Effects of Preferred vs. Nonpreferred Music on Resistance Exercise Performance.

ABSTRACT: Ballmann, CG, McCullum, MJ, Rogers, RR, Marshall, MR , and Williams, TD. Effects of preferred vs. nonpreferred music on resistance exercise performance. J Strength Cond Res 35(6): 1650-1655, 2021-The purpose of this study was to examine the effects of listening to preferred vs. nonpreferred music on resistance exercise performance. Twelve resistance-trained college-aged males (age = 20.5 ± 1.24 years, height = 183.9 ± 6.8 cm, and body mass = 97.0 ± 18.2 kg) were recruited for this study. In a within-groups counterbalanced study design, subjects either listened to preferred or nonpreferred music during a bench press exercise test. Subjects completed as many repetitions as possible at 75% of their 1 repetition maximum with maximum explosive intent. Power and velocity of the barbell movement was measured for the first 3 repetitions using a linear position transducer. Motivation was measured using a visual analog scale immediately after exercise. Each exercise trial was separated by a 48-hour washout period. Results indicate that listening to preferred music increased overall bench press repetitions completed (p = 0.005; effect size [ES] = 0.84). During the first 3 repetitions, mean velocity (p = 0.001; ES = 1.6), relative mean power (p = 0.012; ES = 0.55), peak velocity (p = 0.011; ES = 0.99), and peak power (p = 0.009; ES = 0.35) were higher while listening to preferred music vs. nonpreferred music. Finally, motivation during the lift (p < 0.001; ES = 5.9) was significantly higher while listening to preferred vs. nonpreferred music. Current findings suggest that listening to preferred music by the individual results in greater performance than nonpreferred during resistance exercise. Athletes may benefit from the option to listen to their preferred music to increase motivation and resistance exercise performance.

Development of a Long-Wave Infrared Band-Edge (LWIR BE) thermometry instrument.

Accurate measurement of substrate temperature is one of the most critical process control parameters for molecular beam epitaxy (MBE) growth. Band-edge thermometry instruments have proven to be a valuable tool for process control during MBE growth of semiconductor films, providing as high as ±1 °C temperature resolution. The increasing use of InAs, GaSb, and AlSb iii-v materials necessitates a method for accurately measuring the temperature of their closely lattice-matched GaSb substrates. Current-technology instruments typically rely on InGaAs detector materials which have a maximum wavelength λ detection of ∼1.7 µm, but GaSb substrates have a band gap energy corresponding to λ > 2 µm. A band-edge thermometry instrument capable of λ > 2 µm has been developed using an InAs/InGaSb strained-layer superlattice detector sensitive to 2-9.5 µm long-wave IR wavelengths.

A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study.

Treatment of carriers of the CYP2C19*2 allele and ABCB1 TT genotype with clopidogrel is associated with increased ischemic complications after percutaneous coronary intervention (PCI). We sought to evaluate a pharmacogenomic strategy among patients undergoing PCI for ST-elevation myocardial infarction (STEMI), by performing a randomized trial, enrolling 102 patients. Point-of-care genetic testing for CYP2C19*2, ABCB1 TT and CYP2C19*17 was performed with carriers of either the CYP2C19*2 allele or ABCB1 TT genotype randomly assigned to a strategy of prasugrel 10 mg daily or an augmented dosing strategy of clopidogrel (150 mg daily for 6 days then 75 mg daily). The primary end point was the proportion of at-risk carriers exhibiting high on-treatment platelet reactivity (HPR), a marker associated with increased adverse cardiovascular events, after 1 month. Fifty-nine subjects (57.8%) were identified as carriers of at least one at-risk variant. Treatment with prasugrel significantly reduced HPR compared with clopidogrel by P2Y12 reaction unit (PRU) thresholds of >234 (0 vs 24.1%, P=0.0046) and PRU>208 (3.3 vs 34.5%, P=0.0025). The sensitivity of point-of-care testing was 100% (95% CI 88.0-100), 100% (86.3-100) and 96.9% (82.0-99.8) and specificity was 97.0% (88.5-99.5), 97.1% (89.0-99.5) and 98.5% (90.9-99.9) for identifying CYP2C19*2, ABCB1 TT and CYP2C19*17, respectively. Logistic regression confirmed carriers as a strong predictor of HPR (OR=6.58, 95% CI 1.24-34.92; P=0.03). We confirmed that concurrent identification of three separate genetic variants in patients with STEMI receiving PCI is feasible at the bedside. Among carriers of at-risk genotypes, treatment with prasugrel was superior to an augmented dosing strategy of clopidogrel in reducing HPR.

Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression.

Although adverse early life experiences have been found to increase lifetime risk to develop violent behaviors, the neurobiological mechanisms underlying these long-term effects remain unclear. We present a novel animal model for pathological aggression induced by peripubertal exposure to stress with face, construct and predictive validity. We show that male rats submitted to fear-induction experiences during the peripubertal period exhibit high and sustained rates of increased aggression at adulthood, even against unthreatening individuals, and increased testosterone/corticosterone ratio. They also exhibit hyperactivity in the amygdala under both basal conditions (evaluated by 2-deoxy-glucose autoradiography) and after a resident-intruder (RI) test (evaluated by c-Fos immunohistochemistry), and hypoactivation of the medial orbitofrontal (MO) cortex after the social challenge. Alterations in the connectivity between the orbitofrontal cortex and the amygdala were linked to the aggressive phenotype. Increased and sustained expression levels of the monoamine oxidase A (MAOA) gene were found in the prefrontal cortex but not in the amygdala of peripubertally stressed animals. They were accompanied by increased activatory acetylation of histone H3, but not H4, at the promoter of the MAOA gene. Treatment with an MAOA inhibitor during adulthood reversed the peripuberty stress-induced antisocial behaviors. Beyond the characterization and validation of the model, we present novel data highlighting changes in the serotonergic system in the prefrontal cortex-and pointing at epigenetic control of the MAOA gene-in the establishment of the link between peripubertal stress and later pathological aggression. Our data emphasize the impact of biological factors triggered by peripubertal adverse experiences on the emergence of violent behaviors.

Characterization of a major colon cancer susceptibility locus (Ccs3) on mouse chromosome 3.

Treatment of mice with the carcinogen azoxymethane (AOM) induces a number of lesions in the colon, including hyperplastic lesions, as well adenomas and carcinomas in situ. Inbred strains of mice show different responses to AOM-induced carcinogenesis. A/J mice are highly susceptible and develop a greater number of hyperplastic lesions and tumors (15-70 tumors per mouse) than resistant C57BL/6J mice (0-6 tumors per mouse). Susceptibility to AOM-induced tumors segregates as a co-dominant trait in (A x B6)F1 hybrids. Using a set of 23 AcB and BcA recombinant congenic mouse strains derived from A/J (susceptible) and B6 (resistant) parents, we observed that the number of hyperplastic lesions and tumors induced by AOM was under different genetic controls in AcB/BcA strains. The multiplicity of AOM-induced tumors is controlled by a major locus that we have mapped on the distal portion of chromosome 3, to which we have given the temporary designation colon cancer susceptibility locus 3 (Ccs3). B6 and A/J alleles at Ccs3 are associated with resistance and susceptibility, respectively. Haplotype analysis in key informative AcB/BcA strains restricts the size of the Ccs3 locus to a 14 Mb segment that contains 94 annotated genes. The expression level of all these genes in normal colon has been established by transcript profiling with microarrays, and has led to the identification of a subset of positional candidates that are expressed at high levels in this tissue. The 4q and 1p human chromosomal segments sharing syntenic homology with the mouse Ccs3 segment are known to be associated with inflammatory bowel diseases and colorectal tumors in humans, suggesting that the study of the mouse Ccs3 locus may help further the pathogenesis of these human conditions.

Doxycycline-controlled splicing modulation by regulated antisense U7 snRNA expression cassettes.

Many diseases affect pre-mRNA splicing, and alternative splicing is a major source of proteome diversity and an important mechanism for modulating gene expression. The ability to regulate a specific splicing event is therefore desirable; for example, to understand splicing-associated pathologies. We have developed methods based on modified U7 snRNAs, which allow us to induce efficient skipping or inclusion of selected exons. Here, we have adapted these U7 tools to a regulatable system that relies on a doxycycline-sensitive version of the Krüppel-associated box (KRAB)/KAP1 transcriptional silencing. Co-transduction of target cells with two lentiviral vectors, one carrying the KRAB protein and the other the regulatable U7 cassette, allows a tight regulation of the modified U7 snRNA. No leakage is observed in the repressed state, whereas full induction can be obtained with doxycycline in ng ml(-1) concentrations. Only a few days are necessary for a full switch, and the induction/repression can be repeated over several cycles without noticeable loss of control. Importantly, the U7 expression correlates with splicing correction, as shown for the skipping of an aberrant beta-globin exon created by a thalassaemic mutation and the promotion of exon 7 inclusion in the human SMN2 gene, an important therapeutic target for spinal muscular atrophy.

Genetic analysis of resistance to infections in mice: A/J meets C57BL/6J.

Susceptibility to infectious diseases has long been known to have a genetic component in human populations. This genetic effect is often complex and difficult to study as it is further modified by environmental factors including the disease-causing pathogen itself. The laboratory mouse has proved a useful alternative to implement a genetic approach to study host defenses against infections. Our laboratory has used genetic analysis and positional cloning to characterize single and multi-gene effects regulating inter-strain differences in the susceptibility of A/J and C57BL/6J mice to infection with several bacterial and parasitic pathogens. This has led to the identification of several proteins including Nrampl (Slc11a1), Birc1e, Icsbp, C5a, and others that play critical roles in the antimicrobial defenses of macrophages against intracellular pathogens. The use of AcB/BcA recombinant congenic strains has further facilitated the characterization of single gene effects in complex traits such as susceptibility to malaria. The genetic identification of erythrocyte pyruvate kinase (Pklr) and myeloid pantetheinase enzymes (Vnn1/3) as key regulators of blood-stage parasitemia has suggested that cellular redox potential may be a key biochemical determinant of Plasmodium parasite replication. Expanding these types of studies to additional inbred strains and to emerging stocks of mutagenized mice will undoubtedly continue to unravel the molecular basis of host defense against infections.

Forward genetic dissection of immunity to infection in the mouse.

Forward genetics is an experimental approach in which gene mapping and positional cloning are used to elucidate the molecular mechanisms underlying phenotypic differences between two individuals for a given trait. This strategy has been highly successful for the study of inbred mouse strains that show differences in innate susceptibility to bacterial, parasitic, fungal, and viral infections. Over the past 20 years, these studies have led to the identification of a number of cell populations and critical biochemical pathways and proteins that are essential for the early detection of and response to invading pathogens. Strikingly, the macrophage is the point of convergence for many of these genetic studies. This has led to the identification of diverse pathways involved in extracellular and intracellular pathogen recognition, modification of the properties and content of phagosomes, transcriptional response, and signal transduction for activation of adaptive immune mechanisms. In models of viral infections, elegant genetic studies highlighted the pivotal role of natural killer cells in the detection and destruction of infected cells.

Neonatal lesions of the ventral hippocampus in rats lead to prefrontal cognitive deficits at two maturational stages.

This experiment assessed the effect of neonatal ventral hippocampus lesions in rats, a heuristic approach to model schizophrenia, on continuous delayed alternation and conditional discrimination learning performance before and after complete cerebral maturation. Delays (0, 5, 15, and 30 s) were introduced in the tasks to help dissociate between a hippocampal and a prefrontal cortex dysfunction. At postnatal day (PND) 6 or 7, rats received bilateral microinjections of ibotenic acid or phosphate-buffered saline in the ventral hippocampus. From PND 26 to PND 35, rats were tested on the alternation task in a T-maze; from PND 47 to PND 85, the same rats were tested in the discrimination task where a stimulus and a response location had to be paired. Deficits in ventral hippocampus-lesioned rats were observed in both tasks whether a delay was introduced before a response or not. Impaired performance regardless of delay length, combined with high rates of perseverative errors, suggested a post-lesional prefrontal cortex dysfunction which persisted from the juvenile stage into adulthood. Premature cognitive impairments could not be predicted on the basis of the neurodevelopmental animal model of schizophrenia. Nevertheless, they appear consistent with accounts of premorbidly compromised memory, both immediate and delayed, in subgroups of schizophrenia patients.

Review article: tolevamer, a novel toxin-binding polymer: overview of preclinical pharmacology and physicochemical properties.

BACKGROUND: Tolevamer is a novel toxin-binding polymer that is currently being investigated in clinical trials for the treatment of patients who have Clostridium difficile-associated diarrhoea. AIMS: To summarize the results of in vitro and in vivo preclinical studies of tolevamer. In contrast to antibiotics, tolevamer binds C. difficile toxins to interrupt toxin-mediated intestinal inflammation and tissue damage, and does not demonstrate direct antimicrobial activity. METHODS: Pharmacokinetics/pharmacodynamics were studied in rats and dogs; efficacy was studied in a hamster model. RESULTS: Studies in rats and dogs indicate that tolevamer is essentially non-absorbed from the gastrointestinal tract and show that drug interactions with commonly used therapies are unlikely. Pharmacologic studies indicate that tolevamer reduces disease severity and recurrence rates in the hamster model of C. difficile-associated diarrhoea and blocks the enterotoxic effects of toxin A in rat ileum. The binding parameters calculated for the interaction of tolevamer with toxins A and B provide a reasonable physicochemical model that supports the potential clinical utility of tolevamer. CONCLUSIONS: These preclinical results are consistent with the effectiveness and safety profile of tolevamer observed in clinical studies in patients with C. difficile-associated diarrhoea.

Resistance mechanism development to the topoisomerase-I inhibitor Hoechst 33342 by Leishmania donovani.

The bisbenzimidazole compound Hoechst 33342 (Ho342) has been identified as a specific Topoisomerase-I (Topo-I) inhibitor in mammalian cells. More recently, we have reported the ability of Ho342 to target L. donovani Topo-I, leading to parasite growth inhibition in vitro by mechanisms involving DNA breakage and apoptosis-like phenomenon. As the Ho342 lead molecule (2,5'-Bi-1H-benzimidazole) can be used as a starting structure for derivative compounds more effective against Leishmania, defining the Ho342 resistance mechanism(s) in Leishmania represents an important strategic tool. In the present study, we selected resistant parasites to Ho342 (LdRHo.300). While we observed an increase of the Topo-I gene expression correlated by a higher Topo-I DNA relaxation activity, the Topo-I genes (LdTOP1A and LdTOP1B) sequencing did not reveal any mutation for the resistant parasites. Moreover, our results on Ho342 cellular accumulation suggested the presence of a potential energy-dependent Ho342 transporter in the wild-type parasite, and that an alteration of this transporter has occurred in LdRHo.300, leading to an altered drug accumulation. Collectively, Ho342 resistance characterization provided results supporting that the resistance developed by LdRHo.300 involves complex mechanisms, most likely dominated by an altered drug accumulation, providing new insight in the Ho342 resistance mechanisms.

Conceptualizing and measuring family quality of life.

BACKGROUND: Increasing emphasis on family-centred approaches to services and supports for families of children with disabilities has surfaced the issue of accountability for family outcomes. We present a review of literature about the impacts of children with disabilities on families as a backdrop to proposing family quality of life as a concept that encompasses impacts of disability and one that can be used to assess the impact of supports and services on families. METHOD: We briefly introduce the Beach Center Family Quality of Life Scale, providing information about its factor structure, reliability and convergent validity. RESULTS: The Beach Center Family Quality of Life Scale contains 25 items assessing family ratings of importance and satisfaction with five domains: Family interaction, Parenting, Emotional well-being, Physical/material well-being and Disability-related supports. CONCLUSION: We present a framework for utilizing a measure of family quality of life as a long-term outcome in concert with other short-term measures of service outcomes for families.

Device closure of a patent foramen ovale in a patient with lipomatous hypertrophy of the atrial septum.

The presence of a patent foramen ovale has been recognized as a risk factor for embolic stroke, and transcatheter device closure of patent foramen ovales is increasingly performed to reduce future neurological events. The present report discusses a patient who continued to have residual shunting following percutanous closure because of improper seating of the device in the presence of a lipomatous atrial septum.

Design, synthesis, and evaluation of estradiol-linked genotoxicants as anti-cancer agents.

A series of bifunctional compounds was prepared consisting of 17beta estradiol linked to a DNA damaging N,N-bis-(2-chloroethyl)aniline. The objective of our studies was to determine the characteristics of the linker that permitted both reaction with DNA and binding of the resultant covalent adducts to the estrogen receptor. Linker characteristics were pivotal determinants underlying the ability of the compounds to kill selectively breast cancer cells that express the estrogen receptor.

Toward assessing family outcomes of service delivery: validation of a family quality of life survey.

BACKGROUND: The concept of family quality of life (QoL) has emerged as an important outcome of service delivery for individuals with disabilities and their families. The present study describes the process of developing a tool to measure family QoL. METHODS AND RESULTS: A total of 1197 respondents participated in a national field test. Through factor analysis, the survey was refined in several ways: (1) the preliminary 10-domain structure was reduced to a five-domain structure; (2) a total of 41 items were selected for the revised survey; and (3) wordings were clarified. CONCLUSIONS: The implications for future research and practice are discussed.

Consequence of Hoechst 33342-mediated Leishmania DNA topoisomerase-I inhibition on parasite replication.

This study reports that inhibition of Leishmania Topo-I with the minor groove-binding ligands (MGBLs) Hoechst 33342 (Ho342) blocks parasite growth in culture by mechanisms involving DNA breakage. While Ho342 inhibited the replication of several species of Leishmania in a dose- and time-dependent manner, Ho258 was not effective. Cytofluorometric analysis suggested that superior effectiveness of Ho342 over Ho258 was attributed to Leishmania parasites being more permeable toward Ho342. This observation was supported by the ability of both Ho342 and Ho258 to block the relaxation of supercoiled pBR322 DNA by Leishmania Topo-I. The Ho342 specificity toward L. donovani Topo-I was reinforced by the observation that increased Topo-I gene expression and Topo-I activity in Leishmania was paralleled by augmented resistance for this compound. Furthermore, the capacity of NaCl treatment to reverse MGBL-mediated DNA break suggests that Ho342 targetted Topo-I. Moreover, we observed that Ho342-inducible arrest of Leishmania growth was accompanied by G1 arrest and induction of cell death that closely resembles apoptosis. Taken together, our results suggest that MGBL compounds show promise as Topo-I inhibitors against Leishmania infection.

Effects of risperidone on aberrant behavior of persons with developmental disabilities: I. A double-blind crossover study using multiple measures.

The efficacy of the atypical antipsychotic risperidone was evaluated in the treatment of aberrant behavior (e.g., aggression, self-injury) in 20 individuals with developmental disabilities. A double-blind, crossover design was used to compare risperidone with placebo in a 22-week trial with a 6-month follow-up phase. Based on a 50% reduction in mean Aberrant Behavior Checklist--Community total scores, 50% of the participants were identified as responders. Naturalistic observations of a subset of five individuals showed that for 4 out of 5 participants, risperidone was effective in reducing aberrant behavior. Side effects included weight gain (84% of participants) and sedation (40% of participants). The advantages of conducting a comprehensive analysis of the effects of medication on aberrant behavior are discussed.

Treatment of visceral leishmaniasis with sterically stabilized liposomes containing camptothecin.

The efficacy of 20(S)-camptothecin (CPT), free and incorporated into sterically stabilized liposomes, has been investigated in vitro against Leishmania donovani promastigotes and in vivo in a murine model of visceral leishmaniasis. Incubation of L. donovani promastigotes with free or liposomal CPT inhibited the growth of parasites in a dose-dependent manner. Tissue distribution studies revealed that the intraperitoneal administration of liposomal CPT was efficient for the delivery of high drug levels to the liver and spleen. Treatment of infected mice with intraperitoneal injections of free and liposomal CPT significantly reduced the parasite loads in the livers by 43 and 55%, respectively, compared with the loads for untreated controls. However, both treatments caused normochromic anemia and neutropenia.

Language decline across the life span: findings from the Nun Study.

The present study examines language samples from the Nun Study. Measures of grammatical complexity and idea density were obtained from autobiographies written over a 60-year span. Participants who had met criteria for dementia were contrasted with those who did not. Grammatical complexity initially averaged 4.78 (on a 0-to-7-point scale) for participants who did not meet criteria for dementia and declined .04 units per year; grammatical complexity for participants who met criteria for dementia initially averaged 3.86 and declined .03 units per year. Idea density averaged 5.35 propositions per 10 words initially for participants who did not meet criteria for dementia and declined an average of .03 units per year, whereas idea density averaged 4.34 propositions per 10 words initially for participants who met criteria for dementia and declined .02 units per year. Adult experiences, in general, did not moderate these declines.