiently under much reduced light power, making it useful as power source under dim‐light conditions. The demonstration suggests a new facile way of fabricating monolayer HTM for high efficiency perovskite devices, as well as the interconnecting layer needed for tandem cell. Self‐assembled P3HT‐COOH is an excellent hole extraction layer to fabricate robust, high‐performance, and extremely reproducible perovskite solar cells. The well‐aligned self‐assembled P3HT‐COOH generates a dipole layer between indium tin oxide and perovskite, substantially retarding interface charge recombination and producing highly sensitive devices to dim light. The enhanced crystallinity and preferred out‐of‐plane orientation play a key role to suppress the device degradation process.