CaMKK2 as an emerging treatment target for bipolar disorder.

Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug targets. A compelling new treatment target is the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme. CaMKK2 is highly enriched in brain neurons and regulates energy metabolism and neuronal processes that underpin higher order functions such as long-term memory, mood, and other affective functions. Loss-of-function polymorphisms and a rare missense mutation in human CAMKK2 are associated with bipolar disorder, and genetic deletion of Camkk2 in mice causes bipolar-like behaviours similar to those in patients. Furthermore, these behaviours are ameliorated by lithium, which increases CaMKK2 activity. In this review, we discuss multiple convergent lines of evidence that support targeting of CaMKK2 as a new treatment strategy for bipolar disorder.

Validity and Test-Retest Reliability of the 1080 Quantum System for Bench Press Exercise.

Boehringer, S and Whyte, DG. Validity and test-retest reliability of the 1080 Quantum System for bench press exercise. J Strength Cond Res 33(12): 3242-3251, 2019-This study assessed the validity and reliability of the 1080 Quantum (1080Q) during the bench press exercise. Twenty-seven resistance-trained men (28 ± 4 years; body mass 88.9 ± 12.8 kg; 1 repetition maximum [1RM] bench press 94.8 ± 10.7 kg) completed 2 test-retest sessions, separated by 1 week. In each session, subjects performed single repetitions at 30, 40, 50, 60, 70, and 80% of their bench press 1RM. Mean velocity (Vmean), peak velocity (Vpeak), mean force (Fmean), peak force (Fpeak), mean power (Pmean), and peak power (Ppeak) were simultaneously assessed using the 1080Q Synchro and a linear position transducer (GymAware; Kinetic Performance Technology, Canberra, Australia). The overall performance of the 1080Q was both valid (r = 0.94-1.00) and reliable (coefficient of variation [CV] = 1.7-8.0%, intraclass correlation coefficient [ICC] = 0.90-1.00) for all measures, although both fixed and systematic biases were present. When assessed at each of the relative loads, the 1080Q remained valid for all measures apart from Fmean at 30% 1RM (r = 0.78) and Fpeak at 70 (r = 0.81) and 80% (r = 0.57) 1RM. The 1080Q also demonstrated excellent reliability at all relative loads apart from the heaviest, where Vmean (CV = 11.0%, ICC = 0.69), Pmean (CV = 11.4%, ICC = 0.65), and Ppeak (CV = 10.2%, ICC = 0.79) reliability was reduced. These data indicate that athletes and strength and conditioning coaches can confidently use the 1080Q to monitor training progression; however, caution should be taken when assessing performance measures at the either end of the load spectrum.

The Epidemiology of Low Back Pain and Injury in Dance: A Systematic Review.

BACKGROUND: Dance is a physical pursuit that involves loading the spine through repetitive dynamic movements and lifting tasks. As such, low back pain (LBP) and low back injury (LBI) have been identified as common health problems in contemporary and classical ballet dancers. However, clarity regarding the experience of LBP and LBI in dance is lacking. OBJECTIVES: To systematically review and synthesize the epidemiology of LBP and LBI in dance populations. METHODS: A comprehensive search of 6 electronic databases, back catalogs of dance science-specific journals, and reference lists of relevant articles and a forward citation search were performed. RESULTS: Fifty full-text articles were included in the final systematic review. There was considerable methodological heterogeneity among the included studies. The median (range) point, yearly, and lifetime prevalence of LBP was 27% (17%-39%), 73% (41%-82%), and 50% (17%-88%), respectively. The lower back contributed to 11% (4%-22%) of time loss and 11% (5%-23%) of medical-attention injuries. CONCLUSION: Dancers are vulnerable to LBP and LBI. The use of definitions that are sensitive to the complexity of LBP and LBI would facilitate improved understanding of the problem within dance, inform health care strategies, and allow for monitoring LBP-specific intervention outcomes. J Orthop Sports Phys Ther 2019;49(4):239-252. Epub 18 Jan 2019. doi:10.2519/jospt.2019.8609.

Multi-segment spine kinematics: Relationship with dance training and low back pain.

BACKGROUND: Spine posture, range of motion (ROM) and movement asymmetry can contribute to low back pain (LBP). These variables may have greater impact in populations required to perform repetitive spine movements, such as dancers; however, there is limited evidence to support this. RESEARCH QUESTION: What is the influence of dance and LBP on spinal kinematics? METHODS: In this cross-sectional study, multi-segment spinal kinematics were examined in 60 female participants, including dancers (n = 21) and non-dancers (n = 39) with LBP (n = 33) and without LBP (n = 27). A nine-camera motion analysis system sampling at 100 Hz was used to assess standing posture, as well as ROM and movement asymmetry for side bend and trunk rotation tasks. A two-way ANOVA was performed for each of the outcome variables to detect any differences between dancers and non-dancers, or individuals with and without LBP. RESULTS: Compared to non-dancers, dancers displayed a flatter upper lumbar angle when standing (p < 0.01, ηp2 = 0.15), and achieved greater frontal plane ROM for the upper lumbar (p = 0.04, ηp2 = 0.08) and lower thoracic (p = 0.02, ηp2 = 0.09) segments. There were no differences between dancers and non-dancers for transverse plane ROM (p > 0.05) or movement asymmetry (p > 0.05). There was no main effect for LBP symptoms on any kinematic measures, and no interaction effect for dance group and LBP on spinal kinematics (p > 0.05). SIGNIFICANCE: Female dancers displayed a flatter spine posture and increased spine ROM compared to non-dancers for a select number of spine segments and movement tasks. However, the overall number of differences was small, and no relationship was observed between LBP and spinal kinematics. This suggests that these simple, static posture, ROM, and asymmetry measures often used in clinical practice can provide only limited generalisable information about the impact of dance or LBP on spinal kinematics.

The prevalence and impact of low back pain in pre-professional and professional dancers: A prospective study.

OBJECTIVES: To determine the prevalence of low back pain (LBP) in pre-professional and professional dancers and its impact on dance participation, care-seeking and medication use. DESIGN: Prospective cohort study. SETTING: One pre-professional ballet school, two pre-professional university dance programs, and a professional ballet company. PARTICIPANTS: Male and female classical ballet and contemporary dancers. MAIN OUTCOME MEASURES: An initial questionnaire collected demographic and LBP history data. The monthly prevalence of LBP (all episodes, activity limiting episodes and chronic LBP) and impact (activity limitation, care-seeking, and medication use) was collected over a nine-month period. RESULTS: 119 dancers participated, which represented 54% of those invited. Activity limiting LBP was reported by 52% of dancers, while chronic LBP was reported by 24%. Seventeen percent of all episodes of LBP resulted in some form of dance activity being completely missed. One-third of the sample reported care-seeking and one-fifth of the sample used medication. A history of LBP was associated with activity limiting LBP (p < 0.01; adjusted odds ratio: 3.98; 95% confidence interval: 1.44, 11.00). CONCLUSIONS: LBP in dancers was common and had multiple impacts. This study reinforces the need for dancer access to healthcare professionals with expertise in evidence-based LBP prevention and management.

Non-motorized Treadmill Running Is Associated with Higher Cardiometabolic Demands Compared with Overground and Motorized Treadmill Running.

The aim of this study was to compare the cardiometabolic demands of running on a curved non-motorized treadmill (cNMT) with overground (OVR) and motorized treadmill (MOT) running. Fourteen trained male (n = 7) and female (n = 7) runners ([Formula: see text] 56.6 ± 4.0 mL.kg-1.min-1) participated in the study. Each experimental session consisted of 5 × 6-min bouts of running at progressively higher speeds, separated by 6-min rest (females 9-15 km.h-1; males 10.5-16.5 km.h-1). Oxygen consumption ([Formula: see text]) and heart rate (HR) during the last 2 min of each bout were measured using a portable metabolic cart. Running at a set speed on the cNMT required a higher percentage of [Formula: see text] than OVR (mean ± 90% CI, 22 ± 6%; ES ± 90% CI, 1.87 ± 0.15) and MOT (16 ± 6%; ES 1.50 ± 0.15) running. Similarly, HR during the cNMT was higher compared to OVR (25 ± 9 beats.min-1, ES 1.23 ± 0.14) and MOT (22 ± 9 beats.min-1, ES 1.35 ± 0.13) trials. The decline in running economy observed during the cNMT trial was negatively related to body mass (R2 0.493, P = 0.01), indicating lighter runners were required to work at a higher relative intensity to overcome treadmill belt resistance. These data demonstrate the higher cardiometabolic demand associated with running at a given speed on the cNMT. It is critical these differences are taken into account when prescribing training intensities on the cNMT or translating data from the laboratory to an athletic setting.

Normobaric hypoxia increases the growth hormone response to maximal resistance exercise in trained men.

This study examined the effect of hypoxia on growth hormone (GH) release during an acute bout of high-intensity, low-volume resistance exercise. Using a single-blinded, randomised crossover design, 16 resistance-trained males completed two resistance exercise sessions in normobaric hypoxia (HYP; inspiratory oxygen fraction, (FiO2) 0.12, arterial oxygen saturation (SpO2) 82 ± 2%) and normoxia (NOR; FiO2 0.21, SpO2 98 ± 0%). Each session consisted of five sets of three repetitions of 45° leg press and bench press at 85% of one repetition maximum. Heart rate, SpO2, and electromyographic activity (EMG) of the vastus lateralis muscle were measured throughout the protocol. Serum lactate and GH levels were determined pre-exposure, and at 5, 15, 30 and 60 min post-exercise. Differences in mean and integrated EMG between HYP and NOR treatments were unclear. However, there was an important increase in the peak levels and area under the curve of both lactate (HYP 5.8 ± 1.8 v NOR 3.9 ± 1.1 mmol.L-1 and HYP 138.7 ± 33.1 v NOR 105.8 ± 20.8 min.mmol.L-1) and GH (HYP 4.4 ± 3.1 v NOR 2.1 ± 2.5 ng.mL-1 and HYP 117.7 ± 86.9 v NOR 72.9 ± 85.3 min.ng.mL-1) in response to HYP. These results suggest that performing high-intensity resistance exercise in a hypoxic environment may provide a beneficial endocrine response without compromising the neuromuscular activation required for maximal strength development.

Life history and point prevalence of low back pain in pre-professional and professional dancers.

OBJECTIVES: To investigate lifetime history and point prevalence of low back pain (LBP) in pre-professional and professional dancers and to identify any demographic or physical factors associated with LBP in dancers. DESIGN: Cross-sectional study. SETTING: One pre-professional ballet school, two pre-professional university dance programs, and a professional nationally touring ballet company. PARTICIPANTS: Male and female classical ballet and contemporary dancers aged 12 years old and above. MAIN OUTCOME MEASURES: Lifetime history and point prevalence of LBP. RESULTS: A total of 110 (n = 19 male) dancers (mean (SD) 17.8 (2.9) years old) participated in the study, which represented 50% of the population invited to participate. A 74% lifetime prevalence of LBP was reported by dancers. Point and 12 month prevalence were 24 and 64%, respectively. No significant association was observed between LBP and any demographic or physical variables. CONCLUSION: Pre-professional and professional dancers have an increased vulnerability to LBP. The development of LBP within this population is complex and may not be associated with individual factors measured in this study.

Comparison of energy expenditure and heart rate responses between three commercial group fitness classes.

OBJECTIVES: The objectives of this study were to compare the energy expenditure and heart rate responses between three commercial group fitness classes (group resistance exercise [PUMP]; indoor stationary cycling [RIDE]; and step aerobics [STEP]). DESIGN: One-Way Repeated Measures incorporating a Latin Square Design for class randomisation. METHODS: Ten participants (5 males and 5 females) completed each group fitness class in random order with energy expenditure and heart rate determined using an Actiheart monitor. RESULTS: STEP and RIDE produced significantly (p<0.05) higher average heart rates (HRavg) (85.8±5.1% and 86.4±4.3% of HRmax, respectively) compared to PUMP (73.7±7% of HRmax). HRpeak was also significantly (p<0.05) higher in STEP and RIDE (97.1±4.7% and 95.6±4.5% of HRmax, respectively) when compared with the PUMP class (90±5.9% of HRmax). Total energy expenditure (TEE), both absolute and relative, were significantly (p<0.05) higher for STEP (2101.7±560.2kJ and 0.59±0.07kJkg-1min-1) and RIDE (1880.4±420kJ and 0.58±0.03kJkg-1min-1) when compared with the PUMP class (1385.1±504kJ and 0.36±0.07kJkg-1min-1). CONCLUSIONS: These data suggest that overall exercise intensity and energy expenditure was highly comparable between RIDE and STEP, which suggests these group fitness classes are more effective for developing cardiovascular fitness and assisting with weight management compared with group resistance exercise classes when performed on a regular basis.

Lower limb kinematics and physiological responses to prolonged load carriage in untrained individuals.

The aim of this study was to simultaneously assess the changes in physiology, and kinematic and spatiotemporal features of gait, during prolonged load carriage in individuals without load carriage experience. Eleven males, representative of new military recruits, walked for 120 min at 5.5 km h(- 1), 0% grade, on a motorised treadmill while carrying a 22 kg load. The load ( ≤ 30% body mass) was distributed over a weighted vest, combat webbing and replica model firearm, to reflect a patrol order load. Oxygen consumption and heart rate increased throughout the trial; however, apart from a minor increase in step length, there were no changes in the kinematic or spatiotemporal parameters, despite an increase in perceived exertion and discomfort. These data suggest that individuals with no experience in load carriage are able to maintain normal gait during 2 h of fixed speed walking, while carrying a patrol order load ≤ 30% body mass.

The relationship between workloads, physical performance, injury and illness in adolescent male football players.

BACKGROUND: The expectation that training enhances performance is well explored in professional sport. However, the additional challenges of physical and cognitive maturation may require careful consideration when determining workloads to enhance performance in adolescents. OBJECTIVE: The objective of this study was to determine the state of knowledge on the relationship between workloads, physical performance, injury and/or illness in adolescent male football players. METHODS: A systematic review of workloads, physical performance, injury and illness in male adolescent football players was conducted. Studies for this review were identified through a systematic search of six electronic databases (Academic Search Complete, CINAHL, PsycINFO, PubMed, SPORTDiscus, and Web of Science). For the purpose of this review, load was defined as the cumulative amount of stress placed on an individual from multiple training sessions and games over a period of time, expressed in terms of either the external workloads performed (e.g., resistance lifted, kilometres run) or the internal response (e.g., heart rate, rating of perceived exertion) to that workload. RESULTS: A total of 2,081 studies were initially retrieved from the six databases, of which 892 were duplicates. After screening the titles, abstracts and full texts, we identified 23 articles meeting our criteria around adolescent football players, workloads, physical performance, injury and/or illness. Seventeen articles addressed the relationship between load and physical performance, four articles addressed the relationship between load and injury and two articles addressed both. A wide range of training modalities were employed to improve the physical performance of adolescent football players, with strength training, high-intensity interval training, dribbling and small-sided games training, and a combination of these modalities in addition to normal football training, resulting in improved performances on a wide range of physiological and skill assessments. Furthermore, there was some (limited) evidence that higher workloads may be associated with the development of better physical qualities, with one study demonstrating enhanced submaximal interval shuttle run performance with each additional hour of training or game play. Of the few studies examining negative consequences associated with workloads, increases in training load led to increases in injury rates, while longer training duration was associated with a greater incidence of illness. CONCLUSION: The combined capacity for adolescent males to grow, train and improve physical performance highlights and underscores an exciting responsiveness to training in the football environment. However, the capacity to train has some established barriers for adolescents experiencing high workloads, which could also result in negative consequences. Additional research on stage-appropriate training for adolescent male footballers is required in order to address the knowledge gaps and enhance safe and efficient training practices.

Neural conduction and excitability following a simple warm up.

OBJECTIVE: This study examined the effect of a generic, active warm up on neural and muscular conduction time. DESIGN: Single group, pre-post design. METHODS: Central and peripheral neuromuscular conduction time was quantified in the abductor pollicis brevis (APB) and gastrocnemius muscles of 18 healthy participants (mean age 25.9±5.8 years, 12 males) using transcranial magnetic stimulation (TMS) and M-wave techniques, prior to and immediately following an active warm up consisting of 5 min running at 65% of maximum heart rate. Neural conduction time, for both TMS and M-wave, was quantified as the time between stimulus artefact and deflection of the wave form, whilst muscle conduction time for TMS and M-wave, was quantified from the stimulus artefact to the absolute peak twitch response. RESULTS: Following the warm up protocol, a significant reduction in muscle conduction time was found in both TMS and M-wave of 0.43 ms (P=0.02) and 0.30 ms (P=0.001) for the APB; and 0.29 ms (P<0.001) and 0.87 ms (P=0.003) for the gastrocnemius, respectively. No change was found in neural conduction using either TMS or M-wave techniques. CONCLUSIONS: These findings support previous data which demonstrate an improvement in muscular conduction time and subsequent improvement in athletic performance post warm up. The data also make evident that changes in muscular conduction time are a global response to warm up and are not directly related to muscular activity. In contrast, neural conduction time did not change and should not be confused with changes in muscular conduction time in the literature.

Predictors of academic performance of nursing and paramedic students in first year bioscience.

The expanding scope of practice of paramedics and nurses demands they possess a sophisticated knowledge of bioscience to enable them to think critically and make rational clinical decisions. It is well documented that nursing students struggle with bioscience but there are no studies examining the performance of paramedic students in this crucial subject. In this study, we compared the academic performance of first year nursing, paramedic and nursing/paramedic double degree students in a bioscience subject. Regression analyses were used to identify predictors of academic success. Data revealed a low success rate in bioscience for all three degree programs (63.2, 58.8, and 67.6% respectively) and a strong correlation between academic success in bioscience and non-bioscience subjects (r(2)=0.49). The best predictors of overall academic success were the University Admission Index score and mature entry into the course. Previous study of biology was associated with an increased bioscience and overall GPA but not with non-bioscience grades. Discriminant analysis was used to develop a model that could predict overall academic success with an accuracy of 78.5%. These criteria may be useful during the admission process and for the early identification of students at risk of failure.

Lesions of the anteroventral third ventricle region exaggerate neuroendocrine and thermogenic but not behavioral responses to a novel environment.

Mild psychological stressors provoke an acute rise in core temperature (T(C)), stimulate the hypothalamo-pituitary-adrenocortical (HPA) axis, and induce various stress-related behaviors. In the present study, we examined the effect of ablation of the anteroventral third ventricle region (AV3V) on both physiological and behavioral responses to a novel environment. T(C) was monitored in male Sprague-Dawley rats, with either sham or AV3V lesions, during a 5-h exposure to a novel environment. Trunk blood was collected, in a second group of rats, for the assessment of plasma levels of ACTH and corticosterone. Novelty-induced grooming and rearing behaviors were assessed in a third group of animals. T(C) was elevated in all animals after 30 min in the novel environment, but the rise was exaggerated in rats with AV3V lesions ( approximately 0.5 degrees C). AV3V-lesion rats maintained a higher core temperature for 2 h before it returned to the same level as the control group. Plasma levels of ACTH and corticosterone were also exaggerated in the AV3V lesion group after 30 min in a novel environment. In contrast to the physiological responses, the behavioral measures of grooming and rearing revealed no differences between the groups. The results from the current study suggest that neurons within the AV3V region exert an inhibitory influence on the HPA axis and fever developed in response to stressful psychological stimuli. They also confirm that the physiological and hormonal components of the stress response are independent of certain behavioral measures of stress.

Thermoregulatory behavior is disrupted in rats with lesions of the anteroventral third ventricular area (AV3V).

Core body temperature is maintained through a combination of physiological and behavioral effector mechanisms. While the neural pathways involved in autonomic responses to a heat stress are slowly being unraveled, those controlling behavioral responses have remained elusive. We have recently demonstrated that the tissue that surrounds the anteroventral third ventricular region (AV3V) has an important role in the autonomic response to a heat stress. The purpose of the present study was to determine the impact lesions of the AV3V have on naturally occurring thermoregulatory behaviors. Core temperature was elevated at a constant rate (0.03 degrees C/min) for 90 min using an infrared heat lamp. Animals were videotaped and scored throughout the heating protocol for grooming, escape jumps and postural extension. The frequency of escape jumps and adoption of an extended posture were significantly reduced in AV3V-lesion rats. In contrast, grooming behavior was unaffected by AV3V lesions, although heat-induced salivation was markedly attenuated. These results demonstrate that the AV3V region is pivotal in the regulation of both autonomic and behavioral thermoregulatory effector mechanisms.

Thermoregulatory role of periventricular tissue surrounding the anteroventral third ventricle (AV3V) during acute heat stress in the rat.

1. Thermoregulatory effector mechanisms are strongly influenced by hydration status. Dehydration delays the onset of evaporative heat loss and the redistribution of cardiac output in response to elevations in core temperature, yet very little is known about how and where thermal and non-thermal information is integrated. 2. The anteroventral third ventricular (AV3V) region encompasses several distinct neural structures, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus, the preoptic periventricular nucleus and the medial aspects of the medial preoptic nucleus. In addition to its well-documented role in body fluid and cardiovascular homeostasis, recent anatomical and in vitro evidence has indicated the AV3V region may also be pivotal in the integration of thermal and osmotic information. 3. Electrolytic lesions of the AV3V region produce a markedly reduced thermal tolerance in rats. Elevations in mean arterial pressure, heart rate and mesenteric resistance were all attenuated in the AV3V-lesioned animals in response to a heat stress; however, hindquarter resistance was unaffected. Heat-induced salivation was also attenuated, severely reducing the ability of rats to lose heat via evaporation. 4. The AV3V region clearly has a functional role in thermoregulation, as well as cardiovascular and body fluid homeostasis. These data add further support to the hypothesis that thermal and non-thermal information may be integrated within this region.

Lesions of the anteroventral third ventricle region (AV3V) disrupt cardiovascular responses to an elevation in core temperature.

Blood flow is redistributed from the viscera to the periphery during periods of heat stress to maximize heat loss. The heat-induced redistribution of blood flow is strongly influenced by nonthermal inputs such as hydration status. At present, little is known about where thermal and nonthermal information is integrated to generate an appropriate effector response. Recently, the periventricular tissue that surrounds the anteroventral third ventricle (AV3V) has been implicated in the integration of thermal and osmotic information. The purpose of the present study was to determine the effects of electrolytic lesions of the AV3V on the cardiovascular response to a passive heat stress in unanesthetized, free-moving male Sprague-Dawley rats. Core temperature was elevated at a constant rate of approximately 0.03 degrees C/min in sham- and AV3V-lesion rats using an infrared heat lamp. Changes in mesenteric and hindquarter vascular resistance were determined using Doppler flow probes, and heat-induced salivation was estimated using the spit-print technique. The rise in mean arterial pressure (MAP), heart rate (HR), and mesenteric resistance in response to elevations in core temperature were all attenuated in AV3V-lesion rats; however, hindquarter resistance was unaffected. Heat-induced salivation was also diminished. In addition, AV3V-lesion rats were more affected by the novelty of the experimental environment, resulting in a higher basal core temperature, HR, and MAP. These results indicate that AV3V lesions disrupt the cardiovascular and salivatory response to a passive heat stress in rats and produce an exaggerated stress-induced fever triggered by a novel environment.

Reduced thirst in old, thermally dehydrated rats.

Water intake and blood parameters of young (7-month) and old (23-month) male Brown Norway rats were assessed following a period of thermal dehydration. Rats of both ages were randomly assigned to one of three groups: (1) Unheated-blood sample, (2) Heated-blood sample, and (3) Heated-water intake. The colonic temperature of heated rats was raised at the rate of 0.05 degrees C/min for 1 h using an infrared heat lamp. Water intake was then measured over the following 2 h. The heating protocol resulted in a similar level of dehydration in both young and old rats; however, plasma osmolality and sodium concentration increased to a significant extent only in the young rats. Old rats drank significantly less water at all time points during the 2 h following the heat stress. While neither group replaced the water lost as a result of the thermal dehydration, the young rats did rehydrate to a greater extent. These results suggest that the diminished level of rehydration in aged rats, following a thermal dehydration, is due to an attenuated rise in plasma osmolality.