Effects of once- versus twice-weekly eccentric resistance training on muscular function and structure in older adults: a randomised controlled trial.

Adherence rates to current twice-weekly strength training guidelines are poor among older adults. Eccentric-only training elicits substantial improvements in muscle function/size so the aim of this study was to compare the effects of once- versus twice-weekly eccentric training programmes on muscle function/size in older adults. Thirty-six participants (69.4 ± 6.0 yr) were randomised into non-active control, once-, or twice-weekly training groups. Lower-limb muscle power, strength, and size were assessed at baseline, mid-, and post-eccentric training. Training was performed for 12 min per session at 50% of maximum eccentric strength. Significant increases in power (13%), isometric (17-36%) and eccentric (40-50%) strength, and VL muscle thickness (9-18%) occurred in both training groups following 12 weeks. Minimal muscle soreness was induced throughout the 12 weeks and perceived exertion was consistently lower in the twice-weekly training group. One weekly submaximal eccentric resistance training session over 12 weeks elicits similar improvements in neuromuscular function compared to the currently recommended twice-weekly training dose. Given the substantial improvements in neuromuscular function and previously reported low adherence to current twice-weekly training guidelines, eccentric training may be pivotal to developing a minimal-dose strategy to counteract neuromuscular decline. The trial was registered retrospectively on 24/01/2024 with ISRCTN (trial registration number: ISRCTN68730580).

Epigenetic MLH1 silencing concurs with mismatch repair deficiency in sporadic, naturally occurring colorectal cancer in rhesus macaques.

BACKGROUND: Naturally occurring colorectal cancers (CRC) in rhesus macaques share many features with their human counterparts and are useful models for cancer immunotherapy; but mechanistic data are lacking regarding the comparative molecular pathogenesis of these cancers. METHODS: We conducted state-of-the-art imaging including CT and PET, clinical assessments, and pathological review of 24 rhesus macaques with naturally occurring CRC. Additionally, we molecularly characterized these tumors utilizing immunohistochemistry (IHC), microsatellite instability assays, DNAseq, transcriptomics, and developed a DNA methylation-specific qPCR assay for MLH1, CACNA1G, CDKN2A, CRABP1, and NEUROG1, human markers for CpG island methylator phenotype (CIMP). We furthermore employed Monte-Carlo simulations to in-silico model alterations in DNA topology in transcription-factor binding site-rich promoter regions upon experimentally demonstrated DNA methylation. RESULTS: Similar cancer histology, progression patterns, and co-morbidities could be observed in rhesus as reported for human CRC patients. IHC identified loss of MLH1 and PMS2 in all cases, with functional microsatellite instability. DNA sequencing revealed the close genetic relatedness to human CRCs, including a similar mutational signature, chromosomal instability, and functionally-relevant mutations affecting KRAS (G12D), TP53 (R175H, R273*), APC, AMER1, ALK, and ARID1A. Interestingly, MLH1 mutations were rarely identified on a somatic or germline level. Transcriptomics not only corroborated the similarities of rhesus and human CRCs, but also demonstrated the significant downregulation of MLH1 but not MSH2, MSH6, or PMS2 in rhesus CRCs. Methylation-specific qPCR suggested CIMP-positivity in 9/16 rhesus CRCs, but all 16/16 exhibited significant MLH1 promoter hypermethylation. DNA hypermethylation was modelled to affect DNA topology, particularly propeller twist and roll profiles. Modelling the DNA topology of a transcription factor binding motif (TFAP2A) in the MLH1 promoter that overlapped with a methylation-specific probe, we observed significant differences in DNA topology upon experimentally shown DNA methylation. This suggests a role of transcription factor binding interference in epigenetic silencing of MLH1 in rhesus CRCs. CONCLUSIONS: These data indicate that epigenetic silencing suppresses MLH1 transcription, induces the loss of MLH1 protein, abrogates mismatch repair, and drives genomic instability in naturally occurring CRC in rhesus macaques. We consider this spontaneous, uninduced CRC in immunocompetent, treatment-naïve rhesus macaques to be a uniquely informative model for human CRC.

Delapré Walk project: Are signposted walking routes an effective intervention to increase engagement in urban parks? -Natural experimental study.

Spatial education interventions in the built environment may increase engagement with urban greenspace. This research was a natural experimental study with mixed-method evaluation and repeated cross-sectional design. Twenty-four directional wayfinding signs were installed within an urban park to create a 3 km signposted walking route through the park's amenities in a clockwise direction. Manual counts on one path and bi-directional automated active infrared counts on six paths along the intervention route were conducted at baseline and 12-month follow-up. A QR code accessed intercept survey was open throughout the follow-up phase to capture user experiences, views, and attitudes toward the intervention. There was no consistent difference in manual counts at baseline or 12-month follow-up between intervention and control parks. Automated counts showed no consistent significant change in clockwise footfall between baseline (median automated count range across six counters: 10-130 clockwise counts per day) and follow-up (Autumn to Winter follow-up median automated count range across six counters: 13-103 clockwise counts per day; Spring to Summer follow-up median automated count range across six counters: 13-124 clockwise counts per day). However, 23% (11 out of 48 people) of clockwise travelling route users reported they were following the signs at 12-month follow-up. Intercept survey respondents (n = 27) appeared to be infrequent park users (number of respondents for 'my first visit': 7, and 'one to two times per month: 9), with the new signs making them feel less anxious about exploring unfamiliar areas, while motivating them to walk further than originally planned and helping them to 'take notice' of the landscape. Directional wayfinding for recreational walking appears to help infrequent users engage with urban greenspace.

The acute and repeated bout effects of multi-joint eccentric exercise on physical function and balance in older adults.

PURPOSE: Eccentric muscle actions generate high levels of force at a low metabolic cost, making them a suitable training modality to combat age-related neuromuscular decline. The temporary muscle soreness associated with high intensity eccentric contractions may explain their limited use in clinical exercise prescription, however any discomfort is often alleviated after the initial bout (repeated bout effect). Therefore, the aims of the present study were to examine the acute and repeated bout effects of eccentric contractions on neuromuscular factors associated with the risk of falling in older adults. METHODS: Balance, functional ability [timed up-and-go and sit-to-stand], and lower-limb maximal and explosive strength were measured in 13 participants (67.6 ± 4.9 year) pre- and post-eccentric exercise (0, 24, 48, and 72 hr) in Bout 1 and 14 days later in Bout 2. The eccentric exercise intervention was performed on an isokinetic unilateral stepper ergometer at 50% of maximal eccentric strength at 18 step‧min-1 per limb for 7 min (126 steps per limb). Two-way repeated measures ANOVAs were conducted to identify any significant effects (P ≤ 0.05). RESULTS: Eccentric strength significantly decreased (- 13%) in Bout 1 at 24 hr post-exercise; no significant reduction was observed at any other time-point after Bout 1. No significant reductions occurred in static balance or functional ability at any time-point in either bout. CONCLUSION: Submaximal multi-joint eccentric exercise results in minimal disruption to neuromuscular function associated with falls in older adults after the initial bout.

Clodronate detection and effects on markers of bone resorption are prolonged following a single administration to horses.

BACKGROUND: Clodronate is a potent antiresorptive agent labelled for use in horses over 4 years of age, for the treatment of navicular syndrome. Concerns regarding the extra-label use of clodronate in equine athletes, such as racehorses, have been raised as inhibition of osteoclast activity by clodronate has been postulated to interfere with normal bone healing, which is imperative to the repair of microfractures. The paucity of data describing the long-term pharmacokinetics of clodronate and effects on biomarkers of bone resorption necessitates further study. OBJECTIVES: (1) To determine clodronate concentrations in blood and urine over a 6-month period in horses undergoing treadmill exercise and (2) to assess the effects of clodronate on protein biomarkers of bone remodelling in this same group of horses. STUDY DESIGN: Randomised controlled experimental study. METHODS: Seven exercised Thoroughbred horses received a single im administration of 1.8 mg/kg clodronate and four horses received an equivalent volume of saline. Blood and urine samples were collected prior to, during and for 182 days post drug administration for drug concentration determination using liquid chromatography-tandem mass spectrometry, and determination of protein biomarker (CTX-1 and TRAcP5B) concentrations. RESULTS: Clodronate was detectable in blood for 14-175 days and for up to 175 days in urine. For some horses, concentrations were nondetectable at one time point but detectable at a subsequent time point. The terminal serum half-life ranged from 1.80 to 283.9 days. CTX-1 concentrations were significantly higher, relative to baseline, in both treated and control groups while concentrations of TRAcP5B were significantly lower in the treated group. MAIN LIMITATIONS: Relatively small number of horses studied. CONCLUSIONS: Based on assessment of protein biomarkers, clodronate appears to influence osteoclasts at label doses. Furthermore, results of this study support racing regulations that preclude horses administered bisphosphonates for medical reasons, from racing for a prolonged period of time.

CONTEXTO: Clodronato é um agente antirreabsortivo potente e recomendado para o uso em cavalos com mais de 4 anos de idade, para o tratamento da síndrome do navicular. Há preocupação com o uso indiscriminado de clodronato em equinos atletas, como cavalos de corrida, já que a inibição da atividade dos osteoclastos pelo clodronato tem sido postulada em interferir na cicatrização óssea normal, o que é essencial para a cicatrização de microfraturas. A escassez de informação quanto às ações prolongadas do uso de clodronato e seus efeitos nos biomarcadores de reabsorção óssea requere mais estudos. OBJETIVOS: (1) Determinar a concentração de clodronato no sangue e urina por um período de 6 meses em cavalos submetidos ao exercício em esteira e (2) acessar os efeitos de clodronato nos biomarcadores de remodelação óssea no mesmo grupo de cavalos. DELINEAMENTO DO ESTUDO: Estudo controlado randomizado. METODOLOGIA: Sete cavalos Puro-Sangue Inglês em exercício receberam uma única dose im de 1.8 mg/kg de clodronato e 4 cavalos receberam um volume equivalente de solução fisiológica. Amostras de sangue e urina foram coletadas antes, durante e por 182 dias após a administração de clodronato. Valores de concentração da droga foram determinados utilizando cromatografia líquida-espectrometria de massa (LC-MS/MS), e determinação da concentração de biomarcadores (CTX-1 e TRAcP5B) também foi realizada. RESULTADOS: Clodronato foi detectado no sangue por 14-175 dias e por até 175 dias na urina. Para alguns equinos, a concentração foi não-detectável em um momento, mas detectável no próximo momento. O valor terminal da vida-média em soro foi 1.80-283.9 dias. A concentração de CTX-1 foi significativamente elevada, relativo às amostras iniciais, em ambos os grupos (tratamento e controle), enquanto as concentrações de TRAcP5B foram significativamente menores no grupo de cavalos tratados. PRINCIPAIS LIMITAÇÕES: Número relativamente pequenos de cavalos no estudo. CONCLUSÕES: Baseado nos resultados dos biomarcadores, clodronato parece influencia osteoclastos na dose recomendada. Além disso, os resultados deste estudo suportam o regulamento de cavalos de corrida que impedem que cavalos que receberam bifosfonatos por razão médica de competir por um período de tempo prolongado.

COVID-19 and the long-term cardio-respiratory and metabolic health complications.

Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) transmission continues to impact people globally. Whilst the acute symptoms and management strategies are well documented, millions of people globally are experiencing a prolonged and debilitating symptom profile that is reported to last months and even years. COVID-19 is a multi-system disease however the magnitude of the effects and its associated legacy is presently not well understood. Early reports indicate that multidisciplinary approaches between clinical and non-clinical entities are needed to provide effective and rehabilitative patient support pathways and restore pre-COVID-19 quality of life and functional status. Accordingly, this review provides a summary of the impact on cardiovascular, inflammatory, respiratory, and musculoskeletal function following an acute COVID-19 infection along with the prolonged effects of long-COVID.

Influence of COVID-19 Building Restrictions on Physical Activity Promotion Through Increased Stair Use and Limited Elevator Access: A Quasi-Experimental Study-Sport and Physical Activity Group Active Campus Project.

BACKGROUND: The aim of this study was to determine the effectiveness of UK government COVID-19 safe offices policy to increase stair use in a higher education setting during the COVID-19 pandemic. METHODS: Automated counts at 3 ground floor staircases and the elevator entrances were used to estimate stair to elevator use ratio for ascent and descent from/to the ground floor of a university building at baseline (January to March 2020), first and second intervention months (October 2020, November 2020, respectively). Stair promoting signage and a 1-way system was implemented, in line with government policy. RESULTS: At baseline, stair to elevator use ratio for ascent from and descent to the ground floor was 1.36 (0.02) and 1.88 (0.02) people, respectively. The ratio significantly increased in the first intervention month to 2.64 (0.09) and 3.96 (0.22) people for ascent and descent, respectively. However, the ratio decreased between the first and second intervention months to 1.63 (0.06) and 3.05 (0.52) people for ascent and descent, respectively. CONCLUSION: The UK government COVID-19 policy was effective at increasing stair use in a higher education setting.

Pharmacokinetics and effects on arachidonic acid metabolism of low doses of cannabidiol following oral administration to horses.

The increasing availability of cannabidiol (CBD) and anecdotal reports of its anti-inflammatory effects has garnered it much interest in the equine industry. The objectives of the current study were to (1) describe the pharmacokinetics of oral CBD in exercising thoroughbreds, (2) characterize select behavioral and physiologic effects, and (3) evaluate effects on biomarkers of inflammation using an ex vivo model. This study was conducted in a randomized balanced 3-way crossover design with a two-week washout period between doses. Horses received a single oral dose (0.5, 1, and 2 mg/kg) of CBD suspended in sesame oil. Blood and urine samples were collected prior to and for 72 hr post drug administration. Additional blood samples collected at select time points were challenged ex vivo with calcium ionophore or lipopolysaccharide to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC-MS/MS. Cannabidiol was well tolerated with no significant behavioral, gastrointestinal, or cardiac abnormalities observed. CBD was readily absorbed, with parent drug detected in blood at all time points. The carboxylated and hydroxylated metabolites predominated in serum and urine, respectively. The terminal half-life for CBD was 10.7 ± 3.61, 10.6 ± 3.84 and 9.88 ± 3.53 for 0.5, 1, and 2 mg/kg. Although the effects were mixed, results of eicosanoid analysis suggest CBD affects COX-1, COX-2 and LOX at the doses studied here. Results of this study coupled with previous reports in other species, suggest further study of CBD in horses is warranted before its use as an anti-inflammatory can be recommended.

Correction to: The difference in sleep, sedentary behaviour, and physical activity between older adults with 'healthy' and 'unhealthy' cardiometabolic profiles: a cross-sectional compositional data analysis approach.

[This corrects the article DOI: 10.1186/s11556-019-0231-4.].

Using isotemporal substitution to predict the effects of changing physical behaviour on older adults' cardio-metabolic profiles.

BACKGROUND: It has been advocated that older adults should concomitantly spend less time in sedentary behaviour (SB), and engage in sufficient physical activity (PA), to reduce their risk of cardio-metabolic diseases. However, it is not clear what intensity of PA must be done to offset SB engagement. AIM: Model how cardio-metabolic profiles could change if older adults replaced an hour per day (hr·day-1) of a physical behaviour intensity with 1 hr·day-1 of another physical behaviour of a different intensity. METHODS: Older adults (n = 93, 60-89 years old, 55% female) wore a thigh-mounted triaxial accelerometer for seven consecutive free-living days to estimate mean daily hourly engagement in SB, Standing, Light Intensity PA (LIPA), sporadic moderate to vigorous physical activity (sMVPA, bouts <10 continuous minutes), and 10-minute MVPA (10MVPA, bouts ≥10 continuous minutes. Fasting whole blood concentration of plasma glucose, triglyceride, total cholesterol, and glycated haemoglobin (%), along with serum concentration of lipoprotein lipase (LPL), interleukin-6 (IL-6), and procollagen III N-terminal propeptide (PIIINP) were measured. RESULTS: Isotemporal Substitution, with covariate adjustment, suggested that: total cholesterol concentration could theoretically decrease when 1 hr·day-1 of SB is replaced with Standing, when 1 hr.day-1 of LIPA is replaced with Standing, and when 1 hr·day-1 of sMVPA is replaced with Standing. Triglyceride concentration theoretically decreased when 1 hr·day-1 of SB, Standing, LIPA, or sMVPA is replaced with 10MVPA. Triglyceride concentration theoretically increases when 1 hr·day-1 of 10MVPA is replaced with SB, Standing, or LIPA. No associations with time reallocation appears to exist for LPL, HbA1c, IL-6, and PIIINP. CONCLUSION: The type of physical behaviour being replaced could be crucial for total cholesterol maintenance. Engagement in 10MVPA could be necessary to improve triglyceride concentration.

Influence of Habitual Physical Behavior - Sleeping, Sedentarism, Physical Activity - On Bone Health in Community-Dwelling Older People.

Sedentary behavior (SB) has emerged as an independent public-health risk and may contribute to the lower bone mineral density (BMD) in old (>60 years of age) than young adults. The purpose of this study was to quantify SB and habitual physical behavior (PB) in community-dwelling older adults and how this correlates with BMD. In 112 relatively healthy and independent-living individuals aged 72.5 ± 6.4 years, BMD, PB and SB were determined using dual energy X-ray absorptiometry and 7-day three-dimensional accelerometry, respectively. In men, only healthy and osteopenic BMDs were found, whereas in women, osteoporotic BMD classifications also occurred. Our sample spent ∼61%, 7%, 12% and 19% of daily waking hours in SB, standing, LIPA [light intensity physical activity (PA)] and MVPA (medium-to-vigorous intensity PA), respectively. In men, after accounting for covariates (BMI, total fat, android:gynoid ratio), sleeping (hours/day), number of breaks in SB, number of SB ≥ 5 min, number of PA bouts, total duration of PA bouts (min), mean PA bouts duration (min), LIPA (%PA bout time) and MVPA (%PA bout time) were all predictors of BMD. In women, after accounting for covariates (age, BMI, total fat, android:gynoid ratio), SB (hours/day), SB (% waking hours), LIPA (hours/day), LIPA (% waking hours), MVPA (% waking hours) and number of short SB (i.e., <5 min), total time spent in PA (min) significantly correlated with BMD. In conclusion, the PB predictors of bone health in older persons include: night time sleeping duration, number of short bouts of SB, number and duration of bouts of PA relative to total waking hours. While radar graphs of PB patterns for healthy, osteopenic, osteoporotic individuals highlighted significant differences in PB between them, they were not consistent with the expectations from the Mechanostat Theory: i.e., more loading leads to better bone. Rather, our results suggest that a balance of activities must be maintained across the PB spectrum, where certain PB parameters are especially impactful in each sex, supporting the recently coined multifactorial-based variations in the Mechanostat threshold.

The difference in sleep, sedentary behaviour, and physical activity between older adults with 'healthy' and 'unhealthy' cardiometabolic profiles: a cross-sectional compositional data analysis approach.

BACKGROUND: Studies have seldom used Compositional Data Analysis (CoDA) to map the effects of sleep, sedentary behaviour, and physical activity on older adults' cardio-metabolic profiles. This study therefore aimed to illustrate how sleep, sedentary behaviour, and physical activity profiles differ between older adult groups (60-89 years), with 'low' compared to those with 'high' concentrations of endocrine cardio-metabolic disease risk markers, using CoDA. METHOD: Ninety-three participants (55% female) wore a thigh-mounted triaxial accelerometer for seven consecutive free-living days. Accelerometer estimates of daily average hours of engagement in sedentary behaviour (SB), standing, light-intensity physical activity (LIPA), sporadic moderate-vigorous physical activity (sMVPA, accumulated with bouts between 1 and 10 min), 10-min moderate-vigorous physical activity (10MVPA, accumulated with bouts ≥10 min), in addition to self-reported sleeping hours were reported. Fasted whole blood concentrations of total cholesterol, triglyceride, glucose, and glycated haemoglobin, and serum lipoprotein lipase (LPL), interleukin-6 (IL-6), and procollagen III N-terminal propeptide were determined. RESULTS: Triglyceride concentration appeared to be highly dependent on 10MVPA engagement as the 'low' and 'high' concentration groups engaged in 48% more and 32% less 10MVPA, respectively, relative to the geometric mean of the entire study sample. Time-use composition of the 'low' LPL group's engagement in 10MVPA was 26% less, while the 'high' LPL group was 7.9% more, than the entire study sample. Time-use composition of the 'high' glucose and glycated haemoglobin groups appeared to be similar as both engaged in more Sleep and SB, and less 10MVPA compared to the study sample. Participants with a 'low' IL-6 concentration engaged in 4.8% more Sleep and 2.7% less 10MVPA than the entire study sample. Time-use composition of the Total Cholesterol groups was mixed with the 'low' concentration group engaging in more Standing and 10MVPA but less Sleep, SB, LIPA, and sMVPA than the entire study sample. CONCLUSION: Older adults should aim to increase 10MVPA engagement to improve lipid profile and decrease SB engagement to improve glucose profile.

Reliability and validity of the international physical activity questionnaire compared to calibrated accelerometer cut-off points in the quantification of sedentary behaviour and physical activity in older adults.

BACKGROUND: The aim was to determine the reliability and validity of IPAQ measured sedentary behaviour (SB) and moderate-vigorous physical activity (MVPA) in older persons whilst examining any sex differences in reliability and validity results. METHOD: 89 participants (73.7 ± 6.3 years, 54% female) completed the IPAQ. Participants were fitted with a thigh mounted triaxial accelerometer (GeneActiv Original) for seven consecutive days and subsequently completed a second IPAQ. RESULTS: IPAQ showed weak reliability qualities for Total SB (h·week-1) and 10 minute MVPA (accumulated in bouts ≥ 10 continuous minutes, h·week-1). IPAQ had poor concurrent validity qualities for Total SB, 10 minute MVPA, but not Sporadic MVPA (accumulated in bouts < 10 continuous minutes, h·week-1). IPAQ only categorised participant physical behaviour classification correctly 2% of the time. Sex differences were only present for the correlation slope of IPAQ 10 minute MVPA reliability measures. CONCLUSION: Our data suggests that the IPAQ is not suitable for assessing older adults habitual physical behaviour.

Segregating the Distinct Effects of Sedentary Behavior and Physical Activity on Older Adults' Cardiovascular Profile: Part 2-Isotemporal Substitution Approach.

BACKGROUND: The aim of the study was to provide an isotemporal substitution model to predict how changes in physical behavior may affect the cardiovascular parameters (CVPs) of older adults. METHODS: Participants wore a thigh-mounted accelerometer for 7 days. Phenotype of the carotid, brachial, and popliteal artery was conducted using ultrasound. Isotemporal substitution was used to simulate the degree to which replacing 1 hour of physical behavior with another would affect CVP. RESULTS: Substitution of sedentary behavior with Standing and sporadic moderate- to vigorous-intensity physical activity (MVPA accumulated in bouts <10 min) would reduce resting heart rate [-6.20 beats per minute (-12.1 to -0.22) and -3.72 beats per minute (-7.01 to -0.44), respectively]. Substitution of sedentary behavior with light-intensity physical activity would reduce carotid artery diameter [-0.54 mm (-1.00 to -0.07)]. Substitution of Standing with sporadic MVPA would increase popliteal artery diameter [1.31 mm (0.11 to 2.51)]. CONCLUSIONS: Our modeling suggests that an accumulation of MVPA bouts that are shorter than the recommended 10-minute minimum may still improve CVP, with lower intensity physical activity also influencing CVP. Our findings are a promising avenue for lifestyle interventions in older adults to reduce the aging effects on CVP for those who cannot engage or sustain sufficient MVPA.

Segregating the Distinct Effects of Sedentary Behavior and Physical Activity on Older Adults' Cardiovascular Structure and Function: Part 1-Linear Regression Analysis Approach.

BACKGROUND: Physical behavior [PB, physical activity (PA), and sedentary behavior (SB)] can adjust cardiovascular mortality risk in older adults. The aim of this study was to predict cardiovascular parameters (CVPs) using 21 parameters of PB. METHODS: Participants [n = 93, 73.8 (6.23) y] wore a thigh-mounted accelerometer for 7 days. Phenotype of the carotid, brachial, and popliteal arteries was conducted using ultrasound. RESULTS: Sedentary behavior was associated with one of the 19 CVPs. Standing and light-intensity PA was associated with 3 and 1 CVP, respectively. Our prediction model suggested that an hourly increase in light-intensity PA would be negatively associated with popliteal intima-media thickness [0.09 mm (95% confidence interval, 0.15 to 0.03)]. sMVPA [moderate-vigorous PA (MVPA), accumulated in bouts <10 min] was associated with 1 CVP. 10MVPA (MVPA accumulated in bouts ≥10 min) had no associations. W50% had associations with 3 CVP. SB%, alpha, true mean PA bout, daily sum of PA bout time, and total week 10MVPA each were associated with 2 CVP. CONCLUSIONS: Patterns of PB are more robust predictors of CVP than PB (hours per day). The prediction that popliteal intima-media thickness would be negatively associated with increased standing and light-intensity PA engagement suggests that older adults could obtain health benefits without MVPA engagement.

Pumping-induced perturbation of flow in microfluidic channels and its implications for on-chip cell culture.

We study the rate of response to changes in the rate of flow and the perturbations in flow in polydimethylsiloxane (PDMS) microfluidic chips that are subjected to several common flow-control systems. We find that the flow rate of liquid delivered from a syringe pump equipped with a glass syringe responds faster to the changes in the conditions of flow than the same liquid delivered from a plastic syringe; and the rate of flow delivered from compressed air responds faster than that from a glass syringe. We discover that the rate of flow that is driven by a syringe pump and regulated by an integrated pneumatic valve responds even faster, but this flow-control method is characterized by large perturbations. We also examine the possible effects of these large perturbations on NIH 3T3 cells in microfluidic channels and find that they could cause the detachment of NIH 3T3 cells in the microchannels.

Single-cell assays.

This review presents an overview of literature that describes the applications of microfluidics to assay individual cells. We quantify the content of an individual mammalian cell, so that we can understand what criteria a single-cell assay must satisfy to be successful. We put in context the justification for single-cell assays and identify the characteristics that are relevant to single-cell assays. We review the literature from the past 24 months that describe the methods that use microfabrication-conventional or otherwise-and microfluidics in particular to study individual cells, and we present our views on how an increasing emphasis on three-dimensional cell culture and the demonstration of the first chemically defined cell might impact single-cell assays.

Fabrication of freestanding, microperforated membranes and their applications in microfluidics.

This manuscript describes a convenient method for the fabrication of freestanding, microperforated membranes in photocurable polymers using only one step of photolithography. We used photosensitive prepolymers to make the membranes and photolithography to define the micropatterns. We demonstrated the fabrication of single- and multilayer microperforated membranes in SU-8 photoresist and Norland Optical Adhesive prepolymer. These membranes can be used to pattern surfaces in various materials and to fabricate complex three-dimensional microfluidic channel structures.

Fabrication of a microfluidic Ag/AgCl reference electrode and its application for portable and disposable electrochemical microchips.

This report describes a convenient method for the fabrication of a miniaturized, reliable Ag/AgCl reference electrode with nanofluidic channels acting as a salt bridge that can be easily integrated into microfluidic chips. The Ag/AgCl reference electrode shows high stability with millivolt variations. We demonstrated the application of this reference electrode in a portable microfluidic chip that is connected to a USB-port microelectrochemical station and to a computer for data collection and analysis. The low fabrication cost of the chip with the potential for mass production makes it disposable and an excellent candidate for real-world analysis and measurement. We used the chip to quantitatively analyze the concentrations of heavy metal ions (Cd(2+) and Pb(2+)) in sea water. We believe that the Ag/AgCl reference microelectrode and the portable electrochemical system will be of interest to people in microfluidics, environmental science, clinical diagnostics, and food research.

Convenient method for modifying poly(dimethylsiloxane) to be airtight and resistive against absorption of small molecules.

In this paper we present a simple and rapid method of modifying poly(dimethylsiloxane) (PDMS) surfaces with paraffin wax. PDMS that contains a layer of paraffin wax at its surface resists the absorption of hydrophobic molecules; we used fluorescence microscopy to confirm that paraffin-modified PDMS resists the absorption of rhodamine B. Furthermore, we demonstrated that microfluidic devices made from PDMS that contains a surface layer of paraffin wax prevent efficiently the transport of gas molecules through the bulk and into microchannels. We characterized the surface of PDMS that contains paraffin wax using the water contact angle, optical transmission, and X-ray photoelectron spectroscopy. We show that PDMS that contains paraffin wax can be substituted for native PDMS; specifically, we fabricated peristaltic valves in PDMS that contains paraffin wax, and the valves showed no degradation in performance after multiple open/close cycles. Finally, we show how to use PDMS that has been treated with paraffin wax as a mold for the fabrication of PDMS replicas; this approach avoids silanization of PDMS, which is a time-consuming step in soft lithography. The wax-modified PDMS channels also show performance superiro to that of bare PDMS in micellar electrokinetic chromatography for quantitative analysis.