BACKGROUND Sperm DNA fragmentation is a possible predictive parameter for male fertility status. The occurrence of M540 bodies in semen of subfertile subjects affects flow cytometric investigations ...in sperm. We set up a new method to evaluate DNA fragmentation excluding M540 bodies. METHODS DNA fragmentation was evaluated by flow cytometry in semen of 75 subjects both by terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL, traditional method) and by double staining with TUNEL and propidium iodide (PI, new method). RESULTS The use of the new method revealed that TUNEL underestimates sperm DNA fragmentation in flow cytometry and showed two sperm populations stained with low (PIdim) and high (PIbr) avidity for PI. The PIdim population is entirely composed of DNA fragmented sperm and its incidence shows highly significant negative correlations with morphology, motility, sperm count and concentration (respectively, r = −0.51, −0.52, −0.46 and −0.32, n = 75). DNA fragmentation in the PIbr sperm population is independent from semen quality. CONCLUSIONS The correlations between sperm DNA breakage and semen quality previously reported are mainly driven by the occurrence of the PIdim population. DNA fragmented sperm in this population are more likely to have poorer morphology, reduced motility and thus a reduced chance to fertilize an oocyte than DNA damaged sperm in PIbr population. Distinguishing between the two types of sperm DNA fragmentation appears to be important in clinical investigations.
Background
Hyponatremia is associated with negative clinical outcomes even when chronic and mild. It is also known that hyponatremia treatment should be appropriately performed, to avoid dramatic ...consequences possibly leading to death. We have previously demonstrated that chronically low extracellular Na
+
, independently of reduced osmolality, is associated with signs of neuronal cell distress, possibly involving oxidative stress.
Aim
The aim of the present study was to assess whether the return to normal extracellular Na
+
is able to revert neuronal cell damage.
Methods
After exposing SH-SY5Y and SK-N-AS cells to low Na
+
and returning to normal Na
+
, we analyzed cell viability by MTS assay, ROS accumulation by FASCan and expression of anti-apoptotic genes.
Results
We found that the viability of cells was restored upon return to normal Na
+
. However, when more subtle signs of cell distress were assessed, such as the expression level of the anti-apoptotic genes Bcl-2 and DHCR24 or of the heme oxygenase 1 gene, a complete return to basal values was not observed, in particular in SK-N-AS, even when Na
+
was gradually increased. We also demonstrated that the amount of ROS significantly increased in low Na
+
, thus confirming that oxidative stress appears to contribute to the effects of low Na
+
on cell homeostasis.
Conclusions
Overall, this study provided the first demonstration that the correction of chronically low extracellular Na
+
may not be able to revert all the cell alterations associated with reduced Na
+
. These results suggest that prompt hyponatremia treatment might prevent possible residual abnormalities.
Summary
Despite more cancers in young men over the past two decades, improvements in therapies give a greater chance to live full lives following treatment. Sperm genomic quality is variable ...following cancer diagnosis, so its assessment is important if sperm cryopreservation is being considered. Here, we evaluated DNA damage using two DNA damage assays: an alkaline and for the first time, a neutral Comet assays in men presenting with testicular cancer (n = 19 for alkaline and 13 for neutral group) and lymphoma (n = 13 for alkaline and 09 for neutral group) compared with fertile donors (n = 20 for alkaline and 14 for neutral group). No significant differences were observed in any semen analysis parameters. In contrast, sperm DNA damage was higher in men with testicular cancer than in donors as assessed by both the alkaline (12.4% vs. 37.4%, p < 0.001) and neutral (7.5% vs. 13.4%; p < 0.05) Comet assays. Similar trends were observed in men with lymphoma. Here, sperm DNA damage was higher using both the alkaline (35.0% vs. 12.4%) and neutral (10.7% against 7.5% (p < 0.05) Comet assays. Moreover, the DNA strand breaks (particularly double‐strand breaks) were significantly more prominent in men with cancer having abnormal seminal parameters than normozoospermic ones. This study showed that sperm DNA testing using alkaline and neutral Comet assays is more sensitive than semen analysis in detecting impaired sperm quality in men presenting with cancer. It may provide a useful adjunct when considering storage prior to cancer investigations and assisted reproductive techniques (ART)‐based treatment.
Postural control impairments begin early in Huntington's disease yet measures most sensitive to progression have not been identified. The aims of this study were to: 1) evaluate postural control and ...gait in people with and without Huntington's disease using wearable sensors; and 2) identify measures related to diagnosis and clinical severity.
43 individuals with Huntington's disease and 15 age-matched peers performed standing with feet together and feet apart, sitting, and walking with wearable inertial sensors. One-way analysis of variance determined differences in measures of postural control and gait between early and mid-disease stage, and non-Huntington's disease peers. A random forest analysis identified feature importance for Huntington's disease diagnosis. Stepwise and ordinal regressions were used to determine predictors of clinical chorea and tandem walking scores respectively.
There was a significant main effect for all postural control and gait measures comparing early stage, mid stage and non-Huntington's disease peers, except for gait cycle duration and step duration. Total sway, root mean square and mean velocity during sitting, as well as gait speed had the greatest importance in classifying disease status. Stepwise regression showed that root mean square during standing with feet apart significantly predicted clinical measure of chorea, and ordinal regression model showed that root mean square and total sway standing feet together significantly predicted clinical measure of tandem walking.
Root mean square measures obtained in sitting and standing using wearable sensors have the potential to serve as biomarkers of postural control impairments in Huntington's disease.
•Sensor-derived postural control measures are discriminative in Huntington's disease.•Root mean square measures predict disease status and correlate to clinical measures.•Root mean square during sitting and standing are potential disease biomarkers.
Individuals with Huntington's disease (HD) have impairments in performing dual-tasks, however, there is limited information about the effects of changing postural and cognitive demands as well as ...which measures are best suited as markers of underlying motor-cognitive interference.
Forty-three individuals with HD and 15 healthy controls (HC) completed single tasks of walking (Timed Up & Go (TUG), 7 m walk), standing (feet together, feet apart and foam surface) and seated cognitive performance (Stroop, Symbol Digit Modalities Test (SDMT), Delis-Kaplan Executive Function System (DKEFS) Sorting test) and dual cognitive-motor tasks while standing (+ Stroop) and walking (+ DKEFS, TUG cognitive). APDM Opal sensors recorded measures of postural sway and time to complete motor tasks.
Individuals with HD had a greater increase in standing postural sway compared to HC from single to dual-tasks and with changes to support surface. Both groups demonstrated a decrease in gait performance during the TUG cognitive, however, this difference was greater in people with HD compared to HC. While those with HD showed a greater dual-task motor cost compared to HC, both groups behaved similarly as condition complexity increased.
Standing postural sway is a more sensitive marker of instability than change in standard gait speed, particularly under dual-task conditions. The more complex TUG cognitive is a sensitive measure of walking dual-task performance. The results of this study provide insights about the nature of motor-cognitive impairments in HD and provide support for a distinction between static and dynamic postural control mechanisms during performance of dual-tasks.
•Individuals with HD have impairments performing dual-tasks.•In HD, dual-task standing postural sway is a sensitive marker of instability.•The TUG cognitive is a sensitive measure of walking dual-task performance in HD.
This study aimed at evaluating the effects of angiotensin‐converting enzyme inhibitor (enalapril) and angiotensin II antagonist (valsartan) on the oestradiol and progesterone production in ewes ...submitted to oestrous synchronization protocol. The animals were weighed and randomly divided into three groups (n = 7). A pre‐experiment conducted to verify the effectiveness and toxicity of enalapril (0.5 mg/kg LW) and valsartan (2.2 mg/kg LW) showed that, in the doses used, these drugs were effective in reducing blood pressure without producing toxic effects. In the experiment, all animals were subjected to oestrous synchronization protocol during 12 days. On D10, D11 and D12, animals received saline, enalapril or valsartan (same doses of the pre‐experiment), according to the group randomly divided. The hormonal analysis showed an increase in oestradiol on the last day of the protocol (D12) in animals that received enalapril (p < 0.05), but not in other groups, without changing the concentration of progesterone in any of the treatments. It is concluded that valsartan and enalapril are safe and effective subcutaneously for use in sheep and that the angiotensin‐converting enzyme (ACE) inhibition with enalapril leads to an increase in oestradiol production near ovulation without changing the concentration of progesterone. This shows that ACE inhibition may be a useful tool in reproductive biotechnologies involving induction and synchronization of oestrus and ovulation in sheep.
Background
Impaired gait plays an important role for quality of life in patients with Huntington’s disease (HD). Measuring objective gait parameters in HD might provide an unbiased assessment of ...motor deficits in order to determine potential beneficial effects of future treatments.
Objective
To objectively identify characteristic features of gait in HD patients using sensor-based gait analysis. Particularly, gait parameters were correlated to the Unified Huntington’s Disease Rating Scale, total motor score (TMS), and total functional capacity (TFC).
Methods
Patients with manifest HD at two German sites (
n
= 43) were included and clinically assessed during their annual ENROLL-HD visit. In addition, patients with HD and a cohort of age- and gender-matched controls performed a defined gait test (4 × 10 m walk). Gait patterns were recorded by inertial sensors attached to both shoes. Machine learning algorithms were applied to calculate spatio-temporal gait parameters and gait variability expressed as coefficient of variance (CV).
Results
Stride length (− 15%) and gait velocity (− 19%) were reduced, while stride (+ 7%) and stance time (+ 2%) were increased in patients with HD. However, parameters reflecting gait variability were substantially altered in HD patients (+ 17% stride length CV up to + 41% stride time CV with largest effect size) and showed strong correlations to TMS and TFC (0.416 ≤
r
Sp
≤ 0.690). Objective gait variability parameters correlated with disease stage based upon TFC.
Conclusions
Sensor-based gait variability parameters were identified as clinically most relevant digital biomarker for gait impairment in HD. Altered gait variability represents characteristic irregularity of gait in HD and reflects disease severity.
While physical activity (PA) is recognized as important in Huntington's disease (HD) disease management, there has been no long-term evaluation undertaken. We aimed to evaluate the feasibility of a ...nested (within cohort) randomized controlled trial (RCT) of a physical therapist-led PA intervention.
Participants were recruited from six HD specialist centers participating in the Enroll-HD cohort study in Germany, Spain and U.S. Assessments were completed at baseline and 12 months and linked to Enroll-HD cohort data. Participants at three sites (cohort) received no contact between baseline and 12 month assessments. Participants at three additional sites (RCT) were randomized to PA intervention or control group. The intervention consisted of 18 sessions delivered over 12 months; control group participants received no intervention, however both groups completed monthly exercise/falls diaries and 6-month assessments.
274 participants were screened, 204 met inclusion criteria and 116 were enrolled (59 in cohort; 57 in RCT). Retention rates at 12-months were 84.7% (cohort) and 79.0% (RCT). Data completeness at baseline ranged from 42.3 to 100% and at 12-months 19.2–85.2%. In the RCT, there was 80.5% adherence, high intervention fidelity, and similar adverse events between groups. There were differences in fitness, walking endurance and self-reported PA at 12 months favoring the intervention group, with data completeness >60%. Participants in the cohort had motor and functional decline at rates comparable to previous studies.
Predefined progression criteria indicating feasibility were met. PACE-HD lays the groundwork for a future, fully-powered within cohort trial, but approaches to ensure data completeness must be considered.
NCT03344601.
•A 12-month physical activity intervention for Huntington's disease was feasible and safe.•Nesting a trial within a cohort is feasible for long-term physical activity evaluation.•PACE-HD has laid the groundwork for future cohort studies of non-pharmacological interventions.
•Public charging has value to users and can support PEV adoption.•For PHEV, public charging displaces gasoline use.•For BEV, public charging enables additional driving.•Estimate functions of ...willingness to pay for public charging infrastructure.•Existing charging infrastructure in CA is worth thousands of dollars per user.
Lack of charging infrastructure is an important barrier to the growth of the plug-in electric vehicle (PEV) market. Public charging infrastructure has tangible and intangible value, such as reducing range anxiety or building confidence in the future of the PEV market. Quantifying the value of public charging infrastructure can inform analysis of investment decisions and can help predict the impact of charging infrastructure on future PEV sales. Estimates of willingness to pay (WTP) based on stated preference surveys are limited by consumers’ lack of familiarity with PEVs. As an alternative, we focus on quantifying the tangible value of public PEV chargers in terms of their ability to displace gasoline use for PHEVs and to enable additional electric (e−) vehicle miles for BEVs, thereby mitigating the limitations of shorter range and longer recharging time. Simulation studies provide data that can be used to quantify e-miles enabled by public chargers and the value of additional e-miles can be inferred from econometric estimates of WTP for increased vehicle range. Functions are synthesized that estimate the WTP for public charging infrastructure by plug-in hybrid and battery electric vehicles, conditional on vehicle range, annual vehicle travel, pre-existing charging infrastructure, energy prices, vehicle efficiency, and household income. A case study based on California’s public charging network in 2017 indicates that, to the purchaser of a new BEV with a 100-mile range and home recharging, existing public fast chargers are worth about $1500 for intraregional travel, and fast chargers along intercity routes are valued at over $6500.
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