Identification of retinal oligomeric, citrullinated, and other tau isoforms in early and advanced AD and relations to disease status.

This study investigates various pathological tau isoforms in the retina of individuals with early and advanced Alzheimer's disease (AD), exploring their connection with disease status. Retinal cross-sections from predefined superior-temporal and inferior-temporal subregions and corresponding brains from neuropathologically confirmed AD patients with a clinical diagnosis of either mild cognitive impairment (MCI) or dementia (n = 45) were compared with retinas from age- and sex-matched individuals with normal cognition (n = 30) and non-AD dementia (n = 4). Retinal tau isoforms, including tau tangles, paired helical filament of tau (PHF-tau), oligomeric-tau (Oligo-tau), hyperphosphorylated-tau (p-tau), and citrullinated-tau (Cit-tau), were stereologically analyzed by immunohistochemistry and Nanostring GeoMx digital spatial profiling, and correlated with clinical and neuropathological outcomes. Our data indicated significant increases in various AD-related pretangle tau isoforms, especially p-tau (AT8, 2.9-fold, pS396-tau, 2.6-fold), Cit-tau at arginine residue 209 (CitR209-tau; 4.1-fold), and Oligo-tau (T22+, 9.2-fold), as well as pretangle and mature tau tangle forms like MC-1-positive (1.8-fold) and PHF-tau (2.3-fold), in AD compared to control retinas. MCI retinas also exhibited substantial increases in Oligo-tau (5.2-fold), CitR209-tau (3.5-fold), and pS396-tau (2.2-fold). Nanostring GeoMx analysis confirmed elevated retinal p-tau at epitopes: Ser214 (2.3-fold), Ser396 (2.6-fold), Ser404 (2.4-fold), and Thr231 (1.8-fold), particularly in MCI patients. Strong associations were found between retinal tau isoforms versus brain pathology and cognitive status: a) retinal Oligo-tau vs. Braak stage, neurofibrillary tangles (NFTs), and CDR cognitive scores (ρ = 0.63-0.71), b) retinal PHF-tau vs. neuropil threads (NTs) and ABC scores (ρ = 0.69-0.71), and c) retinal pS396-tau vs. NTs, NFTs, and ABC scores (ρ = 0.67-0.74). Notably, retinal Oligo-tau strongly correlated with retinal Aß42 and arterial Aß40 forms (r = 0.76-0.86). Overall, this study identifies and quantifies diverse retinal tau isoforms in MCI and AD patients, underscoring their link to brain pathology and cognition. These findings advocate for further exploration of retinal tauopathy biomarkers to facilitate AD detection and monitoring via noninvasive retinal imaging.

Identification of retinal tau oligomers, citrullinated tau, and other tau isoforms in early and advanced AD and relations to disease status.

Importance: This study identifies and quantifies diverse pathological tau isoforms in the retina of both early and advanced-stage Alzheimer's disease (AD) and determines their relationship with disease status. Objective: A case-control study was conducted to investigate the accumulation of retinal neurofibrillary tangles (NFTs), paired helical filament (PHF)-tau, oligomeric tau (oligo-tau), hyperphosphorylated tau (p-tau), and citrullinated tau (Cit-tau) in relation to the respective brain pathology and cognitive dysfunction in mild cognitively impaired (MCI) and AD dementia patients versus normal cognition (NC) controls. Design setting and participants: Eyes and brains from donors diagnosed with AD, MCI (due to AD), and NC were collected (n=75 in total), along with clinical and neuropathological data. Brain and retinal cross-sections-in predefined superior-temporal and inferior-temporal (ST/IT) subregions-were subjected to histopathology analysis or Nanostring GeoMx digital spatial profiling. Main outcomes and measure: Retinal burden of NFTs (pretangles and mature tangles), PHF-tau, p-tau, oligo-tau, and Cit-tau was assessed in MCI and AD versus NC retinas. Pairwise correlations revealed associations between retinal and brain parameters and cognitive status. Results: Increased retinal NFTs (1.8-fold, p=0.0494), PHF-tau (2.3-fold, p<0.0001), oligo-tau (9.1-fold, p<0.0001), CitR 209 -tau (4.3-fold, p<0.0001), pSer202/Thr205-tau (AT8; 4.1-fold, p<0.0001), and pSer396-tau (2.8-fold, p=0.0015) were detected in AD patients. Retinas from MCI patients showed significant increases in NFTs (2.0-fold, p=0.0444), CitR 209 -tau (3.5-fold, p=0.0201), pSer396-tau (2.6-fold, p=0.0409), and, moreover, oligo-tau (5.8-fold, p=0.0045). Nanostring GeoMx quantification demonstrated upregulated retinal p-tau levels in MCI patients at phosphorylation sites of Ser214 (2.3-fold, p=0.0060), Ser396 (1.8-fold, p=0.0052), Ser404 (2.4-fold, p=0.0018), and Thr231 (3.3-fold, p=0.0028). Strong correlations were found between retinal tau forms to paired-brain pathology and cognitive status: a) retinal oligo-tau vs. Braak stage (r=0.60, P=0.0002), b) retinal PHF-tau vs. ABC average score (r=0.64, P=0.0043), c) retinal pSer396-tau vs. brain NFTs (r=0.68, P<0.0001), and d) retinal pSer202/Thr205-tau vs. MMSE scores (r= -0.77, P=0.0089). Conclusions and Relevance: This study reveals increases in immature and mature retinal tau isoforms in MCI and AD patients, highlighting their relationship with brain pathology and cognition. The data provide strong incentive to further explore retinal tauopathy markers that may be useful for early detection and monitoring of AD staging through noninvasive retinal imaging.

Mesophotic coral bleaching associated with changes in thermocline depth.

As global temperatures continue to rise, shallow coral reef bleaching has become more intense and widespread. Mesophotic coral ecosystems reside in deeper (30-150 m), cooler water and were thought to offer a refuge to shallow-water reefs. Studies now show that mesophotic coral ecosystems instead have limited connectivity with shallow corals but host diverse endemic communities. Given their extensive distribution and high biodiversity, understanding their susceptibility to warming oceans is imperative. In this multidisciplinary study of an atoll in the Chagos Archipelago in the central Indian Ocean, we show evidence of coral bleaching at 90 m, despite the absence of shallow-water bleaching. We also show that the bleaching was associated with sustained thermocline deepening driven by the Indian Ocean Dipole, which might be further enhanced by internal waves whose influence varied at a sub-atoll scale. Our results demonstrate the potential vulnerability of mesophotic coral ecosystems to thermal stress and highlight the need for oceanographic knowledge to predict bleaching susceptibility and heterogeneity.

Fine-scale oceanographic drivers of reef manta ray (Mobula alfredi) visitation patterns at a feeding aggregation site.

Globally, reef manta rays (Mobula alfredi) are in decline and are particularly vulnerable to exploitation and disturbance at aggregation sites. Here, passive acoustic telemetry and a suite of advanced oceanographic technologies were used for the first time to investigate the fine-scale (5-min) influence of oceanographic drivers on the visitation patterns of 19 tagged M. alfredi to a feeding aggregation site at Egmont Atoll in the Chagos Archipelago. Boosted regression trees indicate that tag detection probability increased with the intrusion of cold-water bores propagating up the atoll slope through the narrow lagoon inlet during flood tide, potentially transporting zooplankton from the thermocline. Tag detection probability also increased with warmer near-surface temperature close to low tide, with near-surface currents flowing offshore, and with high levels of backscatter (a proxy of zooplankton biomass). These combinations of processes support the proposition that zooplankton carried from the thermocline into the lagoon during the flood may be pumped back out through the narrow inlet during an ebb tide. These conditions provide temporally limited feeding opportunities for M. alfredi, which are tied on the tides. Results also provide some evidence of the presence of Langmuir Circulation, which transports and concentrates zooplankton, and may partly explain why M. alfredi occasionally remained at the feeding location for longer than that two hours. Identification of these correlations provides unique insight into the dynamic synthesis of fine-scale oceanographic processes which are likely to influence the foraging ecology of M. alfredi at Egmont Atoll, and elsewhere throughout their range.

The Coping Assessment for Bereavement and Loss Experiences (CABLE): Development and initial validation.

The authors present the development and validation of the Coping Assessment for Bereavement and Loss Experiences (CABLE), the first instrument designed to assess a range of potentially constructive strategies for coping with grief following the death of a loved one. Exploratory and confirmatory factor analysis with an international sample of bereaved adults (N = 844) yielded a six-factor, 28-item structure. Use of this validated, clinically useful, self-report tool can inform clinicians and researchers in evaluating bereavement coping, and in developing interventions designed to increase the number and broaden the types of coping strategies used to facilitate healing following loss.

Gga3 deletion and a GGA3 rare variant associated with late onset Alzheimer's disease trigger BACE1 accumulation in axonal swellings.

Axonal dystrophy, indicative of perturbed axonal transport, occurs early during Alzheimer's disease (AD) pathogenesis. Little is known about the mechanisms underlying this initial sign of the pathology. This study proves that Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) loss of function, due to Gga3 genetic deletion or a GGA3 rare variant that cosegregates with late-onset AD, disrupts the axonal trafficking of the ß-site APP-cleaving enzyme 1 (BACE1) resulting in its accumulation in axonal swellings in cultured neurons and in vivo. We show that BACE pharmacological inhibition ameliorates BACE1 axonal trafficking and diminishes axonal dystrophies in Gga3 null neurons in vitro and in vivo. These data indicate that axonal accumulation of BACE1 engendered by GGA3 loss of function results in local toxicity leading to axonopathy. Gga3 deletion exacerbates axonal dystrophies in a mouse model of AD before ß-amyloid (Aß) deposition. Our study strongly supports a role for GGA3 in AD pathogenesis, where GGA3 loss of function triggers BACE1 axonal accumulation independently of extracellular Aß, and initiates a cascade of events leading to the axonal damage distinctive of the early stage of AD.

MCL1 as a Therapeutic Target in Parkinson's Disease?

Dopamine neurons in the substantia nigra (SN) pars compacta are selectively lost during the progression of Parkinson's disease (PD). Recent work performed on the role of the Bcl2 family (highly specialized proteins which control cellular survival and death) in midbrain dopamine neurons has led to the identification of the Bcl2 factor Mcl1 as a weak link in the survival of these neurons. We hypothesize that the regulation of BCL2 proteins may explain this selective vulnerability, and may even provide a novel therapeutic opportunity - strengthening weak links such as MCL1 could result in a delay or complete abrogation of cell death during PD.

Hyperthermia-induced seizures followed by repetitive stress are associated with age-dependent changes in specific aspects of the mouse stress system.

Stress is among the most frequently self-reported factors provoking epileptic seizures in children and adults. It is still unclear, however, why some people display stress-sensitive seizures and others do not. Recently, we showed that young epilepsy patients with stress-sensitive seizures exhibit a dysregulated hypothalamic-pituitary-adrenal (HPA)-axis. Most likely, this dysregulation gradually develops, and is triggered by stressors occurring early in life (early-life stress [ELS]). ELS may be particularly impactful when overlapping with the period of epileptogenesis. To examine this in a controlled and prospective manner, the present study investigated the effect of repetitive variable stressors or control treatment between postnatal day (PND) 12 and 24 in male mice exposed on PND10 to hyperthermia (HT)-induced prolonged seizures (control: normothermia). A number of peripheral and central indices of HPA-axis activity were evaluated at pre-adolescent and young adult age (ie, at PND25 and 90, respectively). At PND25 but not at PND90, body weight gain and absolute as well as relative (to body weight) thymus weight were reduced by ELS (vs control), whereas relative adrenal weight was enhanced, confirming the effectiveness of the stress treatment. Basal and stress-induced corticosterone levels were unaffected, though, by ELS at both ages. HT by itself did not affect any of these peripheral markers of HPA-axis activity, nor did it interact with ELS. However, centrally we did observe age-specific interaction effects of HT and ELS with regard to hippocampal glucocorticoid receptor mRNA expression, neurogenesis with the immature neurone marker doublecortin and the number of hilar (ectopic) granule cells using Prox1 staining. This lends some support to the notion that exposure to repetitive stress after HT-induced seizures may dysregulate central components of the stress system in an age-dependent manner. Such dysregulation could be one of the mechanisms conferring higher vulnerability of individuals with epilepsy to develop seizures in the face of stress.

Survival of midbrain dopamine neurons depends on the Bcl2 factor Mcl1.

Mitochondria-dependent apoptosis plays an important role in the embryonic development of the midbrain dopaminergic system as well as in Parkinson's disease. Central to mitochondria-dependent apoptosis is the Bcl2 family of apoptosis-regulating proteins. However, it was unclear which Bcl2 proteins are important for the survival of dopaminergic neurons. Here, we identify Mcl1 as a critical Bcl2 pro-survival factor in midbrain dopaminergic neurons. Using a chemical biology approach to inhibit various components of the apoptotic machinery in the dopaminergic MN9D cell line or the control neuroblastoma N2A cell line, we find that functional inhibition of Mcl1 with the high affinity small molecule inhibitor UMI-77 results in a rapid and dose-dependent loss of viability, selectively in dopaminergic cells. In-depth analysis of the apoptotic signaling pathway reveals that chemical inhibition of Mcl1 results in the activation of Bax, activation of cleaved caspase-3 and finally cell death. The dependence of mouse dopaminergic midbrain neurons on Mcl1 was confirmed using ex vivo slice cultures from Pitx3GFP/+ and wildtype mice. In mouse dopaminergic midbrain neurons positive for the midbrain dopaminergic marker Pitx3, or tyrosine hydroxylase, UMI-77 treatment caused a dramatic increase in cleaved caspase 3, indicating that Mcl1 activity is required for basal neuronal survival. Overall, our results suggest that Mcl1 is of critical importance to dopaminergic neurons and is a weak link in the chain controlling cellular survival. Boosting the pro-survival function of Mcl1 should be pursued as a therapeutic approach to augment the resilience of midbrain dopaminergic neurons to apoptotic stress in Parkinson's disease.

Job satisfaction is more than a fruit basket, health checks and free exercise: Cross-sectional study among 10,000 wage earners.

AIM: Workers who are satisfied with their job are the cornerstones of healthy and productive companies. This study investigated factors associated with job satisfaction in the general working population. METHODS: From the 2010 round of the Danish Work Environment Cohort Study, currently employed wage earners ( N=10,427) replied to questions about work, lifestyle and health. Multinomial logistic regression controlled for sex, age, job group, smoking, body mass index, chronic disease and general health assessed the association between work factors and job satisfaction (very satisfied and satisfied, respectively, with unsatisfied as reference). RESULTS: Psychosocial work factors - social support from superiors, social support from colleagues and influence at work - had the strongest association with job satisfaction. For example, for high social support from superiors, the odds ratio (OR) for being very satisfied with the job was 12.35 (95% confidence interval [CI] 8.71-17.51). With sedentary work as reference, the OR for being very satisfied with the job for 'standing and walking work that is not strenuous' was 1.57 (95% CI 1.06-2.33), while the opposite was seen for 'heavy and strenuous work' with an OR of 0.34 (95% CI 0.18-0.62). Only two out of five types of workplace health-promotion offers (physical exercise and healthy diet) were associated with job satisfaction. For example, for offers of physical exercise the OR for being very satisfied with the job was 1.84 (95% CI 1.33-2.55). CONCLUSIONS: While psychosocial work factors and to some extent physical work demands are important for job satisfaction, workplace health-promotion offers appear to play a minor role.

The Dmax method is a valid procedure to estimate physical working capacity at fatigue threshold.

INTRODUCTION: The purpose of this study was to determine the validity of the maximal distance-electromyography (Dmax-EMG) method for estimating physical working capacity at fatigue threshold (PWCFT ). METHODS: Twenty-one men and women (age 22.9 ± 3.0 years) volunteered to perform 12 sessions of high-intensity interval training (HIIT) over 4 weeks. Before and after HIIT training, a graded exercise test (GXT) was used to estimate PWCFT using the Dmax method and the original (ORG) method. RESULTS: There was a significant increase in PWCFT for both ORG (+10.6%) and Dmax (+12.1%) methods, but no significant difference in the change values between methods. Further, Bland-Altman analyses resulted in non-significant biases (ORG-Dmax) between methods at pre-HIIT (-6.4 ± 32.5 W; P > 0.05) and post-HIIT (-4.2 ± 33.1 W; P > 0.05). CONCLUSION: The Dmax method is sensitive to training and is a valid method for estimating PWCFT in young men and women. Muscle Nerve 55: 344-349, 2017.

Results from 10 Years of a CBT Pain Self-Management Outpatient Program for Complex Chronic Conditions.

Background. Traditional unimodal interventions may be insufficient for treating complex pain, as they do not address cognitive and behavioural contributors to pain. Cognitive Behavioural Therapy (CBT) and physical exercise (PE) are empirically supported treatments that can reduce pain and improve quality of life. Objectives. To examine the outcomes of a pain self-management outpatient program based on CBT and PE at a rehabilitation hospital in Toronto, Ontario. Methods. The pain management group (PMG) consisted of 20 sessions over 10 weeks. The intervention consisted of four components: education, cognitive behavioural skills, exercise, and self-management strategies. Outcome measures included the sensory, affective, and intensity of pain experience, depression, anxiety, pain disability, active and passive coping style, and general health functioning. Results. From 2002 to 2011, 36 PMGs were run. In total, 311 patients entered the program and 214 completed it. Paired t-tests showed significant pre- to posttreatment improvements in all outcomes measured. Patient outcomes did not differ according to the number or type of diagnoses. Both before and after treatment, women reported more active coping than men. Discussion. The PMGs improved pain self-management for patients with complex pain. Future research should use a randomized controlled design to better understand the outcomes of PMGs.

Reductions in biomarkers of exposure, impacts on smoking urge and assessment of product use and tolerability in adult smokers following partial or complete substitution of cigarettes with electronic cigarettes.

BACKGROUND: Electronic cigarettes (e-cigarettes) are popular alternatives to conventional cigarettes among adult smokers wishing to reduce their exposure to harmful smoke constituents. However, little information exists on the relative internal exposures resulting from the exclusive or dual use of e-cigarettes. METHODS: Measurements of product use; adverse events; changes in smoking urge; and blood, urine and exhaled breath biomarkers of exposure (BoE) representing toxicants believed to contribute to smoking related diseases were made at baseline and after five days of product use in 105 clinically-confined smokers randomized into groups that partially or completely substituted their usual brand combustible cigarette with commercial e-cigarettes, or discontinued all nicotine and tobacco products. RESULTS: Subjects switching to e-cigarettes had significantly lower levels (29 %-95 %) of urinary BoEs after 5 days. Nicotine equivalents declined by 25 %-40 %. Dual users who substituted half of their self-reported daily cigarette consumption with e-cigarettes experienced 7 %-38 % reductions, but had increases (1 %-20 %) in nicotine equivalents. Blood nicotine biomarker levels were lower in the cessation (75 %-96 %) and e-cigarette use groups (11 %-83 %); dual users had no significant reductions. All groups experienced significant decreases in exhaled CO (27 %-89 %). Exhaled NO increases (46 %-63 %) were observed in the cessation and e-cigarette use groups; dual users had minimal changes. By Day 5, all groups had greater reductions in smoking urge compared to cessation. However, reductions were larger in the dual use group. No serious adverse events were observed. CONCLUSIONS: Exposures to harmful smoke toxicants were observed to be lower in smokers who completely or partially replaced their cigarettes with e-cigarettes over five days.

Intramuscular MAPK signaling following high volume and high intensity resistance exercise protocols in trained men.

PURPOSE: To examine the mitogen-activated protein kinase (MAPK) family of signaling proteins following typical high volume (HV) and high intensity (HI) lower body resistance exercise protocols in resistance-trained men. METHODS: Ten resistance-trained men (24.7 ± 3.4 year; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm) performed each resistance exercise protocol in a random, counterbalanced order. The HV protocol utilized a load of 70 % 1-RM for sets of 10-12 repetitions with a 1-min rest period length between sets and exercises. The HI protocol utilized a load of 90 % 1-RM for sets of 3-5 repetitions with a 3-min rest period length between sets and exercises. Both protocols included six sets of barbell back squats and four sets of bilateral leg press, bilateral hamstring curls, bilateral leg extensions, and seated calf raises. Fine needle muscle biopsies of the vastus lateralis were completed at baseline (BL) and 1-h post exercise (1H). RESULTS: No significant differences over time were noted for phosphorylation of MEK1, ERK1/2, p38, MSK1, ATF2, p53, or c-Jun (p > 0.05). No significance between trial interactions was noted for phosphorylation of MAPK signaling proteins, including MEK1, ERK1/2, p38, JNK, MSK1, ATF2, STAT1, p53, c-Jun, or HSP27 (p > 0.05). However, significant time effects were observed for phosphorylation of JNK (p < 0.01), HSP27 (p < 0.01), and STAT1 (p = 0.03). Phosphorylation of JNK, HSP27, and STAT1 was significantly elevated from BL at 1H for both HV and HI. CONCLUSIONS: HV and HI lower body resistance exercise protocols appear to elicit similar MAPK activation in resistance-trained men.

Hepatitis B Reverse Seroconversion and Transmission in a Hemodialysis Center: A Public Health Investigation and Case Report.

In March 2013, public health authorities were notified of a new hepatitis B virus (HBV) infection in a patient receiving hemodialysis. We investigated to identify the source and prevent additional infections. We reviewed medical records, interviewed the index patient regarding hepatitis B risk factors, performed HBV molecular analysis, and observed infection control practices at the outpatient hemodialysis facility where she received care. The index patient's only identified hepatitis B risk factor was hemodialysis treatment. The facility had no other patients with known active HBV infection. One patient had evidence of a resolved HBV infection. Investigation of this individual, who was identified as the source patient, indicated that HBV reverse seroconversion and reactivation had occurred in the setting of HIV (human immunodeficiency virus) infection and a failed kidney transplant. HBV whole genome sequences analysis from the index and source patients indicated 99.9% genetic homology. Facility observations revealed multiple infection control breaches. Inadequate dilution of the source patient's sample during HBV testing might have led to a false-negative result, delaying initiation of hemodialysis in isolation. In conclusion, HBV transmission occurred after an HIV-positive hemodialysis patient with transplant-related immunosuppression experienced HBV reverse seroconversion and reactivation. Providers should be aware of this possibility, especially among severely immunosuppressed patients, and maintain stringent infection control.

Comparative mRNA analysis of behavioral and genetic mouse models of aggression.

Mouse models of aggression have traditionally compared strains, most notably BALB/cJ and C57BL/6. However, these strains were not designed to study aggression despite differences in aggression-related traits and distinct reactivity to stress. This study evaluated expression of genes differentially regulated in a stress (behavioral) mouse model of aggression with those from a recent genetic mouse model aggression. The study used a discovery-replication design using two independent mRNA studies from mouse brain tissue. The discovery study identified strain (BALB/cJ and C57BL/6J) × stress (chronic mild stress or control) interactions. Probe sets differentially regulated in the discovery set were intersected with those uncovered in the replication study, which evaluated differences between high and low aggressive animals from three strains specifically bred to study aggression. Network analysis was conducted on overlapping genes uncovered across both studies. A significant overlap was found with the genetic mouse study sharing 1,916 probe sets with the stress model. Fifty-one probe sets were found to be strongly dysregulated across both studies mapping to 50 known genes. Network analysis revealed two plausible pathways including one centered on the UBC gene hub which encodes ubiquitin, a protein well-known for protein degradation, and another on P38 MAPK. Findings from this study support the stress model of aggression, which showed remarkable molecular overlap with a genetic model. The study uncovered a set of candidate genes including the Erg2 gene, which has previously been implicated in different psychopathologies. The gene networks uncovered points at a Redox pathway as potentially being implicated in aggressive related behaviors.

Effects of 4 Weeks of High-Intensity Interval Training and ß-Hydroxy-ß-Methylbutyric Free Acid Supplementation on the Onset of Neuromuscular Fatigue.

This study investigated the effects of high-intensity interval training (HIIT) and ß-hydroxy-ß-methylbutyric free acid (HMB) supplementation on physical working capacity at the onset of neuromuscular fatigue threshold (PWC(FT)). Thirty-seven participants (22 men, 15 women; 22.8 ± 3.4 years) completed an incremental cycle ergometer test (graded exercise test [GXT]); electromyographic amplitude from the right vastus lateralis was recorded. Assessments occurred preceding (PRE) and after 4 weeks of supplementation (POST). Participants were randomly assigned to control (C, n = 9), placebo (P, n = 14), or supplementation (S, n = 14) groups. Both P and S completed 12 HIIT sessions, whereas C maintained normal diet and activity patterns. The PWC(FT) (W) was determined using the maximal perpendicular distance (D(MAX)) method. Electromyographic amplitude (µVrms) over time was used to generate a cubic regression. Onset of fatigue (TF) was the x-value of the point on the regression that was at D(MAX) from a line between the first and last data points. The PWC(FT) was estimated using TF and GXT power-output increments. The 2-way analysis of variance (ANOVA) (group × time) resulted in a significant interaction for PWC(FT) (F = 6.69, p = 0.004). Post hoc analysis with 1-way ANOVA resulted in no difference in PWC(FT) among groups at PRE (F = 0.87, p = 0.43); however, a difference in PWC(FT) was shown for POST (F = 5.46, p = 0.009). Post hoc analysis among POST values revealed significant differences between S and both P (p = 0.034) and C (p = 0.003). No differences (p = 0.226) were noted between P and C. Paired samples t-tests detected significant changes after HIIT for S (p < 0.001) and P (p = 0.016), but no change in C (p = 0.473). High-intensity interval training increased PWC(FT), but HMB with HIIT was more effective than HIIT alone. Furthermore, it seems that adding HMB supplementation with HIIT in untrained men and women may further improve endurance performance measures.

Intramuscular anabolic signaling and endocrine response following high volume and high intensity resistance exercise protocols in trained men.

Resistance exercise paradigms are often divided into high volume (HV) or high intensity (HI) protocols, however, it is unknown whether these protocols differentially stimulate mTORC1 signaling. The purpose of this study was to examine mTORC1 signaling in conjunction with circulating hormone concentrations following a typical HV and HI lower-body resistance exercise protocol. Ten resistance-trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm) performed each resistance exercise protocol in a random, counterbalanced order. Blood samples were obtained at baseline (BL), immediately (IP), 30 min (30P), 1 h (1H), 2 h (2H), and 5 h (5H) postexercise. Fine needle muscle biopsies were completed at BL, 1H, and 5H. Electromyography of the vastus lateralis was also recorded during each protocol. HV and HI produced a similar magnitude of muscle activation across sets. Myoglobin and lactate dehydrogenase concentrations were significantly greater following HI compared to HV (P = 0.01-0.02), whereas the lactate response was significantly higher following HV compared to HI (P = 0.003). The growth hormone, cortisol, and insulin responses were significantly greater following HV compared to HI (P = 0.0001-0.04). No significant differences between protocols were observed for the IGF-1 or testosterone response. Intramuscular anabolic signaling analysis revealed a significantly greater (P = 0.03) phosphorylation of IGF-1 receptor at 1H following HV compared to HI. Phosphorylation status of all other signaling proteins including mTOR, p70S6k, and RPS6 were not significantly different between trials. Despite significant differences in markers of muscle damage and the endocrine response following HV and HI, both protocols appeared to elicit similar mTORC1 activation in resistance-trained men.

Resistance training improves capacity to delay neuromuscular fatigue in older adults.

The purpose of this study was to investigate the effects of short term resistance exercise on neuromuscular fatigue threshold (PWCFT), strength, functional performance, and body composition in older adults. Twenty-three participants (71.2 ± 6.0 yr) were randomly assigned to 6 weeks of resistance exercise (EXE) or control (CONT). A submaximal cycle ergometer test, physical working capacity at fatigue threshold, was used to determine PWCFT. Strength was assessed with predicted leg extension 1-RM and functional performance with time to complete 5 chair rises (CHAIR) and walk an 8-ft course (WALK). PWCFT, 1-RM and CHAIR significantly (p<0.05) improved in the EXE (27%, 24%, 27%) compared with CONT (-0.1%, 7%, 6%), respectively. The results of this study suggest that short term EXE improved strength, functionality and the capacity to delay the onset of neuromuscular fatigue in older adults.