Sex differences in blood flow restricted isotonic knee extensions to fatigue.

AIM: It has been shown that females have greater muscular endurance than males and that this advantage is eliminated when blood flow is restricted. It is unknown if sex differences in dynamic endurance exist during low-load blood flow restricted (BFR) resistance exercise. The purpose of this study was to investigate sex differences in quadriceps femoris fatigability during isotonic knee extension exercise coupled with a blood flow restriction. METHODS: Ten males and ten females completed three sets of low-load isotonic knee extension exercises (20% of peak torque) to volitional failure under two conditions: blood flow restricted (BFR) and non-restricted free flow (FF). The number of repetitions, exercise volume, post-exercise strength loss and surface electromyography (EMG) were measured. RESULTS: Females performed more repetitions than males in the FF (252±37 vs. 112±17 repetitions; P<0.01) and BFR conditions (165±29 vs. 79±8 repetitions; P<0.01). Both sexes performed ~30% fewer repetitions during the BFR condition. MVC torque decreased approximately 37% following both conditions (P<0.01) and EMG activity increased (P<0.05) during the exercise bouts. CONCLUSION: Similar fatigue characteristics were evident in FF and BFR conditions for both sexes, and females demonstrated greater endurance, as determined by the number of repetitions completed, in both conditions. It may be beneficial to increase the relative exercise load for females in order to decrease the time under BFR.

Changes in Body Composition in Older Adults after a Technology-Based Weight Loss Intervention.

We conducted a post-hoc analysis of a pre/post, single-arm, non-randomized, multicomponent weight loss intervention in older adults. Fifty-three older adults aged ≥65 with a body mass index ≥ 30 kg/m2 were recruited to participate in a six-month, remote monitoring and video-conferencing delivered, prescriptive intervention consisting of individual and group-led registered dietitian nutrition and physical therapy sessions. We assessed weight, height, and body composition using a SECA 514 bioelectrical impedance analyzer. Mean age was 72.9±3.9 years (70% female) and all had ≥2 chronic conditions. Of those with complete data (n=30), we observed a 4.6±3.5kg loss in weight, 6.1±14.3kg (1.9%) loss in fat mass, and 0.78±1.69L loss in visceral fat (all p<0.05). Fat-free mass (-3.4kg±6.8, p=0.19), appendicular lean mass (-0.25±1.83, p=0.22), and grip strength (+3.46±7.89, p=0.56) did not significantly change. These variables were preserved after stratifying by 5% weight loss. Our intervention led to significant body and visceral fat loss while maintaining fat-free and appendicular lean muscle mass.

Reported Weight Change in Older Adults and Presence of Frailty.

OBJECTIVE: A 5% change in weight is a significant predictor for frailty and obesity. We ascertained how self-reported weight change over the lifespan impacts rates of frailty in older adults. METHODS: We identified 4,984 subjects ≥60 years with body composition measures from the National Health and Nutrition Examination Survey. An adapted version of Fried's frailty criteria was used as the primary outcome. Self-reported weight was assessed at time current,1 and 10 years earlier and at age 25. Weight changes between each time point were categorized as ≥ 5%, ≤5% or neutral. Logistic regression assessed the impact of weight change on the outcome of frailty. RESULTS: Among 4,984 participants, 56.5% were female, mean age was 71.1 years, and mean BMI was 28.2kg/m2. A weight loss of ≥ 5% had a higher association with frailty compared to current weight, age 25 (OR 2.94 [1.72,5.02]), 10 years ago (OR 1.68 [1.05,2.69]), and 1 year ago (OR 1.55 [1.02,2.36]). Weight gain in the last year was associated with increased rate of frailty (1.59 [1.09,2.32]). CONCLUSION: There is an association between frailty and reported weight loss over time while only weight gain in the last year has an association with frailty.

Association of Obesity and Frailty in Older Adults: NHANES 1999-2004.

OBJECTIVES: Body composition changes with aging can increase rates of obesity, frailty and impact function. Measuring adiposity using body fat (%BF) or central adiposity using waist circumference (WC) have greater diagnostic accuracy than traditional measures such as body mass index (BMI). DESIGN: This is an observational study. SETTING: This study focused on older community-dwelling participants. PARTICIPANTS: We identified individuals age ≥ 60 years old using the 1999-2004 cross-sectional National Health and Nutrition Survey (NHANES). INTERVENTION: The primary analysis evaluated the association between frailty and %BF or WC. Frailty was the primary predictor (robust=referent) and %BF and WC were considered continuous outcomes. Multiple imputation analyses accounted for missing characteristics. MEASUREMENT: Dual energy x-ray absorptiometry was used to assess %BF and WC was objectively measured. Frailty was defined using an adapted version of Fried's criteria that was self-reported: (low BMI<18.5kg/m2; slow walking speed [<0.8m/s]; weakness [unable to lift 10lbs]; exhaustion [difficulty walking between rooms on same floor] and low physical activity [compared to others]). Robust, pre-frail and frail persons met zero, 1 or 2, and ≥3 criteria, respectively. RESULTS: Of the 4,984 participants, the mean age was 71.1±0.2 (SE) years and 56.5% were females. We classified 2,246 (50.4%), 2,195 (40.3%), and 541 (9.2%) individuals as robust, pre-frail and frail, respectively. Percent BF was 35.9±0.13, 38.3±0.20 and 40.0±0.46 in the robust, pre-frail and frail individuals, respectively. WC was 99.5±0.32 in the robust, 100.1±0.43 in pre-frail, 104.7±1.17 in frail individuals. Compared to robust individuals, only frail individuals had greater %BF on average (ß=0.97±0.43,p=0.03); however, pre-frail and frail individuals had 2.18 and 4.80 greater WC, respectively (ß=2.18±0.64,p=0.002, and ß=4.80±1.1,p<0.001). CONCLUSION: Our results demonstrate that in older adults, frailty and pre-frailty are associated with a greater likelihood of high WC (as dichotomized) and a greater average WC (continuous).

Development and Usability Assessment of a Connected Resistance Exercise Band Application for Strength-Monitoring.

Resistance exercise bands are a core component of any physical activity strengthening program. Strength training can mitigate the development of sarcopenia, the loss of muscle mass or strength and function with aging. Yet, the adherence of such behavioral exercise strategies in a home-based setting are fraught with issues of monitoring and compliance. Our group developed a Bluetooth-enabled resistance exercise band capable of transmitting data to an open-source platform. In this work, we developed an application to capture this information in real-time, and conducted three usability studies in two mixed-aged groups of participants (n=6 each) and a group of older adults with obesity participating in a weight-loss intervention (n=20). The system was favorable, acceptable and provided iterative information that could assist in future deployment on ubiquitous platforms. Our formative work provides the foundation to deliver home-based monitoring interventions in a high-risk, older adult population.

In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. IV. Cytotoxic effect of an anti-T11-gelonin immunotoxin.

The cytotoxic effect of a lymphocyte-specific immunotoxin formed by disulfide conjugation of an anti-T11 monoclonal antibody with the ribosome-inactivating protein gelonin was assessed in vitro on peripheral blood T cells and in vivo on splenic and lymph node T cells of macaque monkeys. This immunotoxin was cytotoxic to proliferating peripheral blood T cells in vitro as measured by both direct and indirect assays. Two sequential intravenous infusions into macaque monkeys achieved plasma concentrations of immunotoxin far in excess of those shown to be cytotoxic for cultured T cells and coated all T cells in lymph nodes and spleen with intact immunotoxin for four days. However, the cytotoxic effect of the immunotoxin on T cells in vivo was considerably less than that predicted by the in vitro studies. Further experiments suggested that the state of activation of the targeted T cell population in vivo, or the appearance of anti-immunotoxin antibodies, which occurred in all infused monkeys, might attenuate immunotoxin-mediated cell killing in vivo. These studies illustrate the significant differences between the action of immunotoxin conjugates in vitro, and those seen when these conjugates are utilized as therapeutic agents in vivo.

Immunoconjugates containing novel maytansinoids: promising anticancer drugs.

The potential of immunoconjugates of cytotoxic drugs for the treatment of cancer has not yet been realized owing to the difficulty of delivering therapeutic concentrations of these drugs to the target cells. In an effort to overcome this problem we have synthesized maytansinoids that have 100- to 1000-fold higher cytotoxic potency than clinically used anticancer drugs. These maytansinoids are linked to antibodies via disulfide bonds, which ensures the release of fully active drug inside the cells. The conjugates show high antigen-specific cytotoxicity for cultured human cancer cells (50% inhibiting concentration, 10 to 40 pM), low systemic toxicity in mice, and good pharmacokinetic behavior.

Negative dose-response relationship for radiation-induced micronuclei in polychromatic erythrocytes of mice.

Micronuclei were assessed among the bone marrow PCEs of mice 28 hr after exposures to 1 to 8 Gy of X-rays and at 6-hr intervals from 12-60 hr after exposures to 2 or 6 Gy. At 28 hr, the frequency of micronuclei declined as the exposure level increased from 1 to 8 Gy. The peak proportion of micronucleated PCEs appeared much later following 6 Gy than after 2 Gy exposures, implicating cell cycle delay as the cause of the negative dose-response relationship.