Dose Response of Acute ATP Supplementation on Strength Training Performance

Background: Chronic oral ATP supplementation benefits cardiovascular health, muscular performance, body composition, and recovery while attenuating muscle breakdown and fatigue. A single 400 mg dose of oral ATP supplementation improved lower body resistance training performance and energy expenditure in recreational resistance trained males, however, the minimal effective dose is currently unknown.Materials and Methods: Twenty recreationally trained men (age 28.6 ± 1.0 years, body mass 81.2 ± 2.0 kg, height 175.2 ± 1.4 cm, 1RM 141.5 ± 5.0 kg) consumed a single dose of either 400 mg, 200 mg, or 100 mg ATP (PEAK ATP®, TSI USA LLC, Missoula, MT, USA) or a placebo in a randomized, placebo-controlled crossover design, separated by a one week wash out between treatments. After warm-up, participants performed 4 sets of half-squats using free-weights until movement failure separated by 2 mins of rest between sets.Results: In comparison to placebo, 400 mg ATP significantly increased the number of set 1 repetitions (+13%, p = 0.04), and numerically increased total repetitions (+7%, p = 0.19) and total weight lifted (+6%, p = 0.22). 200 mg ATP numerically increased set 1 repetitions (+4% p = 0.47), while 100 mg ATP showed no improvements over placebo. 100 mg ATP (−4%, p < 0.05) and 400 mg ATP (−4%, p = 0.11) decreased the perceived rate of exertion compared to placebo.Conclusions: In this study, the effective minimal dose of acute oral ATP supplementation during resistance exercise to increase performance was determined to be 400 mg, while as little as 100 mg showed improvements in perceived exertion.

Potential Benefits of a Minimal Dose Eccentric Resistance Training Paradigm to Combat Sarcopenia and Age-Related Muscle and Physical Function Deficits in Older Adults

The ability of older adults to perform activities of daily living is often limited by the ability to generate high mechanical outputs. Therefore, assessing and developing maximal neuromuscular capacity is essential for determining age-related risk for functional decline as well as the effectiveness of therapeutic interventions. Interventions designed to enhance neuromuscular capacities underpinning maximal mechanical outputs could positively impact functional performance in daily life. Unfortunately, < 10% of older adults meet the current resistance training guidelines. It has recently been proposed that a more “minimal dose” RT model may help engage a greater proportion of older adults, so that they may realize the benefits of RT. Eccentric exercise offers some promising qualities for such an approach due to its efficiency in overloading contractions that can induce substantial neuromuscular adaptations. When used in a minimal dose RT paradigm, eccentric-based RT may be a particularly promising approach for older adults that can efficiently improve muscle mass, strength, and functional performance. One approach that may lead to improved neuromuscular function capacities and overall health is through heightened exercise tolerance which would favor greater exercise participation in older adult populations. Therefore, our perspective article will discuss the implications of using a minimal dose, submaximal (i.e., low intensity) multi-joint eccentric resistance training paradigm as a potentially effective, and yet currently underutilized, means to efficiently improve neuromuscular capacities and function for older adults.

Are Efficient-Dose Mixtures a Solution to Reduce Fungicide Load and Delay Evolution of Resistance? An Experimental Evolutionary Approach

Pesticide resistance poses a critical threat to agriculture, human health and biodiversity. Mixtures of fungicides are recommended and widely used in resistance management strategies. However, the components of the efficiency of such mixtures remain unclear. We performed an experimental evolutionary study on the fungal pathogen Z. tritici to determine how mixtures managed resistance. We compared the effect of the continuous use of single active ingredients to that of mixtures, at the minimal dose providing full control of the disease, which we refer to as the “efficient” dose. We found that the performance of efficient-dose mixtures against an initially susceptible population depended strongly on the components of the mixture. Such mixtures were either as durable as the best mixture component used alone, or worse than all components used alone. Moreover, efficient dose mixture regimes probably select for generalist resistance profiles as a result of the combination of selection pressures exerted by the various components and their lower doses. Our results indicate that mixtures should not be considered a universal strategy. Experimental evaluations of specificities for the pathogens targeted, their interactions with fungicides and the interactions between fungicides are crucial for the design of sustainable resistance management strategies.

Efficacy and Safety of Dupilumab in Moderate-to-Severe Bullous Pemphigoid

BackgroundBullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. As the main treatment for BP, systemic corticosteroids are often limited by their side effects. Safer treatment modalities are therefore needed. Dupilumab is a biologic agent used to treat BP in recent years.MethodsMedical records of patients with moderate-to-severe BP were retrospectively reviewed. Twenty-four patients were included (follow-up period: 32 weeks), eight of whom received dupilumab in combination with methylprednisolone and azathioprine (dupilumab group) while the other 16 patients received methylprednisolone and azathioprine (conventional group). Response to dupilumab was evaluated by comparison of several parameters (time to stop new blister formation, time to reduce the systemic glucocorticoids to minimal dose, and total amount of methylprednisolone).ResultsThe median age of patients in the dupilumab and conventional groups were 64.50 years (range: 22–90 years) and 64.50 years (range: 17–86 years), respectively. The median duration of disease before admission in the dupilumab group was 2 months (range: 1–240 months) and 2.5 months (range: 1–60 months) in the conventional group. The median time to stop new blister formation was 8 days (range: 1–13 days) and 12 days (range: 5–21 days) in patients of the dupilumab and conventional groups, respectively (p = 0.028 by Kaplan-Meier analysis). In addition, the median time to reduce the systemic glucocorticoids to minimal dose (methylprednisolone 0.08 mg/kg/day) was 121.5 and 148.5 days for the dupilumab and conventional therapy groups, respectively (p = 0.0053 by Kaplan-Meier analysis). The median total amount of methylprednisolone (at the time of reaching the minimal dose) used in the dupilumab group was 1,898 mg (range: 1,624–2,932 mg) while the cumulative dose of conventional group was 2,344 mg (range: 1,708–4,744 mg) (p = 0.036 by Mann-Whitney U test). The median total amount of azathioprine (at the time of reaching the minimal dose) used in dupilumab group was 8,300 mg (range: 7,100–10,400 mg) while the total dose of conventional group was 10,300 mg (range: 8,900–14,400 mg) (p = 0.0048 by Mann-Whitney U test). No adverse event related to dupilumab was recorded.ConclusionsDupilumab in addition to methylprednisolone and azathioprine seems superior to methylprednisolone/azathioprine alone in controlling disease progression and accelerating the tapering of glucocorticoids.

Why do fungicide mixtures delay the evolution of resistance? An experimental evolutionary approach

Pesticide resistance poses a critical threat to agriculture, human health and biodiversity. Mixtures of fungicides are recommended and widely used in resistance management strategies. However, the components of the efficiency of such mixtures remain unclear. We performed an experimental evolution study on the fungal pathogen Z. tritici, to determine how mixtures managed resistance. We compared the effect of the continuous use of single active ingredients to that of mixtures, at the minimal dose providing full control of the disease, which we refer to as the "efficient" dose. We found that the performance of efficient-dose mixtures against an initially susceptible population depended strongly on the components of the mixture. Such mixtures were either as durable as the best mixture component used alone, or worse than all components used alone. Moreover, efficient-dose mixture regimes probably select for generalist resistance profiles as a result of the combination of selection pressures exerted by the various components and their lower doses. Our results indicate that mixtures should not be considered a universal strategy. Experimental evaluations of specificities for the pathogens targeted, their interactions with fungicides and the interactions between fungicides are crucial for the design of sustainable resistance management strategies.

Efficacy of oral nifedipine as a tocolytic agent

Background: Preterm birth is defined as birth at less than 37 weeks period of gestation, is the most important single determinant of adverse infant outcome in terms of both survival and quality of life. The need for tocolysis in terms of safety and efficacy is necessary to decrease perinatal mortality and morbidity in preterm labour. This study was aimed to evaluate the effectiveness of nifedipine as a tocolytic for inhibiting uterine contraction in threatened preterm labour.Methods: It was a prospective, nonblinded, single centred, randomized control trial. This study included 100 cases of preterm labour admitted in department of obstetrics and gynaecology, KIMSH, Bangalore, who satisfied the inclusion and exclusion criteria and were administered with nifedipine tocolysis.Results: 100 cases of preterm were evaluated for the prolongation of pregnancy for more than 48 hours. Prolongation of pregnancy till term was observed in 88% of the cases administered with nifedipine tocolysis. The mean gestational age in each group was 32.58±1.95 weeks. Nifedipine had very few side effects, namely tachycardia and headache and no changes in fetal heart rate.Conclusions: In this study oral nifedipine was found to be efficacious in prolongation of pregnancy for more than 48 hours with the ease of oral administration and with minimal dose tocolytic effect was achieved. It had minimal maternal and neonatal side effects and eliminate the need for intensive maternal monitoring.

A minimal dose of unmanipulated bone marrow infusion without conditioning for T-B+NK- severe combined immunodeficiency

Hematopoietic stem cell transplantation (HSCT) is the standard method of reconstituting immune function in severe combined immunodeficiency (SCID); however, there is no consensus about optimal cell doses. In this study, we investigated HSCT outcomes and immune reconstitution, following minimal dose (MD) HSCT in T cell-negative (T-), B cell-positive (B+), natural killer cell-negative (NK-) SCID patients. We retrospectively reviewed patients with SCID who received HSCT between 2002–2018. Standard dose (SD) and MD were classified based on a total nucleated cell count (TNC) of 1.0 × 108/kg or more and less. Total seven patients with SCID received HSCT. MD group (n = 4) were administered 5 mL or less of bone marrow without conditioning, with median TNC and CD34+ cell counts of 0.49 × 108/kg and 0.62 × 106/kg, respectively. T cells recovered within a year, and immunoglobulin supplementation was discontinued at median 3.5 months after HSCT in all MD recipients. All MD recipients were alive without disease recurrence at a median of 126.9 months after HSCT, exhibiting donor chimerism in the range of 10.1–100%. In patients with T-B + NK- SCID, sufficient therapeutic effects were safely obtained with minimal dose of bone marrow infusion without conditioning.