Subjects increasing sperm DNA fragmentation (sDF) during Density Gradient Centrifugation (DGC), a common sperm selection procedure in Assisted Reproduction Techniques (ARTs), experience a 50% lower ...probability of pregnancy. Hence, identification of these subjects is of clinical importance. Here, we investigated whether such subjects are identified with higher accuracy detecting DNA fragmentation in viable (viable sDF) instead of total spermatozoa (total sDF) and whether swim up, an alternative procedure to DGC, does not increase sDF. With DGC, we identified 10/20 subjects increasing total sDF, and 2 more subjects using viable sDF. With swim up, we identified 8/40 subjects increasing total sDF, and 8 more subjects using viable sDF. In addition, viable sDF reveals more accurately the increase of the damage when it occurs. Finally, a multivariate analysis demonstrated that the proportional increase of sDF was higher after DGC respect to swim up. In conclusion, viable sDF is a more accurate parameter to reveal the increase of the damage by selection both with swim up and DGC. Swim up increases sDF in some samples, although at a lesser extent than DGC, suggesting that it should be used to select spermatozoa for ARTs when possible.
This paper provides a narrative review of cognitive motor interference in neurodegeneration, including brain imaging findings specific to interference effects in neurodegenerative disease, and dual ...task assessment and intervention in Parkinson's disease (PD), multiple sclerosis (MS), and Huntington's disease (HD). In a healthy central nervous system the ability to process information is limited. Limitations in capacity to select and attend to inputs influence the ability to prepare and perform multiple tasks. As a result, the system balances demands, switching attention to the most task-relevant information as it becomes available. Limitations may become more apparent in persons with neurodegenerative diseases (ND) with system-specific impairments in PD, MS, and HD. These ND affect both cognitive and motor function and are thus particularly susceptible to dual task interference. Issues related to performer and task characteristics and implications of these findings for both the standard assessment of dual task abilities as well as development and evaluation of interventions aimed at improving dual task ability are discussed. In addition, we address the need for optimizing individualized assessment, intervention and evaluation of dual task function by choosing cognitive and motor tasks and measures that are sensitive to and appropriate for the individual's level of function. Finally, we use current evidence to outline a 5-step process of clinical decision making that uses the dual task taxonomy as a framework for assessment and intervention.
Epidemiological studies reported a negative relationship between concentrations of heavy metals and phthalates in seminal fluid and semen quality, likely compromising male fertility potential. The ...aim of this study was to investigate the in vitro effects of cadmium chloride (CdCl2), a common heavy metal, and diisobutyl phthalate (DIBP), a common phthalate ester, on human sperm functions necessary for fertilization. After in vitro incubation of spermatozoa with 10 µM CdCl2 or 100 and 200 µM DIBP for 24 h, a significant decrease of sperm progressive and hyperactivated motility was observed. The exposure to each of the two toxic agents also induced spontaneous sperm acrosome reaction and blunted the physiological response to progesterone. Both agents induced an increase of caspase activity suggesting triggering of an apoptotic pathway. Our results suggest that acute exposure of spermatozoa to these pollutants may impair sperm ability to reach and fertilize the oocyte.
Abstract The purpose of this article is to provide a brief review of the principles of motor control and learning. Different models of motor control from historical to contemporary are presented with ...emphasis on the Systems model. Concepts of motor learning including skill acquisition, measurement of learning, and methods to promote skill acquisition by examining the many facets of practice scheduling and use of feedback are provided. A fictional client case is introduced and threaded throughout the article to facilitate understanding of these concepts and how they can be applied to clinical practice.
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•This is a first study on the fatigue behaviour of quenched and partitioned martensitic stainless steels.•Q&P treatment enhances strength-ductility balance of martensitic stainless ...steels, without hindering fatigue performance.•Microstructure affects fatigue behaviour; cracks form and grow along martensite packet and block boundaries.•Small MnS inclusions and prior austenite grain boundaries do not affect fatigue crack formation and propagation.
Recent studies have demonstrated the viability of quenching and partitioning (Q&P) treatment for processing martensitic stainless steels showing an improved balance of high strength and sufficient ductility. However, to date, the fatigue behaviour of these materials has not been explored. This study examines the effect of their complex hierarchic microstructure on high cycle fatigue performance. Three steels with different alloying element contents underwent Q&P processing, resulting in multiphase microstructures rich in retained austenite. High cycle fatigue tests and analysis of fatigue fracture surfaces were performed using SEM and EBSD techniques. The results indicate satisfactory high cycle fatigue performance in Q&P treated martensitic stainless steels, surpassing traditional counterparts. Fatigue cracks predominantly form and propagate along martensite packet and block boundaries, while prior austenite grain boundaries and MnS inclusions have minimal influence on fatigue crack formation and growth. Microplastic deformation at the fatigue crack tip enhances local KAM values and triggers localized transformation of retained austenite grains. It is hypothesized that the developed Q&P treated martensitic stainless steels exhibit improved resistance to low cycle fatigue.
Large animal models of Huntington's disease (HD) may increase the reliability of translating preclinical findings to humans. Long live expectancy offers opportunities particularly for disease ...modifying approaches, but also challenges. The transgenic (tg) HD minipig model assessed in this study exhibits a high genetic homology with humans, similar body weight, and comparable brain structures. To test long-term safety, tolerability, and efficacy of novel therapeutic approaches in this model reliable assessments applicable longitudinally for several years are warranted for all phenotypical domains relevant in HD.
To investigate whether the tests proposed assessing motor, cognitive and behavioral domains can be applied repetitively over a 3-year period in minipigs with acceptable variability or learning effects and whether tgHD minipigs reveal changes in these domains compared to wildtype (wt) minipigs suggesting the development of an HD phenotype.
A cohort of 14 tgHD and 18 wt minipigs was followed for three years. Tests applied every six months included a tongue coordination and hurdle test for the motor domain, a color discrimination test for cognition, and a dominance test for assessing behavior. Statistical analyses were performed using repeated ANOVA for longitudinal group comparisons and Wilcoxon-tests for intra-visit differences between tgHD and wt minipigs.
All tests applied demonstrated feasibility, acceptable variance and good consistency during the three-year period. No significant differences between tgHD and wt minipigs were detected suggesting lack of a phenotype before the age of four years.
The assessment battery presented offers measures in all domains relevant for HD and can be applied in long-term phenotyping studies with tgHD minipigs. The observation of this cohort should be continued to explore the timeline of phenotype development and provide information for future interventional studies.
Parkinson's disease (PD) is a neurodegenerative disease in which the progressive loss of dopaminergic neurons (DA) leads to initially sporadic and eventually widespread damage of the nervous system ...resulting in significant musculoskeletal and cognitive deterioration. Loss of motor function alongside increasing cognitive impairment is part of the natural disease progression. Gait is often considered an automatic activity; however, walking is the result of a delicate balance of multiple systems which maintain the body's center of mass over an ever-changing base of support. It is a complex motor behavior that requires components of attention and memory to prevent falls and injury. In addition, evidence points to the critical role of salient visual information to gait adaptability. There is a growing understanding that treatment for PD needs to address movement as it occurs naturally and walking needs to be practiced in more complex environments than traditional therapy has provided.
In this single-blinded randomized-controlled pilot study, an immersive treadmill training was piloted to determine feasibility and preliminary efficacy on gait and cognition in people with PD. Eighteen participants with Hoehn and Yahr stages I-III PD were randomized to either an intervention or a waitlist control group. Following baseline data collection, the intervention group trained for 30 min, three times/week for 4 weeks on a split belt treadmill combined with a first-person immersive video game targeting visuospatial skills and working memory. Assessment was repeated after 4 weeks of training for the experimental group and 1-month after baseline for the control group. Primary motor outcomes were captured with the APDM Opal sensors during 6 MWT, TUG, and TUG Cognitive. Secondary outcomes of cognition were measured with the Montreal Cognitive Assessment (MoCA), Verbal Fluency (Fruit, Vegetable, and Animal) and the Symbol Digit Modality Test (SDMT). Within subject differences were calculated using the Wilcoxon Signed Ranked Test and between subject comparisons were analyzed using the Mann Whitney
-test.
This novel treadmill training program was well-tolerated with all participants in the intervention group completing 4 weeks of training three times a week without any adverse effects. After immersive cognitive motor training, the experimental group made clinically relevant improvements in gait speed and walking distance during the 6 MWT while members of the control group showed no change or decreased gait speed and walking distance over the 1-month trial. In addition, the experimental group demonstrated significant improvement for the TUG Cognitive (
= 0.05) and those changes were greater than the control group (between group
= 0.040). The experimental group also improved scores on MoCA (
= 0.007) and SDMT (
= 0.01) cognitive outcome measures while the control group did not.
The use of immersive gaming technology to engage specific areas of cognition related to gait is feasible in PD. The treadmill training program paired with a customized interactive video game improved walking velocity in addition to non-significant but consistent improvements in other gait measures and cognitive performance in participants with early to mid-stage PD.
Background:
Huntington's disease (HD) leads to altered gait patterns and reduced daily-living physical activity. Accurate measurement of daily-living walking that takes into account involuntary ...movements (e.g. chorea) is needed.
Objective:
To evaluate daily-living gait quantity and quality in HD, taking into account irregular movements.
Methods:
Forty-two individuals with HD and fourteen age-matched non-HD peers completed clinic-based assessments and a standardized laboratory-based circuit of functional activities, wearing inertial measurement units on the wrists, legs, and trunk. These activities were used to train and test an algorithm for the automated detection of walking. Subsequently, 29 HD participants and 22 age-matched non-HD peers wore a tri-axial accelerometer on their non-dominant wrist for 7 days. Measures included gait quantity (e.g., steps per day), gait quality (e.g., regularity) metrics, and percentage of walking bouts with irregular movements.
Results:
Measures of daily-living gait quantity including step counts, walking time and bouts per day were similar in HD participants and non-HD peers (
p
> 0.05). HD participants with higher clinician-rated upper body chorea had a greater percentage of walking bouts with irregular movements compared to those with lower chorea (
p
= 0.060) and non-HD peers (
p
< 0.001). Even after accounting for irregular movements, within-bout walking consistency was lower in HD participants compared to non-HD peers (
p
< 0.001), while across-bout variability of these measures was higher (
p
< 0.001). Many of the daily-living measures were associated with disease-specific measures of motor function.
Conclusions:
Results suggest that a wrist-worn accelerometer can be used to evaluate the quantity and quality of daily-living gait in people with HD, while accounting for the influence of irregular (choreic-like) movements, and that gait features related to within- and across-bout consistency markedly differ in individuals with HD and non-HD peers.
STUDY QUESTION
Is CatSper1 expression in human spermatozoa related to semen parameter values and sperm functions?
SUMMARY ANSWER
CatSper1 expression is positively related to progressive and ...hyperactivated (HA) motility, Ca2+i responsiveness to progesterone but not the acrosome reaction (AR).
WHAT IS KNOWN ALREADY
The role of cationic channel of sperm (CatSper) in sperm functions is clear in animal models but less defined in human sperm cells. Current knowledge is mostly based on low specificity CatSper inhibitors showing agonistic and toxic effects on human spermatozoa and is thus of little help in clarifying the role of the CatSper channel in human sperm functions.
STUDY DESIGN, SIZE, DURATION
CatSper1 protein expression was evaluated in 115 men undergoing semen analysis for couple infertility. CatSper1 expression was related to routine semen parameters, motility kinematic parameters and basal and progesterone-stimulated Ca2+i and the AR.
PARTICIPANTS/MATERIALS, SETTING, METHODS
CatSper1 expression was evaluated (n = 85 normozoospermic, n = 30 asthenozoospermic patients) by immunofluorescence coupled to flow cytometry leading to quantitative measurement of the percentage of ejaculated sperm cells expressing the protein. Semen analysis was evaluated according to World Health Organization guidelines. Kinematic parameters were evaluated by a computer-aided sperm analysis system. Ca2+i was measured by a spectrofluorimetric method in fura-2-loaded spermatozoa. The AR was evaluated in live sperm cells by fluorescent-labeled lectin.
MAIN RESULTS AND THE ROLE OF CHANCE
CatSper1 protein expression in spermatozoa was reduced in asthenozoospermic men (mean ± SD: 53.0 ± 15.5%, n = 30 versus 67.9 ± 17.1% in normozoospermic, n = 85, P < 0.01) and was significantly correlated with progressive (r = 0.36, P < 0.001), total (r = 0.35, P < 0.001) and HA (r = 0.41, P < 0.005) motility. In addition to a higher percentage of spermatozoa not expressing CatSper1, asthenozoospermic men showed a large number of spermatozoa with immunofluorescent signal localized outside the principal piece compared with those in normozoospermia. A significant positive correlation was found between CatSper1 protein expression and the increase of Ca2+i in response to progesterone (r = 0.36, P < 0.05, n = 40) but not with basal Ca2+i. No correlation was found with the AR, either basal or in response to progesterone.
LIMITATIONS, REASONS FOR CAUTION
The study is partly descriptive. Furthermore, we cannot rule out the possibility that some round cells remain after a single round of 40% density gradient centrifugation or that this step may have removed some defective or slow swimming sperm, and therefore this preparation may not be representative of the entire sperm sample. Although our data suggest that CatSper1 may be a useful marker for infertility, and a possible contraceptive target, any clinical application is limited without further research.
WIDER IMPLICATIONS OF THE FINDINGS
Our results demonstrate an association of CatSper1 expression with human sperm progressive and HA motility and provide preliminary evidence that lack of expression or mislocalization of CatSper1 in spermatozoa may be involved in the pathogenesis of asthenozoospermia. However, mechanistic studies are needed to confirm that the correlations between CatSper1 expression and sperm functions are causative.
STUDY FUNDING/COMPETING INTEREST(S)
Supported by grants from Ministry of University and Scientific Research (PRIN project to E.B. and FIRB project to S.M.) and by Regione Toscana (to G.F.). L.T. was recipient of a grant from Accademia dei Lincei (Rome, Italy). The authors have no conflicts of interest to declare.
Parkinson's disease (PD) is a complex diagnosis commonly associated with motor dysfunction, but known to comprise cognitive, psychiatric, and mood disturbances as well. Music has been successfully ...used to address motor and non-motor symptoms of PD. Still, little is known about the nature of an individual with PD's experience and relationship with music on conceptual and emotional levels, which may factor into their engagement in music-based techniques to ameliorate impairments. Two surveys were administered to 19 individuals with PD and 15 individuals without PD in order to gauge their subjective impressions and valuations of music. Participants completed The Brief Music Experience Questionnaire (BMEQ), a standard self-report measure pertaining to the role of music in one's life, prior to performing a perception task which involved listening to and making sound adjustments to three music recordings. Following the perception task, a custom Exit Survey was administered to evaluate the experience of listening to and engaging with the music in the perception task. In all six dimensions of the BMEQ, examining aspects of music experience including commitment to music, self-reported musical aptitude, social uplift, affective reactions, positive psychotropic effects, and reactive musical behavior (RMB, pertaining to actions or behaviors in response to music), the mean and the median were greater for the control group than for the PD group, but the difference was only statistically significant in the RMB dimension. On the Exit Survey, both groups assessed recent, specific, and interactive music listening more positively than the imagined, hypothetical or general music experiences addressed on the BMEQ. Additionally, familiarity had a greater effect on listening pleasure for participants with PD than those without PD. We conclude that people with PD may perceive less of an automatic connection between music and activity than their healthy peers. Additionally, they may receive more pleasure and value from music than they anticipate. Taken together, our results suggest that people with PD may require encouragement to participate as well as empowerment to choose familiar selections in order to better access music-based interventions and the benefits they can offer.