Validity of estimating muscle and fat volume from a single MRI section in older adults with sarcopenia and sarcopenic obesity.

AIM: To determine if there is a correlation between the cross-sectional areas (CSAs) in a single section and the volumes of muscles and fat in the thigh of sarcopenic and sarcopenic obesity (SO) populations using magnetic resonance imaging (MRI), and to assess the correlation between thigh MRI data and patient health status, i.e., normal, obese, sarcopenia, and SO. MATERIALS AND METHODS: One hundred and ninety community-dwelling older adults were recruited and categorised into four subgroups based on Asian established criteria: normal, obese, sarcopenia, and SO. MRI images were acquired and muscles, subcutaneous fat (SF), and intermuscular fat (IMF) were automatically segmented in the thighs. Volumes of muscles and fat were calculated for the middle third of the thigh, while CSAs were assessed using a single section at 50% femur length. RESULTS: Correlation between CSA and volume were significantly high (p<0.001) for all components of muscle (0.907), SF (0.963), and IMF (0.939). Thigh CSA and volume both correlated significantly with a clinical diagnosis of normal, obesity, sarcopenia, and SO (p<0.03). CONCLUSIONS: A single CSA at 50% of femur length yields good estimation of muscle and fat volume in the thighs of older adults and correlates closely with the clinical criteria for sarcopenia and SO. This has the potential to greatly reduce costs, scan time, and post-processing time in clinical practice for the prediction of these conditions.

A SERS and electrical sensor from gas-phase generated Ag nanoparticles self-assembled on planar substrates.

Optical excitation of coupled plasmonic nanoparticles supports intense localized electromagnetic "hot-spots" which enable a variety of surface enhanced spectroscopies with the best known example being surface enhanced Raman scattering (SERS), currently of great interest for sensing applications. In this study, we present a novel SERS and electrical dual transduction chemical sensor based on gas-phase generated, negatively charged, silver nanoparticles self-assembled on glass slide forming a close-packed plasmonic monolayer thin-film that supports both SERS and electrical sensing. We demonstrate broad tunability of the localized surface plasmon resonance (LSPR) of the close-packed plasmonic nanoparticle monolayer thin-film sensors through control of the nanoparticle (NP) deposition time which directly influences the plasmonic coupling between neghibouring NPs. This broad tunability supports strong SERS activity from visible to near infrared (NIR) excitation wavelengths. We performed SERS and electrical measurements of a non-resonant molecule 4-mercaptobenzonitrile (4-MBN) as a sample Raman reporter molecule to determine the SERS enhancement factor of our SERS substrate. We measured an average SERS enhancement factor of 10(7) from our close-packed plasmonic nanoparticle monolayer thin-film sensor. Films which were grown below or above one nanoparticle monolayer both exhibited significantly lower SERS performance in one or more of SERS enhancement factor (EF), uniformity or repeatability. Our close-packed plasmonic nanoparticle monolayer thin-film sensors are highly uniform from point-to-point across the entire substrate and showed good reproducibility from batch-to-batch. These qualities are highly desirable for quantifiable detection of chemical and biological molecules. As an example application, this type of substrates provides an affordable and reliable sensing and identification capability for combatting new and emerging chemical and biological threats in support of security applications.

Onychomadesis following childhood hand-foot-mouth disease in two pairs of siblings- a familial predisposition?

Onychomadesis is presented in four patients as a result of hand-foot-mouth disease.

Association of Intrinsic Capacity with Frailty, Physical Fitness and Adverse Health Outcomes in Community-Dwelling Older Adults.

BACKGROUND: Intrinsic capacity (IC) and frailty are complementary in advancing disability prevention through maintaining functionality. OBJECTIVES: We examined the relationship between IC and frailty status at baseline and 1-year, and evaluated if IC decline predicts frailty onset among robust older adults. The secondary objectives investigated associations between IC, physical fitness and health-related outcomes. DESIGN: Prospective cohort study. SETTING: Community-based assessments. PARTICIPANTS: Older adults aged>55 years, who were independent in ambulation (walking aids permitted). MEASUREMENTS: 5 domains of IC were assessed at baseline: locomotion (Short Physical Performance Battery, 6-minute walk test), vitality (nutritional status, muscle mass), sensory (self-reported hearing and vision), cognition (self-reported memory, age- and education adjusted cognitive performance), psychological (Geriatric Depression Scale-15, self-reported anxiety/ depression). Composite IC (0-10) was calculated, with higher scores representing greater IC. Frailty status was based on modified Fried criteria, with frailty progression defined as incremental Fried score at 1-year. RESULTS: 809 participants (67.6+6.8 years) had complete data for all 5 IC domains. 489 (60.4%) participants were robust but only 213 (26.3%) had no decline in any IC domain. Pre-frail and frail participants were more likely to exhibit decline in all 5 IC domains (p<0.05), with decremental composite IC [9 (8-9), 8 (6-9), 5.5 (4-7.5), p<0.001] across robust, prefrail and frail. IC was significantly associated with fitness performance, independent of age and gender. Higher composite IC reduced risk for frailty progression (OR=0.62, 95% CI 0.48-0.80), and reduced frailty onset among robust older adults (OR=0.53, 95% CI 0.37-0.77), independent of age, comorbidities and social vulnerability. Participants with higher IC were less likely to experience health deterioration (OR=0.70, 95% CI 0.58-0.83), falls (OR=0.76, 95% CI 0.65-0.90) and functional decline (OR=0.64, 95% CI 0.50-0.83) at 1-year. CONCLUSION: Declining IC may present before frailty becomes clinically manifest, increasing risk for poor outcomes. Monitoring of IC domains potentially facilitates personalized interventions to avoid progressive frailty.

Prostatic stromal tumour of uncertain malignant potential treated with robotic-assisted radical prostatectomy: medium-term oncological and functional outcome of two cases.

Stromal tumour of uncertain malignant potential (STUMP) is a rare tumour of the prostate with variable and unpredictable risk and clinical progression. There is no clear consensus on how it should be managed. We describe two cases of patients who presented to their general practitioners with raised prostate-specific antigen in one instance and an abnormal digital rectal examination in the other. Biopsies were carried out and a diagnosis of STUMP was made. Both cases were managed with robot-assisted radical prostatectomy and after 4.8 years of follow-up, there has not been any recurrence. This is the first reported UK case in which STUMP has been successfully managed with robotic surgery with excellent medium-term results. Radical prostatectomy can be used to treat STUMP tumour with good oncological and functional outcomes.

Singapore Clinical Practice Guidelines For Sarcopenia: Screening, Diagnosis, Management and Prevention.

OBJECTIVES: To present the local evidence and final recommendations of the Clinical Practice Guidelines workgroup convened by the Chapter of Geriatricians and the Society for Geriatric Medicine Singapore. The aim is to develop contextualized evidence-based recommendations that facilitate adoption of the Asian Working Group for Sarcopenia (AWGS) 2019 consensus into current practice in Singapore. METHODS: The workgroup drew upon the AWGS'2019 consensus, updated literature review of Singapore studies till 31 Dec 2020, and evidence from recent systematic reviews. From 40 local studies included for data extraction, we constructed evidence tables organized as: definition and epidemiology; diagnosis and evaluation; and treatment and intervention. Twenty recommendations - case-finding, diagnosis, treatment, prevention, research - were developed, and graded for strength and quality using the GRADE approach. Consensus from an expert panel(N=23) was achieved after two rounds of the modified Delphi process. RESULTS: The local prevalence of sarcopenia among community-dwelling older adults ranged from 13.6% to 25%. Most studies adopted the AWGS'2019 and AWGS'2014 criteria. Reported case finding tools include SARC-F, calf circumference (CC) and SARC-CalF. Gender-specific AWGS cut-offs for appendicular skeletal mass were used to define low muscle mass. Different protocols and dynamometers were used to assess handgrip strength, whilst gait speed and 5-times chair stand were commonly used to assess physical performance. RECOMMENDATIONS: We conditionally recommend a case-finding approach in at-risk older adults using validated case-finding tools. Screen-positive individuals should be assessed for 'possible sarcopenia' and underlying causes. For diagnosis, we conditionally recommend using the AWGS'2019 algorithm, and dual-energy X-ray absorptiometry when necessary to determine low lean mass for a confirmatory diagnosis of sarcopenia. For treatment, we strongly recommend resistance-based exercises and conditionally recommend a quality protein-rich diet/protein supplementation, with Vitamin D supplementation for insufficiency (<30 micrograms/L). For prevention, we recommend regular resistance-based physical activity and adequate protein intake (≥1.0g/kg bodyweight). We encourage more research to address local evidence gaps.

Dermatology referrals in an East Asian tertiary hospital: a need for inpatient medical dermatology.

BACKGROUND: Within hospitals, there is a need for dermatological expertise, as hospitalized patients have a wider spectrum of severe and serious dermatological conditions, associated with significant morbidity. AIM: To characterize the patient profile and referral pattern of inpatient dermatology consultations, and to evaluate the diagnostic accuracy of non-dermatologists. METHODS: This was a retrospective study reviewing all inpatient referrals for dermatology consultations during a 1-year period from July 2005 to June 2006 (inclusive), at the largest multi-disciplinary tertiary hospital in Singapore. RESULTS: Of the 731 referrals made for dermatology consultations, 26.9% of patients had ≥ 3 important underlying comorbidities. Eczema/dermatitis (33.1%; n = 242) and cutaneous infections (23.4%; n = 171) accounted for over half of the dermatological consultations, followed by cutaneous adverse drug reactions (12.3%; n = 90). The provisional diagnoses of the referring doctors agreed with the final diagnoses confirmed by dermatologists in only 30.2% of all referrals; incorrect diagnoses were made in 35.2% of cases, and no provisional diagnoses were made in the remaining 34.6% of cases. Most misdiagnosed skin diseases were in fact common dermatoses (such as eczemas, cutaneous infections, drug rash) that required only standard treatment. CONCLUSION: Our study reiterates the importance of inpatient medical dermatology in terms of both service and education. There should be continual efforts to ensure that dermatologists have the highest level of training and experience in medical dermatology, to provide collaborative optimum care for hospitalized patients with dermatological diseases.

Australian guidelines for the assessment of iron overload and iron chelation in transfusion-dependent thalassaemia major, sickle cell disease and other congenital anaemias.

Iron overload is the most important cause of mortality in patients with thalassaemia major. Iron chelation is therefore a critical issue in the management of these patients and others with transfusion-dependent haemoglobinopathies and congenital anaemias. In recent years, significant developments have been made in the assessment of iron overload, including the use of magnetic resonance imaging for measuring liver and cardiac iron. Advances in the modalities available for iron chelation, with the advent of oral iron chelators including deferiprone and deferasirox in addition to parenteral desferrioxamine, have expanded treatment options. A group of Australian haematologists has convened to formulate guidelines for managing iron overload on the basis of available evidence, and to describe best consensus practice as undertaken in major Australian Haemoglobinopathy units. The results of their discussions are described in this article, with the aim of providing guidance in the management of iron overload in these patients.

Clinical effects of prolonged application time of an in-office bleaching gel.

OBJECTIVE: The aim of this study was to evaluate whether the use of a gel applied for 1 × 45 minutes would have the same bleaching rate and tooth sensitivity levels when compared with 3 × 15-minute applications. METHODS: In-office bleaching was performed in 30 participants with 35% hydrogen peroxide gel. In one group (n=15; 3 x 15 minutes), the bleaching agent was refreshed every 15 minutes, three times at each bleaching appointment. In the other group (n=15; 1 x 45 minutes) the gel was left undisturbed on the buccal surfaces of all teeth for 45 minutes at each bleaching appointment. This protocol was repeated after one week. The bleaching evaluation was completed by two blinded, calibrated evaluators who compared the baseline color of the maxillary anterior teeth with a value-oriented shade guide after each period. The patients recorded the tooth sensitivity on a 0-4 scale. The color changes were evaluated by appropriate tests (α=0.05). The percentage of patients with tooth sensitivity and its intensity were also statistically analyzed (α=0.05), respectively. RESULTS: The use of gel for a single 45-minute period (1 x 45 minutes) decreased the bleaching efficacy (p<0.05) 86.7%, and 100% of patients from the 3 × 15-minute and 1 × 45-minute groups, respectively, experienced tooth sensitivity (p=0.22). The intensity of sensitivity was lower for the 3 × 15-minute applications (p=0.04). CONCLUSIONS: A 35% hydrogen peroxide gel for in-office bleaching preferably should be applied in three 15-minute applications because 1 × 45 minutes reduces the bleaching speed and slightly increases the intensity of tooth sensitivity.

Limited Etching Time Increases Self-adhesive Resin Cement Adhesion to Enamel.

AIM: To evaluate the influence of different enamel etching times on the bond strength of two self-adhesive resin cements (RCs) with and without thermocycling (TMC). METHODS: One hundred twenty bovine teeth were used. Blocks of enamel (8×4×2mm) were obtained, polished, and randomly divided into two groups, according to the RC used: MaxCem Elite or RelyX U200. Groups were subdivided into four groups (n=16), according to the etching time: Control (0 seconds), 5 seconds, 10 seconds, and 20 seconds. Three RC cylinders (1-mm diameter) were built on each enamel block. The specimens were submitted to two storage conditions: 24 hours in distilled water or TMC (5000 cycles/5°C-55°C). Afterward, the specimens were submitted to the shear bond strength (SBS) test. The failure modes and adhesive interfaces were analyzed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Data were analyzed with three-way analysis of variance (ANOVA) and Tukey test (α=0.05). RESULTS: Etching increased the SBS for both the RCs,especially forthe groups etched for 5 and 10 seconds. TMC affected negatively the SBS of the control groups (p<0.05). No resin tags were observed in control groups, and the formation of tags was time dependent. CONCLUSION: The 10 seconds etching time was more effective in increasing the enamel-resin bond strength. TMC negatively affected bond strength in specimens without acid etching.

A Non-Controlled Study of a Multi-Factorial Exercise and Nutritional Intervention to Improve Functional Performance and Prevent Frailty Progression in Community-Dwelling Pre-Frail Older Adults.

Background: Preventing frailty is important to avoid adverse health outcomes. Intervention studies have largely focused on frail elderly, although the intermediate pre-frail state may be more amenable to improvement. Objectives: This study aims to assess how physical performance may change among pre-frail elderly enrolled in a pragmatic non-controlled exercise and nutritional intervention programme. Methods: This is a non-controlled study involving a 4-month exercise and nutritional intervention for community dwelling pre-frail older adults. Pre-frailty was defined as the presence of 1 or 2 positive responses on the FRAIL questionnaire, or evidence of weak grip strength (<26kg for males; <18kg for females) or slow gait speed (<0.8m/s) amongst participants who were asymptomatic on FRAIL. Physical performance in flexibility, grip and lower limb strength, endurance, balance, and Short Physical Performance Battery were measured at 3 time-points: baseline, 3-month from recruitment (without intervention), and immediate post-intervention. Repeated measures mixed model analysis was performed to compare physical performance measures across the 3 time-points. Results: 94 pre-frail participants were eligible for intervention, of whom 59 (mean age = 70.9±7.2 years) were ready for the post-intervention review. 21 (35.6%) transitioned to robust phenotype while 32 (54.2%) remained as pre-frail. Significant improvement post-intervention was observed in lower limb strength and power, evident on reduction in time taken for 5 sit-to-stand repetitions (0.46±0.20s, p=0.03). There was no significant change to the other physical performance measures examined. Conclusion: We observed reversibility of pre-frailty, and the benefit of multi-component intervention in improving physical performance of pre-frail older adults. The findings in this non-controlled study will need to be corroborated with future controlled trials.

Observational study of iron overload as assessed by magnetic resonance imaging in an adult population of transfusion-dependent patients with beta thalassaemia: significant association between low cardiac T2* < 10 ms and cardiac events.

BACKGROUND: Thalassaemia major patients usually die from cardiac haemosiderosis. Improved strategies are required to modify this risk. AIMS: To assess the significance of cardiac iron overload in patients with beta thalassaemia. METHOD: Observational study of cardiac iron overload as assessed by magnetic resonance imaging (MRI) cardiac T2* relaxometry in 30 adult patients with transfusion-dependent beta thalassaemia. RESULTS: 11/30 patients (37%) had cardiac T2* < 10 ms, 8/30 (27%) in range 10-20 ms and 11/30 (37%) > 20 ms. There was significant inverse correlation between T2* values and values for serum ferritin (SF) and liver iron concentration (LIC) and positive correlation with left ventricular ejection fraction (LVEF). Median LVEF values were 49% in patients with T2* < 10 ms and 58% in patients with T2* > 10 ms (P = 0.02). Very low T2* values <10 ms were strongly associated with the occurrence of cardiac events (congestive heart failure, arrhythmia, cardiac death): occurring in 5/11 patients with T2* < l0 ms and in 0/19 in patients with T2* > 10 ms (P = 0.003 Fisher's exact test; P = 0.002 log rank Kaplan-Meier time to event analysis). There was no significant association between T2* < 10 ms or cardiac events and traditional measures of iron overload, such as SF levels >2500 mg/L and LIC (evaluated at thresholds of >7 or >15 mg/g dry weight). CONCLUSION: Very low cardiac T2* values <10 ms are common in adults with beta thalassaemia and are significantly associated with risk of cardiac events. This permits the use of individually targeted chelation strategies which are more effective in removing cardiac iron.

Muscle Strength Definitions Matter: Prevalence of Sarcopenia and Predictive Validity for Adverse Outcomes Using the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) Criteria.

BACKGROUND: EWGSOP2 criteria for sarcopenia recommends the use of either handgrip strength (GS) or 5-times repeated chair stand test (RCS) as a muscle strength measure. We aim to compare the impact of different muscle strength definitions on sarcopenia prevalence and predictive validity for 2-year outcomes, using the EWGSOP2 clinical algorithm. METHODS: We studied 200 community-dwelling older adults, comparing sarcopenia prevalence using three muscle strength definitions: 1) maximum GS (Asian Working Group cutoffs); 2) RCS-1 (standard cutoff >15s); and 3) RCS-2 (ROC-derived cutoff >12.5s). Two-year outcomes include: 1) Incident frailty (modified Fried criteria); 2) Physical performance [Short Physical Performance Battery (SPPB) score <10]; and 3) Quality of life [EuroQol-5 dimension (EQ-5D) <25th percentile]. We performed logistic regression on 2-year outcomes adjusted for age, gender, cognition and mood. RESULTS: Prevalence of confirmed sarcopenia was 14.5%, 4% and 9% for GS, RCS-1 and RCS-2 respectively. For 2-year outcomes (N=183), RCS-2 predicted incident frailty (OR: 5.7, 95% CI 1.4-22.8, p=0.013), low SPPB (OR: 4.4, 95% CI 1.4-13.1, p=0.009), and trended towards predicting low QOL (OR: 2.1, 95% CI 0.9-4.9, p=0.095). In contrast, GS and RCS-1 did not predict frailty nor low QOL, but predicted low SPPB only (GS: OR 3.8, 95% CI 1.3-10.6, p=0.01; RCS-1: OR: 8.8, 95% CI 2.2-35.0, p=0.002). CONCLUSIONS: Sarcopenia prevalence varies with muscle strength definitions, with GS being significantly higher vis-à-vis RCS definitions. Our results also support the use of population-specific over standard cutoffs for RCS to obtain intermediate estimates of sarcopenia prevalence and the best predictive validity for two-year outcomes.

Grip Strength Criterion Matters: Impact of Average Versus Maximum Handgrip Strength on Sarcopenia Prevalence and Predictive Validity for Low Physical Performance.

IMPORTANCE: Muscle strength has been elevated to the forefront of sarcopenia diagnosis, with handgrip strength the preferred measure. Extant handgrip protocols adopt different handgrip strength (HGS) criteria. Paucity of direct comparison studies assessing the impact of HGS criterion on prevalence of sarcopenia and predictive validity on physical performance contributes to the lack of standardisation of HGS criteria in sarcopenia diagnosis. OBJECTIVES: Our study aims to compare the effect of average (HGSave) versus maximum (HGSmax) HGS criterion on: (1) prevalence of low HGS and sarcopenia; and (2) association with physical performance at baseline and at 2 years. METHODS: We recruited 200 community dwelling, cognitively intact, and functionally independent older adults. Muscle strength, physical performance measures, cognitive tests and nutritional assessments were performed. Short Physical Performance Battery (SPPB) was administered at baseline and at 2 years. We compared HGSave and HGSmax to assess the prevalence of low HGS and sarcopenia. Univariate analysis was performed comparing baseline characteristics between low and normal groups for each HGS criterion. Significantly different variables were included in logistic regression analysis to examine association of low HGS and SPPB at baseline. Predictive validity of low HGS for SPPB<10 at 2 years was examined by performing logistic regression analysis for HGSave and HGSmax. RESULTS: The prevalence of low HGS and sarcopenia incorporating HGSave criterion is 40% and 33% respectively, whereas that of HGSmax criterion is 21% and 19.5% respectively. There is moderate agreement between the 2 HGS criteria for sarcopenia diagnosis (kappa=0.604) and poorer agreement for low HGS (kappa=0.570). There was no significant association with baseline SPPB for both HGS criteria. At 2 years, only low HGSmax was significantly associated with low SPPB (adjusted OR 3.91, 95% CI 1.24 - 12.33). CONCLUSION: Our study demonstrates that HGS criteria matters in diagnosis of sarcopenia and we support extant HGS protocols using HGSmax criterion in view of better predictive validity for poor physical performance.

Obesity Definitions in Sarcopenic Obesity: Differences in Prevalence, Agreement and Association with Muscle Function.

BACKGROUND: Sarcopenic obesity (SO) is associated with poorer physical performance in the elderly and will increase in relevance with population ageing and the obesity epidemic. The lack of a consensus definition for SO has resulted in variability in its reported prevalence, poor inter-definitional agreement, and disagreement on its impact on physical performance, impeding further development in the field. While sarcopenia definitions have been compared, the impact of obesity definitions in SO has been less well-studied. OBJECTIVES: To compare 3 widely-adopted definitions of obesity in terms of SO prevalence, inter-definitional agreement, and association with muscle function. DESIGN: Cross-sectional. SETTING: GERILABS study, Singapore Participants: 200 community-dwelling, functionally-independent older adults. MEASUREMENTS: We utilized three commonly-used definitions of obesity: body mass index (BMI), waist circumference (WC) and DXA-derived fat mass percentage (FM%). Sarcopenia was defined using Asian Working Group for Sarcopenia criteria. For muscle function, we assessed handgrip strength, gait speed and Short Physical Performance Battery (SPPB). Subjects were classified into 4 body composition phenotypes (normal, obese, sarcopenic and SO), and outcomes were compared between groups. RESULTS: The prevalence rate for SO was lowest for BMI (0.5%) compared to FM% (10.0%) and WC (10.5%). Inter-definitional agreement was lowest between BMI and WC (κ=0.364), and at best moderate between FM% and WC (κ=0.583). SO performed the worst amongst body composition phenotypes in handgrip strength, gait speed and SPPB (all p<0.01) only when defined using WC. In regression analyses, SO was associated with decreased SPPB scores (ß=-0.261, p=0.001) only for the WC definition. CONCLUSION: There is large variation in the prevalence of SO across different obesity definitions, with low-to-moderate agreement between them. Our results corroborate recent evidence that WC, and thus central obesity, is best associated with poorer muscle function in SO. Thus, WC should be further explored in defining obesity for accurate and early characterization of SO among older adults in Asian populations.

Frailty Assessment in Community-Dwelling Older Adults: A Comparison of 3 Diagnostic Instruments.

OBJECTIVES: Compare the diagnostic performance of FRAIL against Fried Phenotype and Frailty Index (FI), and identify clinical factors associated with pre-frailty/frailty. DESIGN: Cross-sectional analysis. SETTING: Community-based screenings in Senior Activity Centres, Residents' Corners and Community Centres in northeast Singapore. PARTICIPANTS: 517 community dwelling participants aged >55 years and ambulant independently (with/ without walking aids) were included in this study. Residents of sheltered or nursing homes, and seniors unable to ambulate at least four meters independently were excluded. MEASUREMENTS: The multidomain geriatric screen included assessments for social vulnerability, mood, cognition, sarcopenia and nutrition. Participants completed a battery of physical fitness tests for grip strength, gait speed, lower limb strength and power, flexibility, balance and endurance, with overall physical performance represented by Short Physical Performance Battery (SPPB). Frailty status was assigned on FRAIL, Fried and 35-item FI. RESULTS: Prevalence of frailty was 1.3% (FRAIL) to 3.1% (FI). Pre-frailty prevalence ranged from 17.0% (FRAIL) to 51.2% (FI). FRAIL demonstrated poor agreement with FI (kappa=0.171, p<0.0001), and Fried (kappa=0.194, p<0.0001). A lower FRAIL cut-off ≥1 yielded significantly improved AUC of 0.70 (95%CI 0.55 to 0.86, p=0.009) against Fried, and 0.71 (95%CI 0.55 to 0.86, p=0.008) against FI. All 3 frailty measures were diagnostic of impaired physical performance on SPPB, with AUCs ranging from 0.69 on FRAIL to 0.77 on Fried (all p values <0.01). Prevalence of low socio-economic status, depression, malnutrition and sarcopenia increased significantly, while fitness measures of gait speed, balance, and endurance declined progressively across robust, pre-frail and frail on all 3 frailty instruments (p <0.05). CONCLUSIONS: Our results suggest that different frailty instruments may capture over-lapping albeit distinct constructs, and thus may not be used interchangeably. FRAIL has utility for quick screening, and any positive response should trigger further assessment, including evaluation for depression, social vulnerability and malnutrition.

Serum Myostatin and IGF-1 as Gender-Specific Biomarkers of Frailty and Low Muscle Mass in Community-Dwelling Older Adults.

OBJECTIVES: (i) To investigate serum myostatin (absolute and normalized for total body lean mass (TBLM)) and IGF-1 as biomarkers of frailty and low relative appendicular skeletal muscle mass (RASM) in older adults, and; (ii) to examine gender differences in the association of serum myostatin and IGF-1 levels with frailty and low RASM. DESIGN: Cross-sectional study. SETTING: The "Longitudinal Assessment of Biomarkers for characterization of early Sarcopenia and predicting frailty and functional decline in community-dwelling Asian older adults Study" (GERI-LABS) study in Singapore. PARTICIPANTS: 200 subjects aged 50 years and older residing in the community. MEASUREMENTS: Frailty was assessed using the modified Fried criteria. Low RASM was defined using cutoffs for height-adjusted appendicular skeletal muscle mass measured by dual-energy X-ray absorptiometry as recommended by the Asian Working Group for Sarcopenia. Comorbidities, cognitive and functional performance, physical activity and nutritional status were assessed. Blood samples collected included serum myostatin, insulin-like growth factor 1 (IGF-1) and markers of inflammation (total white cell count, CRP, IL-6 and TNFaR1). Subjects were classified into 4 groups: Frail/Prefrail with low RASM (Frail/Low RASM), Frail/Prefrail with normal RASM (Frail/Normal RASM), Robust with low RASM (Robust/Low RASM) and Robust with normal RASM (Robust/Normal RASM). RESULTS: 63 (32%) subjects were classified as Frail/Low RASM, 53 (27%) Frail/Normal RASM, 28 (14%) Robust/Low RASM and 56 (28%) Robust/Normal RASM respectively. Frail/Low RASM subjects were older and had lower BMI compared to Frail/Normal RASM and robust subjects. Mean (SE) normalized myostatin levels were higher in Frail/Low RASM compared to Frail/Normal RASM subjects (1.0 (0.04) versus 0.84 (0.05) ng/ml/kg, P=0.01). Median (IQR) IGF-1 level was lower amongst Frail/Low RASM subjects compared to Frail/Normal RASM subjects (102.3, (77.7, 102.5) vs 119.7 (82.7, 146.0) ng/ml, P=0.046). No differences in myostatin or IGF-1 were observed among robust individuals with or without low muscle mass. In adjusted multinomial logistic regression models with Robust/Normal RASM as the reference group, myostatin (P=0.05) and IGF-1 (P=0.043) were associated with Frail/Low RASM status in the whole cohort. When stratified by gender, myostatin was significantly associated with Frail/Low RASM status in men only (P=0.03). In women, serum IGF-1 was associated with Frail/Low RASM status (P=0.046), but not myostatin (P=0.53). CONCLUSION: Serum myostatin, normalized for TBLM in men and IGF-1 in women are potential biomarkers for frail individuals with low RASM, and may identify a target group for intervention.

Association of nutrition and immune-endocrine dysfunction with muscle mass and performance in cognitively impaired older adults.

BACKGROUND: With lean mass declining early in Alzheimer's disease, muscle quality beyond quantity is relevant to physical performance. We sought to identify potentially modifiable factors for the differential loss of muscle mass (pre-sarcopenia) and its performance (sarcopenia) in older adults with mild cognitive impairment (MCI) and mild-to-moderate Alzheimer's disease (AD). METHODS: This is a cross-sectional study of 108 community-dwelling older adults with MCI and mild-to-moderate AD. Participants were categorized as: (i) No sarcopenia (normal muscle mass), (ii) Pre-sarcopenia (low muscle mass without weakness or slowness), (iii) Sarcopenia (low muscle mass AND weak grip strength and/or slow gait speed) using Asian cut-offs. Muscle quality was defined as the ratio of grip and knee extension strength to average arm and leg lean mass respectively. We measured cognitive, functional and physical (Short Physical Performance Battery, SPPB) performance; physical activity level; nutritional status; and blood biomarkers of inflammation and endocrine dysfunction. RESULTS: SPPB (p=0.033) and activity level (p=0.010) were highest in the pre-sarcopenic group. Pre-sarcopenic group had highest arm muscle quality [10.6 (7.7-12.2) vs 13.9 (12.6-15.7) vs 11.3 (9.7-12.8), p<0.001], despite significantly lower appendicular lean mass than non-sarcopenic group. In multi-nomial logistic regression reference to non-sarcopenic group, malnutrition independently increased risk for both pre-sarcopenia (Relative risk=7.53, 95% C.I 1.20-47.51, p=0.032) and sarcopenia (Relative risk=11.91, 95% C.I 2.85-49.77, p=0.001). A combined pro-inflammatory and endocrine deficient state significantly increased the risk of sarcopenia (Relative risk=5.17, 95% C.I 1.31-20.37, p=0.019). CONCLUSION: Malnutrition is a precursor for progressive loss of muscle mass, but a pro-inflammatory and endocrine deficient state may potentially aggravate decline in muscle quality to culminate in frank sarcopenia.

Analysis of Phosphatidic Acid Binding and Regulation of PIPKI In Vitro and in Intact Cells.

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a lipid second messenger that regulates a wide array of essential cellular events, such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, adhesion, and motility. To control the spatiotemporal production of PI(4,5)P2, the activity of type 1 phosphotidylinositol-4-phosphate-5-kinases (PIPKIs) is tightly regulated by small GTPases and another signaling lipid, phosphatidic acid (PA). It is of interest that PI(4,5)P2 is also a critical cofactor for the activation of the PA-generating enzyme, phospholipase D (PLD). It has been proposed that the reciprocal stimulation of PLD and PIPKI enzymes enables a rapid feedforward stimulation loop for the localized and acute generation of signaling lipids that are critical for the regulation of actin cytoskeletal reorganization and membrane trafficking. Here, we outline the methods for the expression and purification of PIPKIγ from bacteria, determination of direct PA binding, and activation of PIPKIγ using in vitro liposomes assays, and examination of actin cytoskeletal reorganization promoted by the PA-PIPKIγ signaling in intact cells using fluorescent microscopy.

7,12-dimethylbenz[a]anthracene-induced DNA binding and repair synthesis in susceptible and nonsusceptible mammary epithelial cells in culture.

The effect of age and parity on the binding of 7,12-dimethybenz[a]anthracene (DMBA) to DNA and the repair of DMBA-damaged DNA have been demonstrated in logarithmic phase and confluent mammary epithelial cell cultures from young virgin (YV), old virgin (OV), and parous (P) noninbred and inbred Sprague-Dawley rats. Over a dose range of 0.1-0.4 micrograms DMBA/ml, DNA binding was 1.5-to 2.0-fold higher in YV cells than in OV or P cells. In addition, a steeper slope of the dose-response curve was obtained with YV cells, suggesting a greater susceptibility of YV cells to DMBA. Excision repair was determined by measuring, in the presence of hydroxyurea and 5-bromodeoxyuridine, tritiated thymidine incorporation into DNA during the repair process. At high doses od DMBA (0.5-2.0 micrograms/ml), excision repair in YV cells was 1.5 times higher than in OV cells and 2 times higher than in P cells. However, with lower DMBA doses (less than 0.5 micrograms/ml) similar levels of repair were obtained in all 3 groups of rats. Since binding to DNA is higher in YV cells at these low DMBA doses, ti is apparent that OV and P cells exhibit a greater DNA repair per unit damage. These results, therefore, suggest that age and parity not only lower the binding of DMBA to mammary epithelial cell DNA but also increase the efficiency of DNA repair processes, which may explain the lower susceptibility of OV and P rats to DMBA-induced mammary carcinogenesis.