Retinal hyperspectral imaging in mouse models of Parkinson's disease and healthy aging.

Retinal hyperspectral imaging (HSI) is a non-invasive in vivo approach that has shown promise in Alzheimer's disease. Parkinson's disease is another neurodegenerative disease where brain pathobiology such as alpha-synuclein and iron overaccumulation have been implicated in the retina. However, it remains unknown whether HSI is altered in in vivo models of Parkinson's disease, whether it differs from healthy aging, and the mechanisms which drive these changes. To address this, we conducted HSI in two mouse models of Parkinson's disease across different ages; an alpha-synuclein overaccumulation model (hA53T transgenic line M83, A53T) and an iron deposition model (Tau knock out, TauKO). In comparison to wild-type littermates the A53T and TauKO mice both demonstrated increased reflectivity at short wavelengths ~ 450 to 600 nm. In contrast, healthy aging in three background strains exhibited the opposite effect, a decreased reflectance in the short wavelength spectrum. We also demonstrate that the Parkinson's hyperspectral signature is similar to that from an Alzheimer's disease model, 5xFAD mice. Multivariate analyses of HSI were significant when plotted against age. Moreover, when alpha-synuclein, iron or retinal nerve fibre layer thickness were added as a cofactor this improved the R2 values of the correlations in certain groups. This study demonstrates an in vivo hyperspectral signature in Parkinson's disease that is consistent in two mouse models and is distinct from healthy aging. There is also a suggestion that factors including retinal deposition of alpha-synuclein and iron may play a role in driving the Parkinson's disease hyperspectral profile and retinal nerve fibre layer thickness in advanced aging. These findings suggest that HSI may be a promising translation tool in Parkinson's disease.

Is there evidence for the asymmetrical transfer of strength to an untrained limb?

PURPOSE: The literature predominantly addresses cross-education of strength in the dominant limb rather than the non-dominant limb, guided by the hypothesis of an asymmetrical transfer of strength from unilateral training protocols. The purpose of the study was to review the literature and determine how much evidence was available to support this claim. A meta-analysis was performed to estimate the magnitude of this hypothesized asymmetrical transfer of strength. METHODS: A literature search of all possible records was implemented using Cochrane Library, PubMed, and Scopus from February 2022 to May 2022. Comparison of randomized controlled trials was computed. The change scores and standard deviations of those change scores were extracted for each group. Only three studies met the criteria, from which a total of five effect sizes were extracted and further analyzed. RESULTS: The overall effect of resistance training of the dominant limb on strength transfer to the non-dominant limb relative to the effects of resistance training the non-dominant limb on strength transfer to the dominant (non-training) limb was 0.46 (SE 0.42). The analysis from this study resulted in minimal support for the asymmetry hypothesis. Given the small number of studies available, we provide the effect but note that the estimate is unlikely to be stable. CONCLUSION: Although it is repeatedly stated that there is an asymmetrical transfer of strength, our results find little support for that claim. This is not to say that it does not exist, but additional research implementing a control group and a direct comparison between limbs is needed to better understand this question.

Blood flow restriction pressure for narrow cuffs (5 cm) cannot be estimated with precision.

Blood flow restriction pressures are set relative to the lowest pressure needed to occlude blood flow with that specific cuff. Due to pressure limitations of some devices, it is often not possible to occlude blood flow in all subjects and apply a known relative pressure in the lower body with a 5 cm wide cuff.Objective. To use a device capable of generating high pressures (up to 907 mmHg) to create and validate an estimation equation for the 5 cm cuff in the lower body using a 12 cm cuff.Approach. 170 participants had their arterial occlusion pressure (AOP) with a 5 cm and 12 cm cuff and their thigh circumference measured in their right leg. The sample was randomly allocated to a prediction group (66%) and validation group (33%). Thigh circumference and 12 cm AOP were used as predictors. A Bland-Altman plot was constructed to assess agreement between measured and predicted values.Main results. The mean difference (95% confidence interval) between the observed (336.8 mmHg) and the predicted (343.9 mmHg) 5 cm AOP was 7.1 (-11.9, 26.1) mmHg. The 95% limits of agreement were -133.6 to 147.8 mmHg. There was a negative relationship between the difference and the average of predicted and measured 5 cm AOP (B= -0.317,p= 0.000043).Significance. Although this was the first study to quantify AOP over 600 mmHg with a 5 cm cuff, our equation is not valid across all levels of pressure. If possible, larger cuff widths should be employed in the lower body.

Blood flow restriction augments exercise-induced pressure pain thresholds over repetition and effort matched conditions.

We sought to determine the effects of blood flow restriction (BFR) on exercise-induced hypoalgesia, specifically using low-load (LL) resistance exercise (30% 1RM) protocols that accounted for each individual's local muscular endurance capabilities. Forty-four participants completed four conditions: (1) 70% of maximal BFR repetitions with blood flow restriction (LL+BFR exercise); (2) 70% maximal BFR repetitions without LL+BFR (LL exercise); (3) 70% maximal free flow repetitions (LL+EFFORT exercise); (4) time-matched, non-exercise control (CON). Pressure pain threshold (PPT) was measured before and after exercise. Ischaemic pain threshold and tolerance was assessed only at post. The change in upper body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.15 (0.35) kg/cm2], LL+EFFORT exercise [difference of 0.23 (0.45) kg/cm2], and the CON condition. The change in lower body PPT was greater for LL+BFR exercise compared to LL exercise [difference of 0.40 (0.55) kg/cm2], LL+EFFORT exercise [difference of 0.36 (0.62) kg/cm2], and the CON condition. Ischaemic pain thresholds and tolerances did not change. Submaximal exercise with BFR resulted in systemic increases in PPT but had no influence on ischaemic pain sensitivity. This effect is likely unique to BFR as we did not see changes in the effort matched free flow condition.

Blood flow restriction augments the cross-education effect of isometric handgrip training.

INTRODUCTION: The application of blood flow restriction (BFR) to low-intensity exercise may be able to increase strength not only in the trained limb but also in the homologous untrained limb. Whether this effect is repeatable and how that change compares to that observed with higher intensity exercise is unknown. PURPOSE: Examine whether low-intensity training with BFR enhances the cross-education of strength compared to exercise without BFR and maximal efforts. METHODS: A total of 179 participants completed the 6-week study, with 135 individuals performing isometric handgrip training over 18 sessions. Participants were randomly assigned to one of four groups: 1) low-intensity (4 × 2 min of 30% MVC; LI, n = 47), 2) low-intensity with blood flow restriction (LI + 50% arterial occlusion pressure; LI-BFR, n = 41), 3) maximal effort (4 × 5 s of 100% MVC; MAX, n = 47), and 4) non-exercise control (CON, n = 44). RESULTS: LI-BFR was the only group that observed a cross-education in strength (CON: 0.64 SD 2.9 kg, LI: 0.95 SD 3.6 kg, BFR-LI: 2.7 SD 3.3 kg, MAX: 0.80 SD 3.1 kg). In the trained hand, MAX observed the greatest change in strength (4.8 SD 3.3 kg) followed by LI-BFR (2.8 SD 4.0 kg). LI was not different from CON. Muscle thickness did not change in the untrained arm, but ulna muscle thickness was increased within the trained arm of the LI-BFR group (0.06 SD 0.11 cm). CONCLUSION: Incorporating BFR into low-intensity isometric training led to a cross-education effect on strength that was greater than all other groups (including high-intensity training).

Levodopa Rescues Retinal Function in the Transgenic A53T Alpha-Synuclein Model of Parkinson's Disease.

BACKGROUND: Loss of substantia nigra dopaminergic cells and alpha-synuclein (α-syn)-rich intraneuronal deposits within the central nervous system are key hallmarks of Parkinson's disease (PD). Levodopa (L-DOPA) is the current gold-standard treatment for PD. This study aimed to evaluate in vivo retinal changes in a transgenic PD model of α-syn overexpression and the effect of acute levodopa (L-DOPA) treatment. METHODS: Anaesthetised 6-month-old mice expressing human A53T alpha-synuclein (HOM) and wildtype (WT) control littermates were intraperitoneally given 20 mg/kg L-DOPA (50 mg levodopa, 2.5 mg benserazide) or vehicle saline (n = 11-18 per group). In vivo retinal function (dark-adapted full-field ERG) and structure (optical coherence tomography, OCT) were recorded before and after drug treatment for 30 min. Ex vivo immunohistochemistry (IHC) on flat-mounted retina was conducted to assess tyrosine hydroxylase (TH) positive cell counts (n = 7-8 per group). RESULTS: We found that photoreceptor (a-wave) and bipolar cell (b-wave) ERG responses (p < 0.01) in A53T HOM mice treated with L-DOPA grew in amplitude more (47 ± 9%) than WT mice (16 ± 9%) treated with L-DOPA, which was similar to the vehicle group (A53T HOM 25 ± 9%; WT 19 ± 7%). While outer retinal thinning (outer nuclear layer, ONL, and outer plexiform layer, OPL) was confirmed in A53T HOM mice (p < 0.01), L-DOPA did not have an ameliorative effect on retinal layer thickness. These findings were observed in the absence of changes to the number of TH-positive amacrine cells across experiment groups. Acute L-DOPA treatment transiently improves visual dysfunction caused by abnormal alpha-synuclein accumulation. CONCLUSIONS: These findings deepen our understanding of dopamine and alpha-synuclein interactions in the retina and provide a high-throughput preclinical framework, primed for translation, through which novel therapeutic compounds can be objectively screened and assessed for fast-tracking PD drug discovery.

The Impact of Different Ischemic Preconditioning Pressures on Pain Sensitivity and Resistance Exercise Performance.

ABSTRACT: Kataoka, R, Song, JS, Yamada, Y, Hammert, WB, Seffrin, A, Spitz, RW, Wong, V, Kang, A, and Loenneke, JP. The impact of different ischemic preconditioning pressures on pain sensitivity and resistance exercise performance. J Strength Cond Res 38(5): 864-872, 2024-To determine (a) the impact of ischemic preconditioning pressures (applied as a % of arterial occlusion pressure [AOP]) on pressure pain threshold (PPT) and resistance exercise performance and (b) whether changes in performance could be explained by changes in PPT. Subjects ( n = 39) completed 4 protocols in a randomized order: (a) ischemic preconditioning (IPC) at 110% AOP (IPC 110%), (b) IPC at 150% AOP (IPC 150%), (c) IPC at 10% AOP (Sham), and (d) time-matched control (CON). Each protocol included 4 cycles of 5 minutes of occlusion followed by 5 minutes of reperfusion. Pressure pain threshold was taken before and after. Discomfort ratings were given at the end of each cycle. Every visit finished with 2 sets of 75-second maximal isokinetic unilateral elbow flexion or extension. Overall, IPC 110% and IPC 150% resulted in similar increases in PPT relative to CON [110%: difference of 0.36 (0.18, 0.54) kg·m -2 ; 150%: difference of 0.377 (0.15, 0.59) kg·m -2 ] and Sham. Both resulted in greater discomfort than Sham and CON, with IPC 150% inducing greater discomfort than IPC 110% (BF 10 : 14.74). There were no differences between the conditions for total work (BF 10 : 0.23), peak torque (BF 10 : 0.035), or average power (BF 10 : 0.159). We did not find evidence that PPT mediated performance. We did not detect changes in performance with 2 different relative pressures greater than AOP. Our mean applied pressures were lower than those used previously. There might be a minimal level of pressure (e.g., >150% of AOP) that is required to induce ergogenic effects of ischemic preconditioning.

The Plateau in Muscle Growth with Resistance Training: An Exploration of Possible Mechanisms.

It is hypothesized that there is likely a finite ability for muscular adaptation. While it is difficult to distinguish between a true plateau following a long-term training period and short-term stalling in muscle growth, a plateau in muscle growth has been attributed to reaching a genetic potential, with limited discussion on what might physiologically contribute to this muscle growth plateau. The present paper explores potential physiological factors that may drive the decline in muscle growth after prolonged resistance training. Overall, with chronic training, the anabolic signaling pathways may become more refractory to loading. While measures of anabolic markers may have some predictive capabilities regarding muscle growth adaptation, they do not always demonstrate a clear connection. Catabolic processes may also constrain the ability to achieve further muscle growth, which is influenced by energy balance. Although speculative, muscle cells may also possess cell scaling mechanisms that sense and regulate their own size, along with molecular brakes that hinder growth rate over time. When considering muscle growth over the lifespan, there comes a point when the anabolic response is attenuated by aging, regardless of whether or not individuals approach their muscle growth potential. Our goal is that the current review opens avenues for future experimental studies to further elucidate potential mechanisms to explain why muscle growth may plateau.

Can we improve exercise-induced hypoalgesia with exercise training? An overview and suggestions for future studies.

Exercise-induced hypoalgesia refers to a reduction in pain sensitivity following a single bout of exercise, which has been shown to be diminished or impaired with aging and chronic pain. Exercise training (repeated bouts of exercise over time) is often recommended as a non-pharmacological treatment for chronic pain and age-related functional declines. However, whether exercise training can augment the exercise-induced hypoalgesia has not been well studied. The purpose of this paper is to 1) provide an overview of the existing literature investigating the effect of exercise training on the magnitude of exercise-induced hypoalgesia, and 2) discuss potential underlying mechanisms as well as considerations for future research. Given the paucity of randomized controlled trials in this area, the effects of exercise training on exercise-induced hypoalgesia are still unclear. Several potential mechanisms have been proposed to explain the impaired exercise-induced hypoalgesia in chronic pain and older individuals (e.g., endogenous opioid, cardiovascular, and immune system). Exercise training appears to induce physiological changes in those systems, however, further investigations are necessary to test whether this will lead to improved exercise-induced hypoalgesia. Future research should consider including a time- and age-matched non-training group and utilizing the same exercise protocol for testing exercise-induced hypoalgesia across intervention groups.

Measuring the Full-Field Electroretinogram in Rodents.

Electroretinography allows for noninvasive functional assessment of the retina and is a mainstay for preclinical studies of retinal function in health and disease. The full-field electroretinogram is useful for a variety of applications as it returns a functional readout from each of the major cell classes within the retina: photoreceptors, bipolar cells, amacrine cells, and retinal ganglion cells. Rodent models are commonly employed in ocular degeneration studies due to the fast throughput of these mammalian species and the conservation of the electroretinogram from the preclinic to the clinic. Here we describe approaches for in vivo electroretinography in rodent models.

Age-related deficits in retinal autophagy following intraocular pressure elevation in autophagy reporter mouse model.

This study quantified age-related changes to retinal autophagy using the CAG-RFP-EGFP-LC3 autophagy reporter mice and considered how aging impacts autophagic responses to acute intraocular pressure (IOP) stress. IOP was elevated to 50 mm Hg for 30 minutes in 3-month-old and 12-month-old CAG-RFP-EGFP-LC3 (n = 7 per age group) and Thy1-YFPh transgenic mice (n = 3 per age group). Compared with younger eyes, older eyes showed diminished basal autophagy in the outer retina, while the inner retina was unaffected. Autophagic flux (red:yellow puncta ratio) was elevated in the inner plexiform layer. Three days following IOP elevation, older eyes showed poorer functional recovery, most notably in ganglion cell responses compared to younger eyes (12 months old: -33.4 ±â€¯5.3% vs. 3 months mice: -13.4 ±â€¯4.5%). This paralleled a reduced capacity to upregulate autophagic puncta volume in the inner retina in older eyes, a response that was seen in younger eyes. Age-related decline in basal and stress-induced autophagy in the retina is associated with greater retinal ganglion cells' susceptibility to IOP elevation.

Unilateral high-load resistance training influences strength changes in the contralateral arm undergoing low-load training.

OBJECTIVES: Within-subject training models have become common within the exercise literature. However, it is currently unknown if training one arm with a high load would impact muscle size and strength of the opposing arm training with a low load. DESIGN: Parallel group. METHODS: 116 participants were randomized to one of three groups that completed 6-weeks (18 sessions) of elbow flexion exercise. Group 1 trained their dominant arm only, beginning with a one-repetition maximum test (≤5 attempts), followed by four sets of exercise using a weight equivalent to 8-12 repetition maximum. Group 2 completed the same training as Group 1 in their dominant arm, while the non-dominant arm completed four sets of low-load exercise (30-40 repetition maximum). Group 3 trained their non-dominant arm only, performing the same low-load exercise as Group 2. Participants were compared for changes in muscle thickness and elbow flexion one-repetition maximum. RESULTS: The greatest changes in non-dominant strength were present in Groups 1 (Δ 1.5 kg; untrained arm) and 2 (Δ1.1 kg; low-load arm with high load on opposite arm), compared to Group 3 (Δ 0.3 kg; low-load only). Only the arms being directly trained observed changes in muscle thickness (≈Δ 0.25 cm depending on site). CONCLUSIONS: Within-subject training models are potentially problematic when investigating changes in strength (though not muscle growth). This is based on the finding that the untrained limb of Group 1 saw similar changes in strength as the non-dominant limb of Group 2 which were both greater than the low-load training limb of Group 3.

Improved interference control after exercise with blood flow restriction and cooling is associated with but not mediated by increased lactate.

BACKGROUND: To evaluate the effects of recumbent sprint interval exercise with and without blood flow restriction and body cooling on interference control and whether the changes in interference control can be explained by the changes in blood lactate. METHODS: 85 participants (22 SD 3 years old) completed 1 familiarization visit and then 5 experimental visits in a randomized order: exercise only (Ex), exercise with blood flow restriction (ExB), exercise with cooling (ExC), and exercise with blood flow restriction and cooling (ExBC), and non-exercise control (Con). Measurements of blood lactate and the Stroop Color Word Test were performed before and after exercise. Each bout began with a 15-minute low-moderate intensity warm-up, followed by five 20-second "all out" sprints separated by 40 s of active recovery. Bayes Factors (BF10) quantified evidence for or against the null hypothesis. Within-subject mediation analysis quantified the indirect effect of changes in blood lactate (mediator) on the change in interference control (each exercise condition vs. Con). RESULTS: Bayesian pairwise comparisons found that only ExC [σ: -0.37 (-0.59, -0.15)] and ExBC [σ: -0.3 (-0.53, -0.09)] produced changes in incongruent reaction time different from that of Con. There was also evidence that all exercise conditions increased blood lactate (BF10 = 8.65e+29 - 1.9e+32) and improved congruent reaction time (BF10 = 4.01 - 15.371) compared to that of Con. There was no evidence to show that changes in lactate mediated the change in incongruent reaction time. CONCLUSIONS: Both exercise with body cooling and when body cooling was combined with blood flow restriction presented favorable changes in incongruent reaction time (a marker of interference control), which might not be explained by the changes in systemic blood lactate concentration.

Retinal Assessment Using In Vivo Electroretinography and Optical Coherence Tomography in Rodent Models of Diabetes.

Electroretinography and optical coherence tomography imaging allow for non-invasive quantitative assessment of the retina. These approaches have become mainstays for identifying the very earliest impact of hyperglycemia on retinal function and structure in animal models of diabetic eye disease. Moreover, they are essential for assessing the safety and efficacy of novel treatment approaches for diabetic retinopathy. Here, we describe approaches for in vivo electroretinography and optical coherence tomography imaging in rodent models of diabetes.

Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson's disease.

Abnormal alpha-synuclein (α-SYN) protein deposition has long been recognized as one of the pathological hallmarks of Parkinson's disease's (PD). This study considers the potential utility of PD retinal biomarkers by investigating retinal changes in a well characterized PD model of α-SYN overexpression and how these correspond to the presence of retinal α-SYN. Transgenic A53T homozygous (HOM) mice overexpressing human α-SYN and wildtype (WT) control littermates were assessed at 4, 6, and 14 months of age (male and female, n = 15-29 per group). In vivo retinal function (electroretinography, ERG) and structure (optical coherence tomography, OCT) were recorded, and retinal immunohistochemistry and western blot assays were performed to examine retinal α-SYN and tyrosine hydroxylase. Compared to WT controls, A53T mice exhibited reduced light-adapted (cone photoreceptor and bipolar cell amplitude, p < 0.0001) ERG responses and outer retinal thinning (outer plexiform layer, outer nuclear layer, p < 0.0001) which correlated with elevated levels of α-SYN. These retinal signatures provide a high throughput means to study α-SYN induced neurodegeneration and may be useful in vivo endpoints for PD drug discovery.

Retinal Dysfunction in a Mouse Model of HCN1 Genetic Epilepsy.

Pathogenic variants in HCN1 are associated with a range of epilepsy syndromes including a developmental and epileptic encephalopathy. The recurrent de novo HCN1 pathogenic variant (M305L) results in a cation leak, allowing the flux of excitatory ions at potentials where the wild-type channels are closed. The Hcn1M294L mouse recapitulates patient seizure and behavioral phenotypes. As HCN1 channels are highly expressed in rod and cone photoreceptor inner segments, where they shape the light response, mutated channels are likely to impact visual function. Electroretinogram (ERG) recordings from male and female mice Hcn1M294L mice revealed a significant decrease in the photoreceptor sensitivity to light, as well as attenuated bipolar cell (P2) and retinal ganglion cell responses. Hcn1M294L mice also showed attenuated ERG responses to flickering lights. ERG abnormalities are consistent with the response recorded from a single female human subject. There was no impact of the variant on the structure or expression of the Hcn1 protein in the retina. In silico modeling of photoreceptors revealed that the mutated HCN1 channel dramatically reduced light-induced hyperpolarization, resulting in more Ca2+ flux during the response when compared with the wild-type situation. We propose that the light-induced change in glutamate release from photoreceptors during a stimulus will be diminished, significantly blunting the dynamic range of this response. Our data highlight the importance of HCN1 channels to retinal function and suggest that patients with HCN1 pathogenic variants are likely to have a dramatically reduced sensitivity to light and a limited ability to process temporal information.SIGNIFICANCE STATEMENT Pathogenic variants in HCN1 are emerging as an important cause of catastrophic epilepsy. HCN1 channels are ubiquitously expressed throughout the body, including the retina. Electroretinogram recordings from a mouse model of HCN1 genetic epilepsy showed a marked decrease in the photoreceptor sensitivity to light and a reduced ability to respond to high rates of light flicker. No morphologic deficits were noted. Simulation data suggest that the mutated HCN1 channel blunts light-induced hyperpolarization and consequently limits the dynamic range of this response. Our results provide insights into the role HCN1 channels play in retinal function as well as highlighting the need to consider retinal dysfunction in disease caused by HCN1 variants. The characteristic changes in the electroretinogram open the possibility of using this tool as a biomarker for this HCN1 epilepsy variant and to facilitate development of treatments.

Effect of Increased Pressure Pain Threshold on Resistance Exercise Performance With Blood Flow Restriction.

ABSTRACT: Kataoka, R, Song, JS, Bell, ZW, Wong, V, Spitz, RW, Yamada, Y, and Loenneke, JP. Effect of increased pressure pain threshold on resistance exercise performance with blood flow restriction. J Strength Cond Res 37(6): 1204-1210, 2023-This study aimed to examine whether increasing pressure pain threshold (PPT) through isometric handgrip exercise (HG) affects the number of repetitions completed and discomfort with knee extension exercise (KE) with blood flow restriction (BFR), and examine whether performing additional exercise leads to a further increase in PPT. Forty-one participants completed 2 trials: rest followed by low-load KE with BFR at 80% of resting arterial occlusion pressure (Rest + KE BFR) and low-intensity (30% of maximal strength) HG exercise followed by KE with BFR (HG + KE BFR). Pressure pain threshold was measured before and after exercise at the forearm and tibialis anterior. Results are presented as median difference (95% credible interval). Pressure pain threshold increased at the forearm (Bayes factor [BF 10 ]: 5.2 × 10 7 ) and tibialis anterior (BF 10 : 1.5 × 10 6 ) after HG exercise. However, this did not lead to greater repetitions being completed with BFR exercise (0.2 [-0.1, 0.6] repetitions, BF 10 : 0.07). Pressure pain threshold after BFR exercise was not augmented over that observed with HG exercise (0.02 [-0.15, 0.2] kg·cm -2 , BF 10 : 0.175) at the forearm. More data are needed in the lower body to determine which model best fits the data (BF 10 : 0.84). Discomfort with BFR exercise was not different between conditions (1.0 [-2.3, 4.4] arbitrary units, BF 10 : 0.10). The pain-reducing effect of prior exercise did not change the repetitions completed with BFR exercise, suggesting that the change in PPT may not have been great enough to alter performance. Performing additional exercise did not elicit further increases in PPT nor was perceived discomfort to BFR exercise altered by changes in PPT.

Does muscle growth mediate changes in a nonspecific strength task?

The purpose of this study was to determine if muscle growth mediates increases in a strength task which was not directly trained. One hundred fifty-one participants were randomized into control, one-repetition maximum training (1RM-TRAIN), or traditional training (TRAD-TRAIN). Training groups performed isotonic elbow flexion 3x/week for 6 weeks. Anterior muscle thickness at 50%, 60% and 70% upper arm length, and maximal isokinetic torque at 60°/sec were assessed pre- and post-training. Change-score mediation models (adjusted for sex, pre-muscle thickness, and pre-strength) were constructed for each muscle thickness site. The effects of each training group were evaluated relative to the control. Data is presented as coefficient (95% CI). There were no significant relative direct effects on nonspecific strength for either training group outside of the 60% model (1.7 [0.13, 3.27] Nm). The relative effect of 1RM-TRAIN on muscle thickness was greater in 60% (0.09 [0.01, 0.17] cm) and 70% (0.09 [0.00, 0.17] cm) models; while TRAD-TRAIN was greater in all three: (50% = 0.24 [0.15, 0.32]; 60% = 0.24 [0.16, 0.33]; 70% = 0.22 [0.14, 0.31] cm). The effect of muscle thickness on nonspecific strength was only significant for the 60% (-3.06 [-5.7, -0.35] Nm) model. The relative indirect effect on nonspecific strength was not significant for the 1RM-TRAIN or TRAD-TRAIN. Similar to previous findings on specific strength, we did not find evidence for a mediating effect of muscle growth on training induced increases in nonspecific strength. The importance of muscle growth for changes in nonspecifically trained strength may need to be reconsidered.

Sex segregation in strength sports: Do equal-sized muscles express the same levels of strength between sexes?

OBJECTIVES: Concerns have been raised against the current two-sex binary category in sports competitions. The thesis states that if males and females were separated based on muscle size, it would negate the strength advantage between the sexes. We tested the possible sex differences in various strength outcomes when pair-matched for muscle thickness. METHODS: A total of 16 different data sets (n = 963) were assessed to pair-match females with males who had a muscle thickness value within 2%. We further compared the competition performances of the smallest male weight class within the International Powerlifting Federation (IPF) to different weight classes in females. RESULTS: Overall, 76%-88% of the strength assessments were greater in males than females with pair-matched muscle thickness, regardless of contraction types (i.e., isotonic, isometric, isokinetic). Additionally, males in the lightest weight division in the IPF largely outperformed females in heavier weight divisions. CONCLUSIONS: Our results would suggest that segregation based on muscle mass or surrogates of muscle mass (e.g., lean body mass) might not be an appropriate classification to create fair competition within strength sports. This is not to refute the concept of the desegregation of the two-sex binary category but to present data that raises important concerns about the potential sex-based differences in strength performance.

Effect of hydroxychloroquine or chloroquine and short wavelength light on in vivo retinal function and structure in mouse eyes.

CLINICAL RELEVANCE: The use of chloroquine or hydroxychloroquine can lead to both acute and chronic changes to both retinal structure and function. BACKGROUND: Chloroquine (CQ) and hydroxychloroquine (HCQ) have the potential for retina toxicity. The acute impact of short-term drug exposure (2-4 weeks) on in vivo retinal structure and function and assess whether short wavelength light exposure further exacerbates any structural and functional changes was assessed in a murine model. METHODS: Adult C57BL/6 J mice received intraperitoneal injection of vehicle or hydroxychloroquine (10 mg/kg) 3 times per week for 2 or 4 weeks, or chloroquine for 4 weeks (10 mg/kg). Over this period, animals were exposed to room light (8 hours) or short-wavelength light 4 hours per day (4 hours of normal room light) for 5 days each week. Retinal changes were assessed using electroretinography (ERG), in vivo optical coherence tomography (OCT) imaging. RESULTS: Short-term low-dose HCQ and CQ treatment led to RPE thickening and elongation of photoreceptors. These structural changes were associated with a no dysfunction in the case of HCQ treatments and widespread functional changes (photoreceptor sensitivity, bipolar cell amplitude and oscillatory potential amplitude) in the case of CQ treatment. Exposure to low intensity short-wavelength light does not appear to alter the effect of HCQ or CQ. CONCLUSIONS: HCQ and CQ treatment has acute effects on both retinal structure and function, effects that were not exacerbated by short wavelength light exposure. Whether chronic short wavelength light exposure exacerbates these changes require further study.