High throughput volatile fatty acid skin metabolite profiling by thermal desorption secondary electrospray ionisation mass spectrometry.

The non-invasive nature of volatile organic compound (VOC) sampling from skin makes this a priority in the development of new screening and diagnostic assays. Evaluation of recent literature highlights the tension between the analytical utility of ambient ionisation approaches for skin profiling and the practicality of undertaking larger campaigns (higher statistical power), or undertaking research in remote locations. This study describes how VOC may be sampled from skin and recovered from a polydimethylsilicone sampling coupon and analysed by thermal desorption (TD) interfaced to secondary electrospray ionisation (SESI) time-of-flight mass spectrometry (MS) for the high throughput screening of volatile fatty acids (VFAs) from human skin. Analysis times were reduced by 79% compared to gas chromatography-mass spectrometry methods (GC-MS) and limits of detection in the range 300 to 900 pg cm(-2) for VFA skin concentrations were obtained. Using body odour as a surrogate model for clinical testing 10 Filipino participants, 5 high and 5 low odour, were sampled in Manilla and the samples returned to the UK and screened by TD-SESI-MS and TD-GC-MS for malodour precursors with greater than >95% agreement between the two analytical techniques. Eight additional VFAs were also identified by both techniques with chains 4 to 15 carbons long being observed. TD-SESI-MS appears to have significant potential for the high throughput targeted screening of volatile biomarkers in human skin.

Gas-phase and solution studies of three resorcin[4]arene derivatives using electrospray time-of-flight mass spectrometry.

Electrospray ionisation mass spectrometry (ESI-MS) has been used to study the relative gas-phase proton and alkali metal (Li, Na, K and Cs) binding affinities of three different resorcin[4]arenes using the kinetic method. Collision-induced dissociation (CID) was used to study the fragmentation of resorcin[4]arene heterodimer sandwich complexes, allowing the relative binding affinity order to be established. All the alkali metal cations have the same gas-phase binding affinity order with the resorcin[4]arene host molecules. At collision energies of > or = 13eV, one of the [resorcin[4]arene+Metal]+, (Metal = Li, Na, K) ions fragmented through break-up of the resorcin[4]arene, whilst the other host resorcin[4]arene remained intact, causing an apparent change in binding affinity at high collision energy. This effect was not observed with caesium, since all complex ions dissociated readily under CID by displacement of the caesium cation. The binding affinity for the protonated resorcin[4]arenes was found to be different from the alkali metal cation binding affinity because of the higher proton affinity of the nitrogen-containing resorcin[4]arenes. It is shown that resorcin[4]arenes containing an oxazine ring can be converted into a ring-opened derivative via an Eschweiler-CLarke reaction in the presence of formic acid. A second ring-opening process also occurs, including a hydrolysis reaction that results in apparent Losses of 12 mass units from the intact resorcin[4]arene. Both these reactions occur in solution before mass spectrometric investigation and cannot be achieved by CID. This observation was confirmed by inducing the Eschweiter-CLarke reaction in a model benzoxazine compound.

Age-associated changes in hand grip and quadriceps muscle strength ratios in healthy adults.

BACKGROUND AND AIMS: Muscle strength may decline with age differentially in the upper and lower limbs. This information is difficult to capture through a single measure. The present study therefore aimed to characterize the relative changes in handgrip and lower limb muscle strength with aging by expressing them as a ratio. METHODS: Thirty-eight healthy volunteers aged 20-82 years performed maximal voluntary contractions (MVC) of quadriceps and handgrip using a custom-built transducer and a Jamar dynamometer respectively. RESULTS: The grip-quadriceps ratios for young adults was similar in males and females (0.75); indicating knee extensor force exceeded grip force by approximately 25%. Ratios were increased in older adults (p=0.05), and strength of the two muscle groups was approximately equal (1.1). Pearson's correlation coefficients for grip against quadriceps strength were r=0.63 (young males), r=0.83 (young females), r=0.35 (older males) and r=0.05 (older females). CONCLUSIONS: The ratio used demonstrated clear differences between the age groups. The reduced muscle strength with increasing age was expected, but the higher grip/quadriceps strength ratios quantify a greater loss of quadriceps than grip strength with aging. It remains to be investigated whether the relatively greater rate of decline in quadriceps strength seen in healthy older people is more exaggerated in those who are frail, which would have implications for using grip strength as a physical marker of lower limb strength and function in those at risk of immobility and falls.

Sampling and characterisation of volatile organic compound profiles in human saliva using a polydimethylsiloxane coupon placed within the oral cavity.

Evaluation of published methods reveals that existing methods for saliva sampling do not address the physical-chemical attributes of volatile organic compounds (VOCs). This study describes and presents evidence for adopting in situ sampling of salivary VOCs directly from the oral cavity using a polydimethylsiloxane (PDMS) based sampler. In vitro studies indicated that the vapour pressure of analytes was a factor in both the recovery of analytes and the precision of the recovery. The highest recoveries were observed for VOCs with the lowest vapour pressures, for example 5-nonanol (vapour pressure (P(v)) = 14 Pa) recoveries were approximately 20 times greater than those observed for octane (P(v) = 1726 Pa). Similarly, relative standard deviations reduced with vapour pressure, with the RSD for 5-nonanol responses observed to be 2.7% when compared to RSD = 26% for octane. Evaluation of VOCs recovered from 6 in vivo samples indicated that VOC concentrations in saliva may follow log-normal distributions; log-normal RSDs falling between 4.4% and 18.2% across the range of volatilities encountered. Increasing sampling time from 1 to 30 minutes indicated that the recovery of VOC into the sampler was affected by interaction between different physical-chemical properties and biogenic flux. A sampling time of 10 min was found to offer an acceptable compromise that enabled a representative sample to be acquired for the widest range of observed VOC behaviours with the sampler. The potential to 'tune' the sampling protocol for targeted analysis based on these factors was also noted. Comparison with passive drool saliva collection revealed up to 10(5) enhancement with reduced variability compared to drooled samples. This approach to in situ saliva sampling appears to have significant analytical utility for studying volatile signatures in humans.

A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach.

BACKGROUND: the European Working Group on Sarcopenia in Older People has developed a clinical definition of sarcopenia based on low muscle mass and reduced muscle function (strength or performance). Grip strength is recommended as a good simple measure of muscle strength when 'measured in standard conditions'. However, standard conditions remain to be defined. METHODS: a literature search was conducted to review articles describing the measurement of grip strength listed in Medline, Web of Science and Cochrane Library databases up to 31 December 2009. RESULTS: there is wide variability in the choice of equipment and protocol for measuring grip strength. The Jamar hand dynamometer is the most widely used instrument with established test-retest, inter-rater and intra-rater reliability. However, there is considerable variation in how it is used and studies often provide insufficient information on the protocol followed making comparisons difficult. There is evidence that variation in approach can affect the values recorded. Furthermore, reported summary measures of grip strength vary widely including maximum or mean value, from one, two or three attempts, with either hand or the dominant hand alone. CONCLUSIONS: there is considerable variation in current methods of assessing grip strength which makes comparison between studies difficult. A standardised method would enable more consistent measurement of grip strength and better assessment of sarcopenia. Our approach is described.

A systematic review of the use of volunteers to improve mealtime care of adult patients or residents in institutional settings.

AIMS AND OBJECTIVES: The objective of this review was to locate and assess the evidence obtained from articles reporting empirical research that volunteers improve mealtime care of adults in institutional settings. BACKGROUND: Malnutrition in adult patients or residents in institutional care settings is common. Poor standards of mealtime care have been suggested to contribute to the development of malnutrition. DESIGN: A systematic review of the literature was undertaken. METHOD: Key words were identified and used separately and in combination to search the electronic databases MEDLINE, CINHAL, BNI and EMBASE and the internet for relevant articles. Searches were undertaken in August 2008, April 2009 and July 1010. RESULTS: Ten studies fulfilled the criteria for inclusion. The methodologies of five of the 10 studies were unclear due to the brevity of the reports. The validity of the design of the other five studies varied. Generally the results suggested the use of volunteers in mealtime care increased satisfaction of patients, relatives, volunteers and staff concerning meal-time assistance (assessed using methods such as questionnaires and focus groups) and three studies found increased nutritional intake in groups assisted by volunteers. However, few well designed and reported studies were identified. CONCLUSIONS: There is some evidence that volunteers can improve mealtime care of adult patients or residents in institutional settings, however few well designed studies are reported. Relevance to clinical practice. This review demonstrates that there is limited evidence that the use of volunteers improves mealtime care of adult patients or relatives in institutional settings.

Hertfordshire sarcopenia study: design and methods.

BACKGROUND: Sarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms. METHODS: One hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study. DISCUSSION: The novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia.

Randomized controlled trial of the efficacy of aerobic exercise in reducing metabolic risk in healthy older people: The Hertfordshire Physical Activity Trial.

BACKGROUND: While there are compelling observational data confirming that individuals who exercise are healthier, the efficacy of aerobic exercise interventions to reduce metabolic risk and improve insulin sensitivity in older people has not been fully elucidated. Furthermore, while low birth weight has been shown to predict adverse health outcomes later in life, its influence on the response to aerobic exercise is unknown. Our primary objective is to assess the efficacy of a fully supervised twelve week aerobic exercise intervention in reducing clustered metabolic risk in healthy older adults. A secondary objective is to determine the influence of low birth weight on the response to exercise in this group. METHODS/DESIGN: We aim to recruit 100 participants born between 1931-1939, from the Hertfordshire Cohort Study and randomly assign them to no intervention or to 36 fully supervised one hour sessions on a cycle ergometer, over twelve weeks. Each participant will undergo detailed anthropometric and metabolic assessment pre- and post-intervention, including muscle biopsy, magnetic resonance imaging and spectroscopy, objective measurement of physical activity and sub-maximal fitness testing. DISCUSSION: Given the extensive phenotypic characterization, this study will provide valuable insights into the mechanisms underlying the beneficial effects of aerobic exercise as well as the efficacy, feasibility and safety of such interventions in this age group. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN60986572.

The developmental origins of sarcopenia: using peripheral quantitative computed tomography to assess muscle size in older people.

BACKGROUND: A number of studies have shown strong graded positive relationships between size at birth, grip strength, and estimates of muscle mass in older people. However no studies to date have included direct measures of muscle size. METHODS: We studied 313 men and 318 women born in Hertfordshire, United Kingdom between 1931 and 1939 who were still resident there and had historical records of growth in early life. Information on lifestyle was collected, and participants underwent peripheral quantitative computed tomography to directly measure forearm and calf muscle size. RESULTS: Birth weight was positively related to forearm muscle area in the men (r = 0.24, p <.0001) and women (r = 0.17, p =.003). There were similar but weaker associations between birth weight and calf muscle area in the men (r = 0.13, p =.03) and in the women (r = 0.17, p =.004). These relationships were all attenuated by adjustment for adult size. CONCLUSION: We present first evidence that directly measured muscle size in older men and women is associated with size at birth. This may reflect tracking of muscle size and is important because it suggests that benefit may be gained from taking a life course approach both to understanding the etiology of sarcopenia and to developing effective interventions.

Diet and its relationship with grip strength in community-dwelling older men and women: the Hertfordshire cohort study.

OBJECTIVES: To examine relationships between diet and grip strength in older men and women and to determine whether prenatal growth modifies these relationships. DESIGN: Cross-sectional and retrospective cohort study. SETTING: Hertfordshire, United Kingdom. PARTICIPANTS: Two thousand nine hundred eighty-three men and women aged 59 to 73 who were born and still living in Hertfordshire, United Kingdom. MEASUREMENTS: Weight at birth recorded in Health Visitor ledgers; current food and nutrient intake assessed using an administered food frequency questionnaire; and grip strength measured using a handheld dynamometer. RESULTS: Grip strength was positively associated with height and weight at birth and inversely related to age (all P<.001). Of the dietary factors considered in relation to grip strength, the most important was fatty fish consumption. An increase in grip strength of 0.43 kg (95% confidence interval (CI)=0.13-0.74) in men (P=.005) and 0.48 kg (95% CI=0.24-0.72) in women (P<.001) was observed for each additional portion of fatty fish consumed per week. These relationships were independent of adult height, age, and birth weight, each of which had additive effects on grip strength. There was no evidence of interactive effects of weight at birth and adult diet on grip strength. CONCLUSION: These data suggest that fatty fish consumption can have an important influence on muscle function in older men and women. This raises the possibility that the antiinflammatory actions of omega-3 fatty acids may play a role in the prevention of sarcopenia.

Falls, sarcopenia, and growth in early life: findings from the Hertfordshire cohort study.

Recent studies have shown that people whose early growth is poor have an increased risk of sarcopenia. Sarcopenia is an important risk factor for falls, but it is not known whether poor early growth is related to falls. The authors investigated this association in the Hertfordshire Cohort Study (1998-2004), where 2,148 participants from the United Kingdom provided their history of falls. Grip strength was used as a marker of sarcopenia. Birth weight, weight at 1 year, and conditional infant growth were analyzed in relation to history of falls. The prevalence of any fall in the last year was 14.3% for men and 22.5% for women. Falls in the last year were inversely related to adult grip strength, height, and walking speed in men and women as well as to lower conditional infant growth in men (odds ratio = 1.27, 95% confidence interval: 1.04, 1.56 per standard deviation decrease in conditional infant growth; p = 0.02). This association was attenuated after adjustment for grip strength. These findings support an association between poor early growth and falls in older men that appears to be mediated partly through sarcopenia. The lack of a relation with birth weight suggests that postnatal rather than prenatal influences on muscle growth and development may be important regarding the risk of falls in later life.

Combined effects of dietary fat and birth weight on serum cholesterol concentrations: the Hertfordshire Cohort Study.

BACKGROUND: Blood cholesterol responses to the manipulation of dietary fat vary widely between persons. Although epidemiologic evidence suggests that prenatal growth and nutrition influence adult cholesterol homeostasis, whether prenatal growth modifies the association between dietary fat intake and serum cholesterol concentration in adults is unknown. OBJECTIVE: The aim was to examine the relation between fat intake and serum cholesterol concentrations in men and women whose birth weights were known. DESIGN: We studied a cohort of men and women aged 59-71 y. Diet was assessed with a food-frequency questionnaire. Total, HDL-, and LDL-cholesterol concentrations and the ratio of HDL to LDL cholesterol were measured in fasting blood samples from 574 men and 562 women who did not have coronary heart disease. RESULTS: Total and saturated fat intakes were not associated with serum cholesterol concentrations in men or women. However, subdivision by birth weight showed associations in men but not in women. High intakes of total and saturated fat were associated with reduced HDL-cholesterol concentrations in men with birth weights < or =3.2 kg (7 lb) but not in men with higher birth weights. Similar effects on the HDL-to-LDL cholesterol ratio were observed (P for interaction = 0.02 for total fat and 0.01 for saturated fat). When 32 men taking cholesterol-lowering medication were excluded, the interactions were strengthened (P = 0.008 and 0.006, respectively). CONCLUSION: The adverse effects of high intakes of total and saturated fat on serum cholesterol concentrations in men may be confined to those with lower birth weights.

Is grip strength associated with health-related quality of life? Findings from the Hertfordshire Cohort Study.

OBJECTIVE: to investigate the relationship between grip strength and health-related quality of life (HRQoL). DESIGN: cross-sectional survey within a cohort study design. SETTING: the county of Hertfordshire in the UK. PARTICIPANTS: a total of 2,987 community-dwelling men and women aged 59-73 years of age. MEASUREMENTS: grip strength was used as a marker of sarcopaenia and measured using a Jamar dynamometer. HRQoL was assessed using the eight domain scores of the Short Form-36 (SF-36) questionnaire, and subjects in the lowest sex-specific fifth of the distribution were classified as having 'poor' status for each domain. RESULTS: men and women with lower grip strength were significantly more likely to report a poor as opposed to excellent to fair overall opinion of their general health (GH) [odds ratio (OR) per kilogram decrease in grip strength = 1.13, 95% CI = 1.06-1.19, P < 0.001 in men, 1.13, 95% CI = 1.07-1.20, P < 0.001 in women]. Among men, after adjustment for age, size, physical activity and known co-morbidity, decreased grip strength was associated with increased prevalence of poor SF-36 scores for the physical functioning (PF) (OR per kilogram decrease in grip strength = 1.03, 95% CI = 1.01-1.06, P = 0.007) and GH domains (OR = 1.03, 95% CI = 1.01-1.05, P = 0.01). Similar associations were seen in women. CONCLUSIONS: our findings suggest that lower grip strength is associated with reduced HRQoL in older men and women. This does not appear to be explained by age, size, physical activity or co-morbidity and may reflect the link between sarcopaenia and generalised frailty. Individuals with sarcopaenia may benefit from interventions to improve muscle mass and strength before the onset of chronic disorders usually associated with impaired HRQoL.