Physical Phenotype Research Articles

Quantifying bias in psychological and physical health in the UK Biobank imaging sub-sample.

UK Biobank is a prospective cohort study of around half-a-million general population participants, recruited between 2006 and 2010, with baseline studies at recruitment and multiple assessments since. From 2014 to date, magnetic resonance imaging (MRI) has been pursued in a participant sub-sample, with the aim to scan around n = 100k. This sub-sample is studied widely and therefore understanding its relative characteristics is important for future reports. We aimed to quantify psychological and physical health in the UK Biobank imaging sub-sample, compared with the rest of the cohort. We used t-tests and χ2 for continuous/categorical variables, respectively, to estimate average differences on a range of cognitive, mental and physical health phenotypes. We contrasted baseline values of participants who attended imaging (versus had not), and compared their values at the imaging visit versus baseline values of participants who were not scanned. We also tested the hypothesis that the associations of established risk factors with worse cognition would be underestimated in the (hypothesized) healthier imaging group compared with the full cohort. We tested these interactions using linear regression models. On a range of cognitive, mental health, cardiometabolic, inflammatory and neurological phenotypes, we found that 47 920 participants who were scanned by January 2021 showed consistent statistically significant ‘healthy’ bias compared with the ∼450 000 who were not scanned. These effect sizes were small to moderate based on Cohen’s d/Cramer’s V metrics (range = 0.02 to −0.21 for Townsend, the largest effect size). We found evidence of interaction, where stratified analysis demonstrated that associations of established cognitive risk factors were smaller in the imaging sub-sample compared with the full cohort. Of the ∼100 000 participants who ultimately will undergo MRI assessment within UK Biobank, the first ∼50 000 showed some ‘healthy’ bias on a range of metrics at baseline. Those differences largely remained at the subsequent (first) imaging visit, and we provide evidence that testing associations in the imaging sub-sample alone could lead to potential underestimation of exposure/outcome estimates.

Ability of 3 Frailty Measures to Predict Short-Term Outcomes in Older Patients Admitted for Post-Acute Inpatient Rehabilitation.

To evaluate the ability of 3 commonly used frailty measures to predict short-term clinical outcomes in older patients admitted for post-acute inpatient rehabilitation. Observational cohort study. Consecutive patients (n= 207) admitted to a geriatric inpatient rehabilitation facility. Frailty on admission was assessed using a frailty index, the physical frailty phenotype, and the Clinical Frailty Scale (CFS). Predictive capacity of the frailty instruments was analyzed for (1) nonhome discharge, (2) readmission to acute care, (3) functional decline, and (4) prolonged length of stay, using multivariate logistic regression models and receiver operating characteristic (ROC) curves. The number of patients classified as frail was 91 (44.0%) with the frailty index, 134 (64.7%) using the frailty phenotype, and 151 (73.0%) with the CFS. The 3 frailty measures revealed acceptable discriminatory accuracy for nonhome discharge (area under the curve ≥ 0.7) but differed in their predictive ability: the adjusted odds ratio (OR) for nonhome discharge was highest for the CFS [6.2, 95% confidence interval (CI) 1.8-21.1], compared to the frailty index (4.1, 95% CI 2.0-8.4) and the frailty phenotype (OR 2.9, 95% CI 1.2-6.6). For the other outcomes, discriminatory accuracy based on ROC tended to be lower and predictive ability varied according to frailty measure. Readmission to acute care from inpatient rehabilitation was predicted by all instruments, most pronounced by the frailty phenotype (OR 5.4, 95% CI 1.6-18.8) and the frailty index (OR 2.5, 95% CI 1.1-5.6), and less so by the CFS (OR 1.4, 95% CI 0.5-3.8). Frailty measures may contribute to improved prediction of outcomes in geriatric inpatient rehabilitation. The choice of the instrument may depend on the individual outcome of interest and the corresponding discriminatory ability of the frailty measure.

Mouse Strain Differences in Female Mice Fed a Short‐Term Western Diet

Mouse models of diet‐induced obesity are commonly used for studies of metabolic disease. Since sex and strain differences are suggested to influence the results, studies have been generally limited to males of one mouse strain. This limited study population may impact the understanding of the effect of sex and genetic background on metabolic parameters. Therefore, the purpose of this study was to examine potential differences in short‐term feeding of a high fat diet in two popular strains of female mice. Ten‐week‐old, female FVB/N (FVB, n=20) and C57BL/6‐Ncrl (C57, n=20) mice were fed a Western Diet (WD; 40% calories from fat) or standard chow diet (13% calories from fat) for 6 weeks. Body weight was measured at weekly intervals and the Open Field Test (OFT) was administered to assess changes in activity and behavior at baseline and 6 weeks. The OFT consists of a circular arena, where mice were observed for 10 minutes using a video tracking software system to determine distance, speed, and motion. Tissues and blood were harvested after the 6‐week feeding period. Body weights and organ masses (i.e., heart, liver, adipose, and spleen) were significantly greater in FVB‐chow compared to C57‐chow mice. After 6‐weeks of feeding, body weights, adipose mass, and liver mass were significantly higher in FVB‐WD but not in C57‐WD compared to respective chow groups. FVB‐WD had reduced heart weight to tibial length ratios (FVB‐WD: 6.05±0.14 vs. FVB‐chow: 5.41±0.14, P<0.05) and higher serum ketone body levels compared to FVB‐chow (FVB‐WD: 0.42±0.03 vs. FVB‐chow: 0.76±0.15 mM, P<0.05), changes that were not observed in C57‐WD. OFT results revealed significant effects of diet and mouse strain. At baseline, FVB mice spent greater time moving (422± vs. 379±11 sec, P<0.05) and greater time in the border zone (515±9 vs. 452±11 sec, P<0.05) compared to C57 mice. After 6 weeks, time spent moving tended to decrease in C57‐WD compared to C57‐Chow (42% vs. 30%, P<0.10) while FVB‐WD and FVB‐chow had similar decreases (15% vs. 13% in FVB‐chow). Time in the border zone significantly increased by 8% in C57‐WD compared to a 20% decrease in C57‐chow. In contrast, border zone time decreased by 9% and 10% in FVB‐chow and FVB‐WD, respectively. In summary, in response to 6 weeks of WD, female FVB mice exhibit a more pronounced physical phenotype whereas female C57 mice are more prone to changes in activity and behavior. Overall, these results highlight important strain differences in response to a short‐term high fat diet in female mice

The Association between Trajectories of Loneliness and Physical Frailty in Chinese Older Adults: Does Age Matter?

Background: The present study aimed to examine age differences in the relationship between trajectories of loneliness and physical frailty among Chinese older adults. Methods: A total of 4618 participants aged ≥60 years old were taken from pooled data created from the 2011–2015 China Health and Retirement Longitudinal Study (CHARLS). Loneliness was assessed by a single question from the Centre for Epidemiological Studies scale, whereas physical frailty (PF) was examined by the physical frailty phenotype scale. We characterized trajectories of loneliness and PF using transition types and changes within the survey period. Results: Logistic regression models revealed that baseline loneliness was significantly related to remaining robust PF (OR = 0.55, 95% CI = 0.49–0.63, p < 0.001) and worsening in PF (OR = 1.17, 95% CI = 1.05–1.30, p < 0.01) at follow-up. Baseline PF status was also significantly related to the transitions in loneliness (worsen: OR = 1.41, 95% CI = 1.11–1.78, p < 0.01; improve: OR = 0.65, 95% CI = 0.47–0.91, p < 0.05). The cross-lagged panel model found that baseline PF or loneliness had a significant predictive effect on the changes in each other. The associations between trajectories of loneliness and PF were weakened with age and clustered in the under 75 age groups. Conclusions: Bidirectional associations may exist between trajectories of loneliness and PF among Chinese older adults. Interventions should mainly target the young-old to reduce the adverse reciprocal effects of loneliness and PF.

Harvester ant nest architecture is more strongly affected by intrinsic than extrinsic factors.

Behavior is shaped by genes, environment, and evolutionary history in different ways. Nest architecture is an extended phenotype that results from the interaction between the behavior of animals and their environment. Nests built by ants are extended phenotypes that differ in structure among species and among colonies within a species, but the source of these differences remains an open question. To investigate the impact of colony identity (genetics), evolutionary history (species), and the environment on nest architecture, we compared how two species of harvester ants, Pogonomyrmex californicus and Veromessor andrei, construct their nests under different environmental conditions. For each species, we allowed workers from four colonies to excavate nests in environments that differed in temperature and humidity for seven days. We then created casts of each nest to compare nest structures among colonies, between species, and across environmental conditions. We found differences in nest structure among colonies of the same species and between species. Interestingly, however, environmental conditions did not have a strong influence on nest structure in either species. Our results suggest that extended phenotypes are shaped more strongly by internal factors, such as genes and evolutionary history, and are less plastic in response to the abiotic environment, like many physical and physiological phenotypes.

Distinct Serum and Fecal Metabolite Profiles Linking With Gut Microbiome in Older Adults With Frailty.

Frailty is a critical aging-related syndrome but the underlying metabolic mechanism remains poorly understood. The aim of this study was to identify novel biomarkers and reveal potential mechanisms of frailty based on the integrated analysis of metabolome and gut microbiome. In this study, twenty subjects consisted of five middle-aged adults and fifteen older adults, of which fifteen older subjects were divided into three groups: non-frail, pre-frail, and frail, with five subjects in each group. The presence of frailty, pre-frailty, or non-frailty was established according to the physical frailty phenotype (PFP). We applied non-targeted metabolomics to serum and feces samples and used 16S rDNA gene sequencing to detect the fecal microbiome. The associations between metabolites and gut microbiota were analyzed by the Spearman’s correlation analysis. Serum metabolic shifts in frailty mainly included fatty acids and derivatives, carbohydrates, and monosaccharides. Most of the metabolites belonging to these classes increased in the serum of frail older adults. Propylparaben was found to gradually decrease in non-frail, pre-frail, and frail older adults. Distinct changes in fecal metabolite profiles and gut microbiota were also found among middle-aged adults, non-frail and frail older subjects. The relative abundance of Faecalibacteriu, Roseburia, and Fusicatenibacter decreased while the abundance of Parabacteroides and Bacteroides increased in frailty. The above altered microbes were associated with the changed serum metabolites in frailty, which included dodecanedioic acid, D-ribose, D-(-)-mannitol, creatine and indole, and their related fecal metabolites. The changed microbiome and related metabolites may be used as the biomarkers of frailty and is worthy of further mechanistic studies.

Revision of frailty assessment in kidney transplant recipients: Replacing unintentional weight loss with CT-assessed sarcopenia in the physical frailty phenotype

Kidney transplantation (KT) experts did not support the use of subjective unintentional weight loss to measure shrinking in the physical frailty phenotype (PFP); a clinically feasible and predictive measure of shrinking is needed. To test whether unintentional weight loss could be replaced by an assessment of sarcopenia using existing CT scans, we performed a prospective cohort study of adult KT recipients with original PFP (oPFP) measured at admission (December 2008-February 2020). We ascertained sarcopenia by calculating skeletal muscle index from available, clinically obtained CTs within 1-year pre-KT (male<50cm2 /m2 ; female<39cm2 /m2 ) and combined it with the original four components to determine new PFP (nPFP) scores. Frailty was classified by frailty score: 0: non-frail; 1-2: pre-frail; ≥3: frail. Mortality and graft loss hazard ratios (HRs) were estimated using adjusted Cox proportional hazard models. Model discrimination was quantified using Harrell's C-statistic. Among 1113 recipients, 18.6% and 17.1% were frail by oPFP and nPFP, respectively. Compared to non-frail recipients, frail patients by either PFP had higher risks of mortality (oPFP HR=1.67, 95% CI: 1.07-2.62, C=0.710; nPFP HR=1.68, 95% CI: 1.06-2.66, C=0.710) and graft loss (oPFP HR=1.67, 95% CI: 1.17-2.40, C=0.631; nPFP HR=1.66, 95% CI: 1.15-2.40, C=0.634) with similar discriminations. oPFP and nPFP are equally useful in risk prediction for KT recipients; oPFP may aid in screening patients for pre-KT interventions, while nPFP may assist in nuanced clinical decision-making.

Socioeconomic vulnerability and frailty among community-dwelling older adults: cross-sectional findings from longitudinal aging study in India, 2017\u201318

IntroductionThe Indian population is rapidly aging with huge proportion of illiterate and socioeconomically disadvantaged people and there is a dearth of research on the relationships between factors of socioeconomic vulnerability and frailty in older people. The present study examined the cross-sectional associations between socioeconomic vulnerability and physical frailty in community-dwelling older individuals in India.Materials and methodsThe data for the study were obtained from the Longitudinal Aging Study in India (LASI), which was conducted in 2017–18. The effective sample size was 14,652 older males and 15,899 older females aged 60 and over. The outcome variable was physical frailty phenotype measured from exhaustion, unintentional weight loss, weak grip strength, low physical activity, and slow walking time. The main explanatory variable was vulnerability status based on education, wealth and caste. The study carried out bivariate analysis to observe the association between vulnerability status and physical frailty. Further, multivariable binary logistic regression analysis was conducted to fulfil the objective of the study.ResultsA proportion of 10.5 and 14.4% of older males and females respectively were in the overall vulnerable category. The prevalence of physical frailty was high among older males from vulnerable population (31.4% vs 26.9%; p < 0.001). The adjusted estimates from multivariate analysis revealed that older adults from vulnerable category had 14% significantly higher odds of being frail in comparison to non-vulnerable category [AOR: 1.14; CI: 1.06,1.24]. The adjusted model further revealed that there were no significant gender differentials in physical frailty among older adults. Model-3 (adjusted model) revealed that older males and females from vulnerable population had 18% [AOR: 1.18; CI: 1.04,1.34] and 8% [AOR: 1.08; CI: 1.01,1.21] significantly higher odds of being physically frail in comparison to older males from non-vulnerable population respectively.ConclusionsAdverse socioeconomic circumstances such as low education, lower wealth and caste status that are associated with increased prevalence of physical frailty raise urgent questions both for public health practitioners and clinicians. The current findings may help to adapt public policies focusing on screening physical frailty in the clinical settings, especially among vulnerable populations as a marker of a possibly reversible vulnerability to adverse outcomes in old age.

Conceptualizing Biological Aging and Frailty in Orthopaedics: A Framework for Clinical Practice.

Biological aging can best be conceptualized clinically as a combination of 3 components: frailty, comorbidity, and disability. Despite advancements in the understanding of senescence, chronological age remains the best estimate of biological age. However, a useful exercise for practitioners is to look beyond chronological age in clinical and surgical decision-making. A chronologically aging person does not age biologically at the same rate. The best way to understand frailty is to consider it as a physical phenotype. Physical optimization should parallel medical optimization before elective surgery. The poorer the host (both in terms of bone quality and propensity for healing), the more robust the implant construct must be to minimize reliance on host biology.

Correction to: Response to Letter Regarding Article “Characterizing Gender Differences in Physical Frailty Phenotypes in Heart Failure”

Correction to: Response to Letter Regarding Article “Characterizing Gender Differences in Physical Frailty Phenotypes in Heart Failure”

Long-Term Trajectories of Frailty and Its Components After Kidney Transplantation.

Frailty is common and associated with poor outcomes among kidney transplant (KT) recipients. While frailty improves in the first 3 months post-KT with restored kidney function, longer-term trajectories are likely to plateau/decline due to aging and other stressors (eg, immunosuppression). We evaluated longer-term post-KT trajectories of the physical frailty phenotype (PFP) and its components in adult patients at 2 centers. PFP components were measured at admission, 1, 3, 6 months, 1 year, and annually thereafter post-KT. We used adjusted mixed-effects models to describe repeated measures of continuous components (weight, gait speed, grip strength, activity) and generalized estimating equations to quantify longitudinal, binomial response patterns (PFP; exhaustion). Among 1 336 recipients (mean age = 53) followed for a median of 1.9 years (interquartile range [IQR] = 0.1-3.2), likelihood of frailty declined in the first 2.5 years post-KT (adjusted odds ratio [aOR] = 0.96, 95% confidence interval [CI]: 0.95, 0.98), but increased after 2.5 years post-KT (aOR = 1.03, 95% CI: 1.00, 1.05). In the first 2.5 years post-KT, recipients demonstrated increases in weight (0.4 lbs/month, 95% CI: 0.3, 0.5), grip strength (0.2 kg/month, 95% CI: 0.1, 0.2), and activity (23.9 kcal/month, 95% CI: 17.5, 30.2); gait speed remained stable (-0.01 s/month, 95% CI: 0.01, 0.003). Additionally, likelihood of becoming exhausted declined post-KT (OR = 0.99, 95% CI: 0.98, 1.00). After 2.5 years post-KT, recipients demonstrated decreased grip strength (-0.07 kg/month, 95% CI: -0.12, -0.01) and activity (-20 kcal/month, 95% CI: -32.3, -8.2); they had stable weight (-0.003 lbs/month, 95% CI: -0.17, 0.16), gait speed (-0.003 s/month, 95% CI: -0.02, 0.01), and likelihood of becoming exhausted (OR = 1.01, 95% CI: 0.99, 1.02). Despite frailty improvements in the first 2.5 years, recipients' frailty worsened after 2.5 years post-KT. Specifically, they experienced gains in strength, activity, and exhaustion in the first 2.5 years post-KT, but declined in strength and activity after 2.5 years post-KT while experiencing persistent slowness. Clinicians should consider monitoring recipients for worsening frailty after 2.5 years despite shorter-term improvements.

Implementación del protocolo ERAS en ancianos sometidos a resección hepática

BackgroundThe increase of quality of life, the improvement in the perioperative care programs, the use of the frailty index, and the surgical innovation has allowed to access of complex abdominal surgery for elderly patients like liver resection. Despite of this, in patients aged 70 or older there is a limitation for the implementation ERAS protocols.The aim of this study is to evaluate the implementation ERAS protocol on elderly patients (≥70years) undergoing liver resection. MethodsA prospective cohort study of patients who underwent liver resection from December 2017 to December 2019 with an ERAS program. We compare the outcomes in patients ≥70years (G≥70) versus <70years (G<70). The frailty was measured with the Physical Frailty Phenotype score. ResultsA total of 101 patients were included; 32 of these (31.6%) were patients ≥70years. 90% of the both groups had performed >70% of the ERAS. Oral diet tolerance and mobilization on the first postoperative day were quicker in <70years group. The hospital stay was similar in both groups (3.07days/2.7days). Morbidity and mortality were similar; ClavienI-II (G≥70: 41% vs G<70: 30.5%) and Clavien ≥III (G≥70: 6% vs G<70: 8.5%), like hospital readmissions. Mortality was <1%. ERAS protocol compliance was associated with a decrease in complications (ERAS <70%: 80% vs ERAS >90%: 20%; p=0.02) and decrease in severity of complications in both study groups. Frailty was found in 6% of the elderly group; the only patient who died had a frailty index of 4. ConclusionImplementation of ERAS protocol for elderly patients is possible, with major improvements in perioperative outcomes, without an increase in morbidity, mortality neither readmissions.

Differential expression of the neuronal CB1 cannabinoid receptor in the hippocampus of male Ts65Dn Down syndrome mouse model

Down syndrome (DS) or Trisomy 21 is the most common genetic cause of mental retardation with severe learning and memory deficits. DS is due to the complete or partial triplication of human chromosome 21 (HSA21) triggering gene overexpression and protein synthesis alterations responsible for a plethora of mental and physical phenotypes. Among the diverse brain target systems that affect hippocampal-dependent learning and memory deficit impairments in DS, the upregulation of the endocannabinoid system (ECS), and notably the overexpression of the cannabinoid type-1 receptor (CB1), seems to play a major role. Combining various protein and gene expression targeted approaches using western blot, qRT-PCR and FISH techniques, we investigated the expression pattern of ECS components in the hippocampus (HPC) of male Ts65Dn mice. Among all the molecules that constitute the ECS, we found that the expression of the CB1 is altered in the HPC of Ts65Dn mice. CB1 distribution is differentially segregated between the dorsal and ventral part of the HPC and within the different cell populations that compose the HPC. CB1 expression is upregulated in GABAergic neurons of Ts65Dn mice whereas it is downregulated in glutamatergic neurons. These results highlight a complex regulation of the CB1 encoding gene (Cnr1) in Ts65Dn mice that could open new therapeutic solutions for this syndrome.

Lipidomic signatures from physically frail and robust older adults at hospital admission

Identifying serum biomarkers that can predict physical frailty in older adults would have tremendous clinical value for primary care, as this condition is inherently related to poor quality of life and premature mortality. We compared the serum lipid profile of physically frail and robust older adults to identify specific lipid biomarkers that could be used to assess physical frailty in older patients at hospital admission. Forty-three older adults (58.1% male), mean (range) age 86.4 (78–100 years) years, were classified as physically frail (n = 18) or robust (n = 25) based on scores from the Short Physical Performance Battery (≤ 6 points). Non-targeted metabolomic study by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis with later bioinformatics data analysis. Once the significantly different metabolites were identified, the KEGG database was used on them to establish which were the metabolic pathways mainly involved. Area under receiver-operating curve (AUROC) analysis was used to test the discriminatory ability of lipid biomarkers for frailty based on the Short Physical Performance Battery. We identified a panel of five metabolites including ceramides Cer (40:2), Cer (d18:1/20:0), Cer (d18:1/23:0), cholesterol, and phosphatidylcholine (PC) (14:0/20:4) that were significantly increased in physically frail older adults compared with robust older adults at hospital admission. The most interesting in the physically frail metabolome study found with the KEGG database were the metabolic pathways, vitamin digestion and absorption, AGE-RAGE signaling pathway in diabetic complications, and insulin resistance. In addition, Cer (40:2) (AUROC 0.747), Cer (d18:1/23:0) (AUROC 0.720), and cholesterol (AUROC 0.784) were identified as higher values of physically frail at hospital admission. The non-targeted metabolomic study can open a wide view of the physically frail features changes at the plasma level, which would be linked to the physical frailty phenotype at hospital admission. Also, we propose that metabolome analysis will have a suitable niche in personalized medicine for physically frail older adults.

Association Between Frailty and Inpatient Services Utilization Among Older Adults in Rural China: The Mediating Role of Multimorbidity.

IntroductionDeveloped and developing countries have different health systems and disease patterns. There is little evidence that frailty is related to inpatient services utilization in developing countries. In addition, the underlying mechanism of this relationship also remains unclear. This study aimed to examine the association between frailty and inpatient services utilization, and further explore whether multimorbidity play a mediating role in this association.MethodsA total of 3,242 rural older adults aged 60 and older were included in the analysis. Frailty was measured by the physical frailty phenotype (PFP). Multimorbidity and inpatient services utilization was measured based on participants' self-report and validated by village doctors. Ordered logistic regression analyses were performed to examine the association between frailty, multimorbidity and inpatient services utilization. Bootstrap analysis was further to explore the mediation effect of multimorbidity on frailty and inpatient services utilization.ResultsThe utilization of inpatient services was 20.1% (one: 15.8%, two or more: 4.3%). The prevalence of prefrailty and frailty was 64.7 and 18.1%, respectively. Frail older adults experienced a higher risk of multimorbidity and inpatient services utilization. Multimorbidity partially mediated the association between frailty and inpatient services utilization [95% confidence interval (CI): 0.005-0.016, p < 0.001]. The mediating effect of multimorbidity accounted for 19.0% of the total effect.ConclusionsAmong Chinese rural older adults, frailty is associated with higher inpatient services utilization, and multimorbidity mediates this association. Recommendations are to increase frailty risk screening, chronic disease monitoring, and to do timely interventions.

Outcomes of Frail Patients While Waiting for Kidney Transplantation: Differences between Physical Frailty Phenotype and FRAIL Scale.

Frailty is associated with poorer outcomes among patients waiting for kidney transplantation (KT). Several different tools to measure frailty have been used; however, their predictive value is unknown. This is a prospective longitudinal study of 449 KT candidates evaluated for frailty by the Physical Frailty Phenotype (PFP) and the FRAIL scale. During the study period, 296 patients received a KT, while 153 remained listed. Patients who did not get receive a transplant were more frequently frail according to PFP (16.3 vs. 7.4%, p = 0.013). Robust patients had fewer hospital admissions during the 1st year after listing (20.8% if PFP = 0 vs. 43.4% if ≥1, and 27.1% if FRAIL = 0 vs. 48.9% if ≥1) and fewer cardiovascular events (than FRAIL ≥ 1) or major infectious events (than PFP ≥ 1). According to PFP, scoring 1 point had an impact on patient survival and chance of transplantation in the univariate analysis. The multivariable analysis corroborated the result, as candidates with PFP ≥ 3 had less likelihood of transplantation (HR 0.45 [0.26–0.77]). The FRAIL scale did not associate with any of these outcomes. In KT candidates, pre-frailty and frailty according to both the PFP and the FRAIL scale were associated with poorer results while listed. The PFP detected that frail patients were less likely to receive a KT, while the FRAIL scale did not.

Background and Design of the Biological and Physiological Mechanisms of Symptom Clusters in Heart Failure (BIOMES-HF) Study

BackgroundSymptoms, which often cluster together, are a significant problem in heart failure (HF). There is considerable heterogeneity in symptom burden, particularly in the vulnerable transition period after a hospitalization for HF, and the biological underpinnings of symptoms during transitions are unclear. The purpose of this article is to describe the background and design of a study that addresses these knowledge gaps, entitled Biological and Physiological Mechanisms of Symptom Clusters in Heart Failure (BIOMES-HF). Methods and ResultsBIOMES-HF is a prospective gender- and age-balanced longitudinal study of 240 adults during the 6-month transition period after a HF hospitalization. The aims are to (1) identify clusters of change in physical symptoms, (2) quantify longitudinal associations between biomarkers and physical symptoms, and (3) quantify longitudinal associations between physical frailty and physical symptoms among adults with HF. We will measure multiple symptoms, biomarkers, and physical frailty at discharge and then at 1 week and 1, 3, and 6 months after hospitalization. We will use growth mixture modeling and longitudinal mediation modeling to examine changes in symptoms, biomarkers, and physical frailty after HF hospitalization and associations therein. ConclusionsThis innovative study will advance HF symptom science by using a multibiomarker panel and the physical frailty phenotype to capture the multifaceted nature of HF. Using advanced quantitative modeling, we will characterize heterogeneity and identify potential mechanisms of symptoms in HF. As a result, this research will pinpoint amenable targets for intervention to provide better, individualized treatment to improve symptom burden in HF. Lay SummaryAdults with heart failure may have significant symptom burden. This study is designed to shed light on our understanding of the role of biological and physiological mechanisms in explaining heart failure symptoms, particularly groups of co-occurring symptoms, over time. We explore how symptoms, biomarkers, and physical frailty change after a heart failure hospitalization. The knowledge generated from this study will be used to guide the management and self-care for adults with heart failure.

Acoustofluidic interferometric device for rapid single-cell physical phenotyping.

High-throughput single-cell analysis based on physical properties (such as morphology or mechanics) is emerging as a powerful tool to inform clinical research, with a great potential for translation towards diagnosis. Here we present a novel microfluidic approach adopting acoustic waves to manipulate and mechanically stimulate single cells, and interferometry to track changes in the morphology and measure size, deformability, and refractive index of non-adherent cells. The method is based on the integration within the acoustofluidic channel of a low-finesse Fabry-Perot resonator, providing very high sensitivity and a speed potentially suitable to obtain the high-throughput necessary to handle the variability stemming from the biological diversity of single cells. The proposed approach is applied to a set of different samples: reference polystyrene beads, algae and yeast. The results demonstrate the capability of the acoustofluidic interferometric device to detect and quantify optomechanical properties of single cells with a throughput suitable to address label-free single-cell clinical analysis.

Predicting Physical Appearance from DNA Data-Towards Genomic Solutions.

The idea of forensic DNA intelligence is to extract from genomic data any information that can help guide the investigation. The clues to the externally visible phenotype are of particular practical importance. The high heritability of the physical phenotype suggests that genetic data can be easily predicted, but this has only become possible with less polygenic traits. The forensic community has developed DNA-based predictive tools by employing a limited number of the most important markers analysed with targeted massive parallel sequencing. The complexity of the genetics of many other appearance phenotypes requires big data coupled with sophisticated machine learning methods to develop accurate genomic predictors. A significant challenge in developing universal genomic predictive methods will be the collection of sufficiently large data sets. These should be created using whole-genome sequencing technology to enable the identification of rare DNA variants implicated in phenotype determination. It is worth noting that the correctness of the forensic sketch generated from the DNA data depends on the inclusion of an age factor. This, however, can be predicted by analysing epigenetic data. An important limitation preventing whole-genome approaches from being commonly used in forensics is the slow progress in the development and implementation of high-throughput, low DNA input sequencing technologies. The example of palaeoanthropology suggests that such methods may possibly be developed in forensics.

Frailty in kidney transplant candidates: a comparison between physical frailty phenotype and FRAIL scales.

Frailty is common among advanced chronic kidney disease (CKD) patients who are kidney transplant (KT) candidates, and predisposes to poor outcomes after transplantation. However, frailty is not routinely measured during pretransplant work-up and it is unknown which metric should be used in this specific population. Our aim was to establish frailty prevalence in KT candidates according to different frailty scales. Prospective longitudinal study of 451 KT candidates evaluated for frailty by both Physical Frailty Phenotype (PFP) and FRAIL scale at the time of inclusion on the KT waiting list. Clinical and functional characteristics including sociodemographics, comorbidities, disability and nutritional status were recorded. Agreement between PFP and FRAIL scales as well as dissonant patients were analyzed. Mean age was 60.9years and 31.7% were female. Comorbidity burden among patients was high, with 36.9% and 16.2% presenting with diabetes and ischemic coronary disease, respectively. Disabilities were also frequent. More than 70% of patients presented with ≥ 1 PFP criteria while this percentage for ≥ 1 FRAIL criteria was 45.4%. Agreement between PFP and FRAIL was not good (kappa index 0.317). There were 132 patients who were pre-frail or frail according to PFP but non-frail according to the FRAIL scale and they presented with fewer comorbidities and less disability. Frailty is frequent in advanced CKD patients, although its prevalence may vary according to different scales. Agreement between PFP and FRAIL scale is not good, and FRAIL scale might misclassify as robust patients those frail/prefrail patients who are in better health conditions.