Comparison of Force, Neuromuscular, and Metabolic Responses During Sustained, Isometric Handgrip Holds to Failure Anchored to Low and High Perceptual Intensities in Men: An Exploratory Study.

ABSTRACT: Kwak, M, Succi, PJ, Benitez, B, Mitchinson, C, Samaan, MA, Abel, MG, and Bergstrom, HC. Comparison of force, neuromuscular, and metabolic responses during sustained, isometric handgrip holds to failure anchored to low and high perceptual intensities in men: An exploratory study. J Strength Cond Res 38(8): e405-e416, 2024-This study examined the responses of force alterations, relative to critical force (CF), neuromuscular parameters, and muscle oxygenation (SmO2) for isometric handgrip holds to failure (HTF) anchored to ratings of perceived exertion (RPE) of 3 and 7. Twelve men completed pre-maximal voluntary isometric contractions (pre-MVIC), submaximal HTF at 4 percentages of pre-MVIC, HTF at RPE = 3 and 7, and post-MVIC. Mechanomyograpic (MMG) signals and SmO2 were recorded during the RPE HTF. Analyses included paired-samples t-tests and repeated-measures ANOVAs at an alpha level of p ≤ 0.05. Time to task failure was not different between RPE 3 (478.7 ± 196.6 s) and RPE 7 (495.8 ± 173.8 s). Performance fatigability (PF) and MMG amplitude (AMP) were greater for RPE 7 (PF: 37.9 ± 12.9%; MMG AMP: 15.7 ± 7.4% MVIC) than RPE 3 (PF: 30.0 ± 14.5%; MMG AMP: 10.2 ± 6.5% MVIC), but MMG mean power frequency (MPF) was greater for RPE 3 (146.2 ± 31.1% MVIC) than RPE 7 (128.8 ± 23.0% MVIC). There were RPE-dependent decreases in force (p ≤ 0.01) across 3 discernable phases during the HTF. There were decreases in MMG AMP across time for both RPEs, but there were no significant changes in MMG MPF or SmO2. There were overall similar motor unit control strategies and local metabolic demand between RPEs. The majority of the HTF performed below CF at RPE 3 and 7 indicated CF did not reflect the highest sustainable force. When prescribing isometric exercise anchored to RPE, practitioners should be aware of the magnitude of force loss and relative intensity of the task to be sure desired training loads are met.

Sling and Forget It? A Systematic Review of Operative versus Non-Operative Outcomes for Scapula Fractures.

BACKGROUND: The majority of scapula fractures have historically been treated non-operatively. The current literature describing patient outcomes following scapula fractures is limited. Our objective was to determine differences in outcomes between operatively and non-operatively treated scapular fractures. The goal of our study was to provide an updated and comprehensive systematic review for scapula body, neck, and glenoid fractures focusing on several outcomes including union rate, return to work, pain, shoulder active range of motion, strength, functional scores, and any recorded complications. METHODS: The PRISMA methodology was followed for this systematic review. Articles were obtained from the PubMed/Medline database using the following search terms: scapula body OR scapula neck OR intra-articular glenoid AND fracture. Additional articles were obtained by searching the bibliographies of included references. Studies were included if they contained clinical data on one or more of our study objectives and contained participants with a scapular body, neck, and/or glenoid fracture who were at least 16 years old. A total of 35 papers, with 822 total cases were included. Studies chosen were assessed for level of evidence and reviewed for data pertaining to the current study objectives. All cases of scapula fractures found throughout the literature were analyzed for outcome data. Outcomes studied included union rate, return to work, pain, shoulder active range of motion, strength, functional scores, and recorded complications. RESULTS: The overwhelming majority of scapula fractures go on to union. The majority of patients will eventually return to work. Persistent post-injury pain is unfortunately common. Shoulder range of motion and strength are decreased when compared to the contralateral shoulder. Non-operative glenoid fractures have the lowest reported functional scores. Malunion, need for additional surgeries, and post-traumatic arthritis were the most common complications. CONCLUSION: When treating scapula fractures, orthopedic surgeons must consider the specific fracture pattern, as well as patient specific goals. Risks and benefits of both operative and non-operative management should be discussed with the patient including the exceptionally low non-union rate regardless of treatment option and that persistent pain following injury is unfortunately common.

Force and Neuromuscular Responses During a Handgrip Hold to Failure Anchored to a Moderate Perceptual Intensity in Males.

OBJECTIVES: The current study investigated performance fatigability (PF) and time course of changes in force, electromyographic amplitude (EMG AMP) and frequency (EMG MPF), and neuromuscular efficiency (NME) during a sustained, isometric, handgrip hold to failure (HTF) using the rating of perceived exertion (RPE)-Clamp Model. METHODS: Twelve males performed a handgrip HTF anchored to RPE=5. The time to task failure (Tlim), force (N), EMG AMP and MPF, and NME (normalized force/ normalized EMG AMP) were recorded. Analyses included a paired samples t-test for PF at an alpha of p<0.05, 1-way repeated measures ANOVA across time and post-hoc t-tests (p<0.0025) for force, EMG AMP and MPF, and NME responses. RESULTS: The PF (pre- to post- maximal force % decline) was 38.2±11.5%. There were decreases in responses, relative to 0% Tlim, from 40% to 100% Tlim (force), at 30%, 60%, and 100% Tlim (EMG AMP), from 10% to 100% Tlim(EMP MPF), and from 50% to 65%, and 80% to 100% Tlim (NME) (p<0.0025). CONCLUSIONS: The RPE-Clamp Model in this study demonstrated that pacing strategies may be influenced by the integration of anticipatory, feedforward, and feedback mechanisms, and provided insights into the relationship between neuromuscular and perceptual responses, and actual force generating capacity.

Influence of Blood Flow Restriction on Neuromuscular Function and Fatigue During Forearm Flexion in Men.

ABSTRACT: Montgomery, TR Jr, Olmos, A, Sears, KN, Succi, PJ, Hammer, SM, Bergstrom, HC, Hill, EC, Trevino, MA, and Dinyer-McNeely, TK. Influence of blood flow restriction on neuromuscular function and fatigue during forearm flexion in men. J Strength Cond Res 38(7): e349-e358, 2024-To determine the effects of blood flow restriction (BFR) on the mean firing rate (MFR) and motor unit action potential amplitude (MUAPAMP) vs. recruitment threshold (RT) relationships during fatiguing isometric elbow flexions. Ten men (24.5 ± 4.0 years) performed isometric trapezoidal contractions at 50% maximum voluntary contraction to task failure with or without BFR, on 2 separate days. For BFR, a cuff was inflated to 60% of the pressure required for full brachial artery occlusion at rest. During both visits, surface electromyography was recorded from the biceps brachii of the dominant limb and the signal was decomposed. A paired-samples t test was used to determine the number of repetitions completed between BFR and CON. ANOVAs (repetition [first, last] × condition [BFR, CON]) were used to determine differences in MFR vs. RT and MUAPAMP vs. RT relationships. Subjects completed more repetitions during CON (12 ± 4) than BFR (9 ± 2; p = 0.012). There was no significant interaction (p > 0.05) between the slopes and y-intercepts during the repetition × condition interaction for MUAPAMP vs. MFR. However, there was a main effect of repetition for the slopes of the MUAPAMP vs. RT (p = 0.041) but not the y-intercept (p = 0.964). Post hoc analysis (collapsed across condition) indicated that the slopes of the MUAPAMP vs. RT during the first repetition was less than the last repetition (first: 0.022 ± 0.003 mv/%MVC; last: 0.028 ± 0.004 mv/%MVC; p = 0.041). Blood flow restriction resulted in the same amount of higher threshold MU recruitment in approximately 75% of the repetitions. Furthermore, there was no change in MFR for either condition, even when taken to task failure. Thus, BFR training may create similar MU responses with less total work completed than training without BFR.

Glial activation in pain and emotional processing regions in the nitroglycerin mouse model of chronic migraine.

OBJECTIVE: Our aim was to survey astrocyte and microglial activation across four brain regions in a mouse model of chronic migraine. BACKGROUND: Chronic migraine is a leading cause of disability, with higher rates in females. The role of central nervous system neurons and glia in migraine pathophysiology is not fully elucidated. Preclinical studies have shown abnormal glial activation in the trigeminal nucleus caudalis of male rodents. No current reports have investigated glial activation in both sexes in other important brain regions involved with the nociceptive and emotional processing of pain. METHODS: The mouse nitroglycerin model of migraine was used, and nitroglycerin (10 mg/kg) or vehicle was administered every other day for 9 days. Prior to injections on days 1, 5, and 9, cephalic allodynia was determined by periorbital von Frey hair testing. Immunofluorescent staining of astrocyte marker, glial fibrillary protein (GFAP), and microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), in male and female trigeminal nucleus caudalis, periaqueductal gray, somatosensory cortex, and nucleus accumbens was completed. RESULTS: Behavioral testing demonstrated increased cephalic allodynia in nitroglycerin- versus vehicle-treated mice. An increase in the percent area covered by GFAP+ cells in the trigeminal nucleus caudalis and nucleus accumbens, but not the periaqueductal gray or somatosensory cortex, was observed in response to nitroglycerin. No significant differences were observed for Iba1 staining across brain regions. We did not detect significant sex differences in GFAP or Iba1 quantification. CONCLUSIONS: Immunohistochemical analysis suggests that, at the time point tested, immunoreactivity of GFAP+ astrocytes, but not Iba1+ microglia, changes in response to chronic migraine-associated pain. Additionally, there do not appear to be significant differences between males and females in GFAP+ or Iba1+ cells across the four brain regions analyzed.

Rational adaptation in word production: Strong conceptual ability reduces the effect of lexical impairments on verb retrieval in aphasia.

Language users rely on both linguistic and conceptual processing abilities to efficiently comprehend or produce language. According to the principle of rational adaptation, the degree to which a cognitive system relies on one process vs. another can change under different conditions or disease states with the goal of optimizing behavior. In this study, we investigated rational adaptation in reliance on linguistic versus conceptual processing in aphasia, an acquired disorder of language. In individuals living with aphasia, verb-retrieval impairments are a pervasive deficit that negatively impacts communicative function. As such, we examined evidence of adaptation in verb production, using parallel measures to index impairment in two of verb naming's critical subcomponents: conceptual and linguistic processing. These component processes were evaluated using a standardized assessment battery designed to contrast non-linguistic (picture input) and linguistic (word input) tasks of conceptual action knowledge. The results indicate that non-linguistic conceptual action processing can be impaired in people with aphasia and contributes to verb-retrieval impairments. Furthermore, relatively unimpaired conceptual action processing can ameliorate the influence of linguistic processing deficits on verb-retrieval impairments. These findings are consistent with rational adaptation accounts, indicating that conceptual processing plays a key role in language function and can be leveraged in rehabilitation to improve verb retrieval in adults with chronic aphasia.

Genetic evidence for functional diversification of gram-negative intermembrane phospholipid transporters.

The outer membrane of gram-negative bacteria is a barrier to chemical and physical stress. Phospholipid transport between the inner and outer membranes has been an area of intense investigation and, in E. coli K-12, it has recently been shown to be mediated by YhdP, TamB, and YdbH, which are suggested to provide hydrophobic channels for phospholipid diffusion, with YhdP and TamB playing the major roles. However, YhdP and TamB have different phenotypes suggesting distinct functions. It remains unclear whether these functions are related to phospholipid metabolism. We investigated a synthetic cold sensitivity caused by deletion of fadR, a transcriptional regulator controlling fatty acid degradation and unsaturated fatty acid production, and yhdP, but not by ΔtamB ΔfadR or ΔydbH ΔfadR. Deletion of tamB recuses the ΔyhdP ΔfadR cold sensitivity further demonstrating the phenotype is related to functional diversification between these genes. The ΔyhdP ΔfadR strain shows a greater increase in cardiolipin upon transfer to the non-permissive temperature and genetically lowering cardiolipin levels can suppress cold sensitivity. These data also reveal a qualitative difference between cardiolipin synthases in E. coli, as deletion of clsA and clsC suppresses cold sensitivity but deletion of clsB does not. Moreover, increased fatty acid saturation is necessary for cold sensitivity and lowering this level genetically or through supplementation of oleic acid suppresses the cold sensitivity of the ΔyhdP ΔfadR strain. Together, our data clearly demonstrate that the diversification of function between YhdP and TamB is related to phospholipid metabolism. Although indirect regulatory effects are possible, we favor the parsimonious hypothesis that YhdP and TamB have differential phospholipid-substrate transport preferences. Thus, our data provide a potential mechanism for independent control of the phospholipid composition of the inner and outer membranes in response to changing conditions based on regulation of abundance or activity of YhdP and TamB.

No sex differences in time-to-task failure and neuromuscular patterns of response during submaximal, bilateral, isometric leg extensions.

BACKGROUND: In general, it has been suggested that females are more fatigue-resistant than males, with the magnitude of difference being most pronounced during low-intensity sustained contractions. However, the mechanisms for the apparent sex difference have not yet been fully elucidated in the literature. This study aimed to examine sex-related differences in fatigability and patterns of neuromuscular responses for surface electromyographic (sEMG) and mechanomyographic (sMMG) amplitude and frequency (MPF) characteristics during a sustained submaximal bilateral, isometric leg extension muscle action. METHODS: A sample of 20 young recreationally active males and females with previous resistance training experience performed a sustained, submaximal, bilateral isometric leg extension until task failure. Time-to-task failure was compared using a nonparametric bootstrap of the 95% confidence interval for the mean difference between males and females. Additionally, patterns of response for sEMG and sMMG amplitude and MPF of the dominant limb were examined using linear mixed effect models. RESULTS: There were no differences in time-to-task failure between males and females. Additionally, neuromuscular responses revealed similar patterns of responses between males and females. Interestingly, sEMG amplitude and sMMG amplitude and MPF all revealed non-linear responses, while sEMG MPF demonstrated linear responses. CONCLUSION: These data revealed that time-to-task failure was not different between males and females during sustained submaximal bilateral, isometric leg extension. Interestingly, the parallel, non-linear, increases in sEMG and sMMG amplitude may indicate fatigue induced increases in motor unit recruitment, while the parallel decreases in sMMG MPF may be explained by the intrinsic properties of later recruited motor units, which may have inherently lower firing rates than those recruited earlier.

Valproic Acid Causes Redox-Regulated Post-Translational Protein Modifications That Are Dependent upon P19 Cellular Differentiation States.

Valproic acid (VPA) is a common anti-epileptic drug and known neurodevelopmental toxicant. Although the exact mechanism of VPA toxicity remains unknown, recent findings show that VPA disrupts redox signaling in undifferentiated cells but has little effect on fully differentiated neurons. Redox imbalances often alter oxidative post-translational protein modifications and could affect embryogenesis if developmentally critical proteins are targeted. We hypothesize that VPA causes redox-sensitive post-translational protein modifications that are dependent upon cellular differentiation states. Undifferentiated P19 cells and P19-derived neurons were treated with VPA alone or pretreated with D3T, an inducer of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway, prior to VPA exposure. Undifferentiated cells treated with VPA alone exhibited an oxidized glutathione redox couple and increased overall protein oxidation, whereas differentiated neurons were protected from protein oxidation via increased S-glutathionylation. Pretreatment with D3T prevented the effects of VPA exposure in undifferentiated cells. Taken together, our findings support redox-sensitive post-translational protein alterations in undifferentiated cells as a mechanism of VPA-induced developmental toxicity and propose NRF2 activation as a means to preserve proper neurogenesis.

Measuring depression and anxiety in autistic college students: A psychometric evaluation of the PHQ-9 and GAD-7.

LAY ABSTRACT: Anxiety, depression, and suicidality are major concerns among college students, though less is known about these constructs in autistic college students. Given the rising number of autistic individuals entering college, adequate screening and diagnosis of mental health difficulties is necessary to provide care to this population. For example, despite widespread usage of the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), it is unknown if the two instruments accurately measure depression and anxiety the same way between non-autistic and autistic individuals. Thus, the current study was the first to examine how these instruments measure depression and anxiety symptoms in autistic versus non-autistic college students. Utilizing tests of construct measurement in a sample of autistic (n = 477) and non-autistic (n = 429) university students aged 18-29, results showed that while the GAD-7 and PHQ-9 appear to be accurately capturing anxiety and depression in autistic college students, the PHQ-9 item assessing suicidality was found to be measuring different things. This indicates that autistic college students are not interpreting this question the way non-autistic students are, and thus, the measure is failing to capture suicidality in autistic people. Future investigators should continue to assess the appropriateness of using common screening measures, originally created by non-autistic people, in autistic populations.

The Multisystem effects of Long COVID Syndrome and Potential Benefits of Massage Therapy in Long COVID Care.

Background: A major complication of infection with Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, is the potential for Long COVID Syndrome. While the pathophysiology of Long COVID Syndrome has yet to be described, the disease presentation is characterized by long-term symptoms with debilitating effects on human health. A better understanding of Long COVID symptomology may open up new avenues for patient treatment such as massage therapy. Methods: From the PubMed database, cohort studies that examined post-infection COVID sequelae published between January 1st, 2021 and April 30th, 2021 were selected to investigate patient demographics and symptoms. A review of massage therapy literature since 2000 in conjunction with identified Long COVID symptoms was performed. Results: This systematic review identified 17 cohort studies across the world that investigated the symptomatology of patients suffering from post-COVID sequelae in multiple organ systems. We identified the pulmonary and nervous systems to be the organ systems most affected with post-COVID sequelae, with PTSD, fatigue, dyspnea, cough, sleep disturbances, loss of smell, abdominal pain, and decreased appetite as the most common symptoms reported by >20% of Long COVID patients. Massage therapy was historically found to provide benefits to patients experiencing similar symptoms to those identified in Long COVID. Conclusions: Recognizing the need for new approaches to treatment for Long COVID Syndrome, we identify massage therapy as a potential therapeutic treatment to positively impact the organ systems affected by Long COVID, especially the high-incident symptoms, and improve patient quality of life.

Metabolic and Perceptual Responses to Constant Heart Rate Exercise at Vigorous Intensities in Women.

PURPOSE: This study quantified the metabolic demands (oxygen uptake (V̇O 2 )), power output adjustments, changes in the V̇O 2 /power output ratio, and perceptual responses (rating of perceived exertion (RPE)) during constant heart rate (HR) exercise performed within the vigorous intensity range (77%-95% HR peak ). METHODS: Twelve women (mean ± SD age, 22 ± 4 yr) performed a graded exercise test to exhaustion to determine peak parameters, and three randomly ordered, constant HR trials to exhaustion or for 60 min at the lower (HR L = 77% HR peak ), middle (HR M = 86% HR peak ), and higher (HR H = 95% HR peak ) end of the vigorous intensity range. Time course of changes and patterns of responses were examined for V̇O 2 , power output, V̇O 2 /power output, and RPE for the composite and for each subject. RESULTS: Across the HR L (time to exhaustion ( Tlim ) = 56.3 ± 9.9 min), HR M (51.8 ± 13.5 min), and HR H (27.2 ± 17.7 min) trials, V̇O 2 and power output decreased quadratically ( P < 0.05) relative to the initial value from 10% to 100% of Tlim , whereas the V̇O 2 /power output increased quadratically from 20% to 100% Tlim , and RPE increased linearly from 50% to 100% Tlim . The V̇O 2 and RPE, collapsed across time, for HR L (54.3% ± 3.3% V̇O 2peak , 11 ± 1.5 RPE) were lower than HR M (64.9% ± 4.5% V̇O 2peak , 14 ± 1.7 RPE), and both were lower than HR H (80.1% ± 4.1% V̇O 2peak , 17 ± 1.4 RPE). None of the 12 subjects at HR L , 6 at HR M , and 7 at HR H were within the vigorous V̇O 2 range. CONCLUSIONS: The HR L was not sufficient to meet the desired metabolic intensity for vigorous exercise, whereas the middle to higher end of the range elicited a V̇O 2 within the prescribed range of only ~50%-60% of the subjects. This study indicated that exercise held constant at a percentage of HR peak cannot consistently be used to prescribe a desired metabolic stimulus.

Blood flow restriction increases necessary muscle excitation of the elbow flexors during a single high-load contraction.

PURPOSE: To investigate the effects of blood flow restriction (BFR) on electromyographic amplitude (EMGRMS)-force relationships of the biceps brachii (BB) during a single high-load muscle action. METHODS: Twelve recreationally active males and eleven recreationally active females performed maximal voluntary contractions (MVCs), followed by an isometric trapezoidal muscle action of the elbow flexors at 70% MVC. Surface EMG was recorded from the BB during BFR and control (CON) visits. For BFR, cuff pressure was 60% of the pressure required to completely occlude blood at rest. Individual b (slope) and a terms (gain) were calculated from the log-transformed EMGRMS-force relationships during the linearly increasing and decreasing segments of the trapezoid. EMGRMS during the steady force segment was normalized to MVC EMGRMS. RESULTS: For BFR, the b terms were greater during the linearly increasing segment than the linearly decreasing segment (p < 0.001), and compared to the linearly increasing segment for CON (p < 0.001). The a terms for BFR were greater during the linearly decreasing than linearly increasing segment (p = 0.028). Steady force N-EMGRMS was greater for BFR than CON collapsed across sex (p = 0.041). CONCLUSION: BFR likely elicited additional recruitment of higher threshold motor units during the linearly increasing- and steady force-segment. The differences between activation and deactivation strategies were only observed with BFR, such as the b terms decreased and the a terms increased for the linearly decreasing segment in comparison to the increasing segment. However, EMGRMS-force relationships during the linearly increasing- and decreasing-segments were not different between sexes during BFR and CON.

Functional diversification of gram-negative intermembrane phospholipid transporters by intrinsic substrate preference.

The outer membrane of Gram-negative bacteria is a barrier to chemical and physical stress. Phospholipid transport between the inner and outer membranes has been an area of intense investigation and, in E. coli K-12, it has recently been shown to be mediated by YhdP, TamB, and YdbH, which are suggested to provide hydrophobic channels for phospholipid diffusion, with YhdP and TamB playing the major roles. However, YhdP and TamB have different phenotypes suggesting distinct functions. We investigated these functions using synthetic cold sensitivity (at 30 °C) of a strain with deletion of yhdP, but not tamB or ydbH, and fadR, a transcriptional regulator controlling fatty acid degradation and unsaturated fatty acid production. Deletion of tamB, redirecting phospholipid transport to YdbH, suppresses the ΔyhdP ΔfadR cold sensitivity suggesting this phenotype is directly related to phospholipid transport. The ΔyhdP ΔfadR strain shows a greater increase in cardiolipin upon transfer to the non-permissive temperature and genetically lowering cardiolipin levels can suppress cold sensitivity. These data also reveal a qualitative difference between cardiolipin synthases in E. coli, as deletion of clsA and clsC suppresses cold sensitivity but deletion of clsB does not despite lower cardiolipin levels. In addition to increased cardiolipin, increased fatty acid saturation is necessary for cold sensitivity and lowering this level genetically or through supplementation of oleic acid suppresses the cold sensitivity of the ΔyhdP ΔfadR strain. A parsimonious explanation for our data is that YhdP and TamB have differential substrate transport preferences, most likely with YhdP preferentially transporting more saturated phospholipids and TamB preferentially transporting more unsaturated phospholipids. We envision cardiolipin contributing to this transport preference by sterically clogging TamB-mediated transport of saturated phospholipids. Thus, our data provide a potential mechanism for independent control of the phospholipid composition of the inner and outer membranes in response to changing conditions.

Do anxiety symptoms and coping motives serially mediate the association between psychotic-like experiences and cannabis-related problems in undergraduate recent cannabis users?

Many Canadian emerging adults (ages 18-25 years) use cannabis, with 60 % of past-three-month users experiencing one or more cannabis-related problems (i.e., adverse consequences of use). While psychotic-like experiences (PLEs) and cannabis problems overlap, little is known about the mechanisms explaining this link. One hypothesis is that PLEs are distressing and give rise to anxiety, with which emerging adults attempt to cope through increased cannabis use, in turn increasing their risk for cannabis-related problems. We tested a chained-mediational model to determine if anxiety and coping-with-anxiety motives for cannabis use sequentially mediated the link between PLEs and cannabis problems in emerging adult undergraduates; a conditional process model tested for moderation by sex. Emerging adult cannabis users (N = 413; mean [SD] age = 19.1 [1.5] years; 71.9 % female) from five Canadian universities provided cross-sectional, self-report survey data in fall 2021. Validated measures of PLEs, anxiety, cannabis coping-with-anxiety motives, and cannabis-related problems were administered. Path analyses supported the hypothesized chained mediational indirect effect (b = 0.027, 95 % bootstrap CI [0.012, 0.050]). No direct effect was found (p =.698), suggesting that the PLEs-to-cannabis problems association is fully explained by anxiety and cannabis coping-with-anxiety motives. Inconsistent with hypotheses, mediation did not depend on sex (95 % CIs crossed zero); therefore, anxiety and cannabis coping-with-anxiety motives explain the link between PLEs and cannabis problems in emerging adults regardless of their sex. Results highlight anxiety and cannabis coping-with-anxiety motives as potentially important intervention targets in cannabis-using emerging adults with PLEs, possibly preventing the development/worsening of cannabis-related problems.

Evaluation of Work Efficiency in Structural Firefighters.

ABSTRACT: Langford, EL, Bergstrom, HC, Lanham, S, Eastman, AQ, Best, S, Ma, X, Mason, MR, and Abel, MG. Evaluation of work efficiency in structural firefighters. J Strength Cond Res 37(12): 2457-2466, 2023-To perform occupational tasks safely and effectively, firefighters (FF) must work quickly and consume air provided by the self-contained breathing apparatus (SCBA) efficiently. However, most literature only factors work rate into performance, neglecting the inherent time limitation imposed by the SCBA. The purpose of this article was to (a) evaluate the reliability and variability in a "work efficiency" (WE) performance metric reflective of both work rate and air consumption; (b) explore the relationship between WE and established measures of metabolic strain; and (c) identify fitness, anthropometric, and demographic correlates of WE. About 79 structural FF completed an air consumption drill while breathing through an SCBA. Self-paced work duration and air consumption were entered into the WE equation. A subsample of FF (n = 44) completed another randomized trial while breathing through a portable gas analyzer. Anthropometric and fitness data were collected separately. Correlations were performed between WE vs. fitness, anthropometric, demographic, and metabolic outcomes. Multiple linear regression was used to identify the strongest predictors of WE. WE was reliable (intraclass correlation coefficient = 0.71) and yielded inter-FF variability {0.79 ± 0.25 ([lb·in-2·min]-1) × 104; coefficient of variation = 31.6%}. WE was positively correlated to oxygen consumption (V̇O2) (L·minute-1, mL·kg-1·minute-1) and tidal volume and negatively correlated to V̇E/V̇O2 and respiratory frequency. Height, upper-body endurance, and aerobic endurance were identified as the strongest predictors of WE (adjusted R2 = 0.59, RMSE = 0.16). WE is a reliable and occupationally relevant method to assess FF performance because it accounts for work rate and air consumption. Firefighters may enhance WE through a training intervention focused on improving metabolic tolerance, upper-body endurance, and aerobic endurance.

Prevention of Alzheimer Pathology by Blocking Neuregulin Signaling on Microglia.

Plaque formation, microglial activation, and synaptic loss are pathologic hallmarks of Alzheimer's disease; however, removing plaques has had little clinical benefit. Here, we show that neuregulin-1, a glial growth factor, induces inflammatory cytokines and promotes phagocytic activity in vitro and augments microglial activation and plaque formation in 5XFAD Alzheimer's mice. Brain-specific targeting of neuregulin-1 by intraventricular delivery of a novel neuregulin-1 fusion protein antagonist, GlyB4, significantly alters microglial morphology and function to a nonpathogenic morphology in early-stage 5XFAD mice and prevents plaques from forming. Once plaques have already formed, GlyB4 reduces new plaque formation and prevents synaptic loss. Selective, targeted disruption of neuregulin-1 signaling on brain microglia with GlyB4 could be a novel "upstream" approach to slow or stop disease progression in Alzheimer's disease.

Analysis of Individual V˙O2max Responses during a Cardiopulmonary Exercise Test and the Verification Phase in Physically Active Women.

This study aimed to investigate the test-retest reliability, mean, and individual responses in the measurement of maximal oxygen consumption (V˙O2max) during a cardiopulmonary exercise test (CPET) and the verification phase during cycle ergometry in women. Nine women (22 ± 2 yrs, 166.0 ± 4.5 cm, 58.6 ± 7.7 kg) completed a CPET, passively rested for 5 min, and then completed a verification phase at 90% of peak power output to determine the highest V˙O2 from the CPET (V˙O2CPET) and verification phase (V˙O2verification) on 2 separate days. Analyses included a two-way repeated measures ANOVA, intraclass correlation coefficients (ICC2,1), standard errors of the measurement (SEM), minimal differences (MD), and coefficients of variation (CoV). There was no test (test 1 versus test 2) × method (CPET vs. verification phase) interaction (p = 0.896) and no main effect for method (p = 0.459). However, test 1 (39.2 mL·kg-1·min-1) was significantly higher than test 2 (38.3 mL·kg-1·min-1) (p = 0.043). The V˙O2CPET (ICC = 0.984; CoV = 1.98%; SEM = 0.77 mL·kg-1·min-1; MD = 2.14 mL·kg-1·min-1) and V˙O2verification (ICC = 0.964; CoV = 3.30%; SEM = 1.27 mL·kg-1·min-1; MD = 3.52 mL·kg-1·min-1) demonstrated "excellent" reliability. Two subjects demonstrated a test 1 V˙O2CPET that exceeded the test 2 V˙O2CPET, and one subject demonstrated a test 1 V˙O2verification that exceeded the test 2 V˙O2verification by more than the respective CPET and verification phase MD. One subject demonstrated a V˙O2CPET that exceeded the V˙O2verification, and one subject demonstrated a V˙O2verification that exceeded the V˙O2CPET by more than the MD. These results demonstrate the importance of examining the individual responses in the measurement of the V˙O2max and suggest that the MD may be a useful threshold to quantify real individual changes in V˙O2.

Bouncing Back: Resilience as a Protective Factor for the Impact of Child Problem Behavior on Caregiver Depressive Cognitions Among Youth with Autism Spectrum Disorder.

Caregivers of children with autism spectrum disorder (ASD) often report higher rates of depression and the related negative thought patterns that may precede a clinical diagnosis. These negative thought patterns are referred to as depressive cognitions. Depressive cognitions are exacerbated by child problem behaviors (CPB) but may be impacted by parental resilience. The current study examines relations between CPB and depressive cognitions and the role of resilience as a moderator among caregivers of children with ASD (n = 287) and a sample of caregivers of children who are typically developing (n = 207). Significant positive associations were found between CPB and depressive cognitions for caregivers of children with ASD and who are typically developing. A moderation analysis revealed that, among the ASD sample, the model accounted for 33% of the variance in caregiver depressive cognitions (R2 = 0.33, SE = 35.52, p < 0.001). The interaction of child problem behaviors and caregiver resilience on caregiver depressive cognitions was statistically significant (B = - 0.016, SE = 0.007, p = 0.037), thus resilience was a significant moderator, for caregivers of children with ASD. Resilience serves as a protective factor in the relationship between child problem behavior and caregiver depressive cognitions for caregivers of children with ASD only. This finding highlights the importance of assessing and supporting resilience among caregivers of children with ASD. Interventions addressing child behavior would benefit from additional components to bolster caregiver resilience to enhance caregiver mental health and protect against depressive cognitions.

Combinatorial fedratinib and venetoclax treatment is effective on human B cell acute lymphoblastic leukemia with high Flt3 expression.

Treatment of relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) remains a challenge, particularly in patients who do not respond to traditional chemotherapy or immunotherapy. The objective of this study was to assess the efficacy of fedratinib, a semi selective JAK2 inhibitor and venetoclax, a selective BCL-2 inhibitor, on human B-ALL using both single-agent and combinatorial treatments. The combination treatment of fedratinib and venetoclax improved killing of the human B-ALL cell lines RS4;11 and SUPB-15 in vitro over single-agent treatments. This combinatorial effect was not detected in the human B-ALL cell line NALM-6, which was less responsive to fedratinib due to the absence of Flt3 expression. The combination treatment induces a unique gene expression profile relative to single-agent treatment and with an enrichment in apoptotic pathways. Finally, the combination treatment was superior to single agent treatment in an in vivo xenograft model of human B-ALL with a two-week treatment regimen significantly improving overall survival. Overall, our data demonstrates the efficacy of a combinatorial treatment strategy of fedratinib and venetoclax against human B-ALL expressing high levels of Flt3.