Simultaneous production of biosurfactant and extracellular unspecific peroxygenases by Moesziomyces aphidis XM01 enables an efficient strategy for crude oil degradation.

Crude oil is a hazardous pollutant that poses significant and lasting harm to human health and ecosystems. In this study, Moesziomyces aphidis XM01, a biosurfactant mannosylerythritol lipids (MELs)-producing yeast, was utilized for crude oil degradation. Unlike most microorganisms relying on cytochrome P450, XM01 employed two extracellular unspecific peroxygenases, MaUPO.1 and MaUPO.2, with preference for polycyclic aromatic hydrocarbons (PAHs) and n-alkanes respectively, thus facilitating efficient crude oil degradation. The MELs produced by XM01 exhibited a significant emulsification activity of 65.9% for crude oil and were consequently supplemented in an "exogenous MELs addition" strategy to boost crude oil degradation, resulting in an optimal degradation ratio of 72.3%. Furthermore, a new and simple "pre-MELs production" strategy was implemented, achieving a maximum degradation ratio of 95.9%. During this process, the synergistic up-regulation of MaUPO.1, MaUPO.1 and the key MELs synthesis genes contributed to the efficient degradation of crude oil. Additionally, the phylogenetic and geographic distribution analysis of MaUPO.1 and MaUPO.1 revealed their wide occurrence among fungi in Basidiomycota and Ascomycota, with high transcription levels across global ocean, highlighting their important role in biodegradation of crude oil. In conclusion, M. aphidis XM01 emerges as a novel yeast for efficient and eco-friendly crude oil degradation.

Impact of Early Mobilization on Patients With Acute Ischemic Stroke Treated With Thrombolysis or Thrombectomy: A Randomized Controlled Trial.

BACKGROUND: Early mobilization (EM) within 24 to 72 hours post-stroke may improve patients' performance and ability. However, after intravenous thrombolysis (IVT) or mechanical thrombectomy (MT), the increased risk of hemorrhagic complications impacts the implementation of early out-of-bed mobilization. Few studies have investigated EM after IVT or MT for acute ischemic stroke (AIS), and its impact in these patients is unknown. OBJECTIVE: To investigate the effect of EM on AIS treated with IVT or MT.|. METHODS: We recruited 122 patients with first AIS; 60 patients were treated with IVT, and 62 patients were treated with MT. For each IVT and MT cohort, the control groups received standard early rehabilitation, and the intervention groups received an EM protocol. The training lasted 30 minutes/day, 5 days/week until discharge. MAIN OUTCOMES MEASURES: The effectiveness of the interventions was evaluated using the motor domain of the Functional Independence Measure (FIM-motor) and the Postural Assessment Scale for Stroke Patients (PASS) at baseline, 2-week, 4-week, and 3-month post-stroke, the Functional Ambulation Category 2-week post-stroke, and the total length of stay at the stroke center. RESULTS: Both IVT and MT treatment groups showed improved FIM-motor and PASS scores over time; however, only the IVT EM group had significantly improved FIM-motor performance within 1 month after stroke than the control group. Conclusion. An EM protocol with the same intervention time and session frequency per day as in the standard care protocol was effective in improving the functional ability of stroke patients after IVT.

Climate velocities and species tracking in global mountain regions.

Mountain ranges contain high concentrations of endemic species and are indispensable refugia for lowland species that are facing anthropogenic climate change1,2. Forecasting biodiversity redistribution hinges on assessing whether species can track shifting isotherms as the climate warms3,4. However, a global analysis of the velocities of isotherm shifts along elevation gradients is hindered by the scarcity of weather stations in mountainous regions5. Here we address this issue by mapping the lapse rate of temperature (LRT) across mountain regions globally, both by using satellite data (SLRT) and by using the laws of thermodynamics to account for water vapour6 (that is, the moist adiabatic lapse rate (MALRT)). By dividing the rate of surface warming from 1971 to 2020 by either the SLRT or the MALRT, we provide maps of vertical isotherm shift velocities. We identify 17 mountain regions with exceptionally high vertical isotherm shift velocities (greater than 11.67 m per year for the SLRT; greater than 8.25 m per year for the MALRT), predominantly in dry areas but also in wet regions with shallow lapse rates; for example, northern Sumatra, the Brazilian highlands and southern Africa. By linking these velocities to the velocities of species range shifts, we report instances of close tracking in mountains with lower climate velocities. However, many species lag behind, suggesting that range shift dynamics would persist even if we managed to curb climate-change trajectories. Our findings are key for devising global conservation strategies, particularly in the 17 high-velocity mountain regions that we have identified.

Clinical practice and outcomes of preimplantation genetic testing for CMT1A using a novel direct detection method.

Background: Charcot-Marie-Tooth type 1A (CMT1A), the most frequent type of Charcot-Marie-Tooth disease, is mainly caused by a 1.4-Mb duplication containing the PMP22 gene. There is no effective treatment other than general supportive care and symptomatic treatment. Preimplantation genetic testing for monogenic defects (PGT-M) is an alternative approach for obtaining healthy babies. Methods: A new technology and analysis method based on next-generation sequencing (NGS) was developed to detect duplication mutations directly. Simultaneously, aneuploidy and linkage analyses were performed to achieve a comprehensive and accurate embryo diagnosis. Results: Eight couples were recruited in this study; PMP22 duplication was validated in seven couples, and PMP22 splicing mutation was found in one. Forty-five embryos from 12 PGT cycles were successfully detected using this novel method. The direct detection results for all embryos were consistent with the linkage analyses, suggesting a 100 % accuracy rate, and the aneuploidy rate of the biopsied blastocysts was 33.3 %. Eventually, 18 of the 45 diagnosed embryos were deemed suitable for transfer. Four healthy babies from three families were delivered and their genetic status confirmed by amniocentesis. Additionally, there were no adverse effects of anesthesia or increased pregnancy complications during PGT-M in female patients with CMT1A. Conclusions: This study provided a simple, reliable, and efficient method that can directly detect PMP22 mutations based on NGS data and does not require positive family members. A clinical workflow for CMT1A interruption in the offspring before embryo implantation is also summarized.

Prefrontal cortical hemodynamics and functional network organization during Tai Chi standing meditation: an fNIRS study.

Introduction: Tai Chi standing meditation (Zhan Zhuang, also called pile standing) is characterized by meditation, deep breathing, and mental focus based on theories of traditional Chinese medicine. The purpose of the present study was to explore prefrontal cortical hemodynamics and the functional network organization associated with Tai Chi standing meditation by using functional near-infrared spectroscopy (fNIRS). Methods: Twenty-four channel fNIRS signals were recorded from 24 male Tai Chi Quan practitioners (54.71 ± 8.04 years) while standing at rest and standing during Tai Chi meditation. The general linear model and the SPM method were used to analyze the fNIRS signals. Pearson correlation was calculated to determine the functional connectivity between the prefrontal cortical sub-regions. The small world properties of the FC networks were then further analyzed based on graph theory. Results: During Tai Chi standing meditation, significantly higher concentrations of oxygenated hemoglobin were observed in bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), frontal eye field (FEF), and pre-motor cortex (PMC) compared with the values measured during standing rest (p < 0.05). Simultaneously, significant decreases in deoxygenated hemoglobin concentration were observed in left VLPFC, right PMC and DLPFC during Tai Chi standing meditation than during standing rest (p < 0.05). Functional connectivity between the left and right PFC was also significantly stronger during the Tai Chi standing meditation (p < 0.05). The functional brain networks exhibited small-world architecture, and more network hubs located in DLPFC and VLPFC were identified during Tai Chi standing meditation than during standing rest. Discussion: These findings suggest that Tai Chi standing meditation introduces significant changes in the cortical blood flow and the brain functional network organization.

A novel embryo biopsy morphological analysis and genetic integrality criterion system significantly improves the outcome of preimplantation genetic testing.

PURPOSE: While efforts have been made to establish blastocyst grading systems in the past decades, little research has examined the quality of biopsy specimens. This study is the first to correlate the morphology of biopsied trophectoderm (TE) cells to their quality and subsequent genetic testing results of preimplantation genetic testing (PGT), through an innovative Morphological Analysis and Genetic Integrality Criterion (MAGIC) system. METHODS: Biopsied TE cells were first evaluated according to the MAGIC procedure, followed by whole-genome amplification (WGA) and library construction, and then sequenced using the Illumina X Ten Platform. Copy number variation (CNV) and allele drop-out (ADO) rates as well as test failure rates were compared and analyzed. RESULTS: Our data explores the relationship between TE cell morphology and its quality and final genetic testing outcome, which is established based on the MAGIC system. MAGIC guarantees that only high- or good-quality TE cells are used for genetic testing to generate excellent data uniformity and lower ADO rates. Low-quality cells containing biopsied TE cell mass are responsible for the "background noise" of CNV analysis. CONCLUSION: The MAGIC application has effectively decreased the false-positive mosaicism, hence to ensure the stability and veracity of detection results, to avoid misdiagnoses, and to improve accuracy, as well as to avoid re-biopsy procedures. The study also contributes to understand how the IVF laboratory and the molecular biology laboratory depend on each other to achieve good-quality PGT results, which are clinically relevant for the patients.

Application of the PGT-M strategy using single sperm and/or affected embryos as probands for linkage analysis in males with hereditary tumor syndromes without family history.

Hereditary tumor syndromes have garnered substantial attention due to their adverse effects on both the physical and psychological health of patients, as well as the elevated risk of transmission to subsequent generations. This has prompted a growing interest in exploring preimplantation genetic testing (PGT) as a treatment option to mitigate and eliminate these impacts. Several studies have demonstrated that de novo variants have become a great cause of many hereditary tumor syndromes, which introduce certain difficulties to PGT. In the absence of adequate genetic linkage information (parents and offspring), haplotype construction seems unrealizable. In the study, researchers used single sperm or affected embryos as proband to perform single-nucleotide polymorphism linkage analysis for cases with de novo variants. For complicated variants, the strategy that sperm combined with embryo detection will increase accuracy while avoiding the limitations and potential failures of using a single detection material. The study recruited 11 couples with male de novo carriers, including 3 tumor types and 4 genes. To date, 4 couples have been clinically confirmed as pregnant and three healthy babies have been born. The results of amniocentesis or umbilical cord blood verification were consistent with the results of PGT-M. The study aims to introduce the application of the PGT-M strategy in hereditary tumor syndromes.

Precisely Amplifying Intracellular Oxidative Storm by Metal-Organic Coordination Polymers to Augment Anticancer Immunity.

Oxidative stress accompanying the reactive oxygen species (ROS) burst governs immunocyte infiltration, activation, and differentiation in tumor microenvironments and thus can elicit robust antitumor immunity. Here, we identify a photoactive metal-organic coordination polymer (MOCP), composed of an organometallic core formed by cytotoxic mitoxantrone (MTX) acylates and photosensitive Ru(BIQ)-HDBB [BIQ = 2,2'-biquinoline, HDBB = 4,4'-di(4-benzoato)-2,2'-bipyridine] linked by Fe(II) ions via coordinate covalent bonds and an amphipathic shell encapsulating cholesterol-modified siRNA against GPX4 (siGPX4) via hydrophobic force, to precisely amplify intracellular oxidative storm. MOCPs simultaneously encapsulated MTX, Ru, and siGPX4 with efficiencies >98% and loaded Fe with efficiencies of ∼0.49%. With longer blood circulation and higher tumor accumulation, MOCPs with a 670 nm LED irradiation generate abundant ROS to induce biomembrane dysfunction and subsequently contribute to ferroptotic and immunogenic cell death, which drive tumor-associated antigen-specific immunity. MTX analogs contributed to Type I immunogenic cell death (ICD), while oxidative storm served as a damager for endo/lysosomal escape, an initiator for ferroptosis, and an inducer for type II ICD. Moreover, the blockade of CD73 that reduces extoATP catabolism unleashes immunosuppression, finally enhancing antitumor immune stimulation of MOCPs to promote orthotopic mammary cancer regression and prevent postoperative advanced cancer from recurrence and metastasis. MOCPs by exposing sufficient antigenicity thus provide a platform to synergize immune checkpoint inhibitors for the treatment of immunologically cold tumors.

Efficacy and safety of different doses of epidural morphine coadministered with low-concentration ropivacaine after cesarean section: A retrospective cohort study.

Objective: The optimal dose of epidural morphine after cesarean section (CS) still remains unknown when combined with low-concentration ropivacaine based on a continuous basal infusion (CBI) mode. The aim of this study was to assess the impact of different dose of epidural morphine plus ropivacaine on maternal outcomes. Materials and methods: Data of parturients who received epidural analgesia for CS at a teaching hospital from March 2021 to June 2022 were retrospectively collected. Parturients were divided into two groups (RM3 group and RM6 group) according to different medication regimens of morphine. The implementation of epidural analgesia was performed with 3 mg morphine in RM3 group and 6 mg morphine in RM6 group in combination with 0.1% ropivacaine via a CBI pump. The primary outcomes included pain intensity at rest and movement and the incidence of urinary retention and pruritus within postoperative 48 h. The secondary outcomes included the incidence and severity of postoperative nausea and vomiting (PONV) and pruritus, the rate of rescue analgesia and grading of motor Block. Results: Totally, 531 parturients were eligible for the final analysis, with 428 and 103 parturients in the RM3 group and RM6 group, respectively. There were no statistically significant differences in the visual analogue scores (VAS) at rest and movement within postoperative 48 h between the two groups (all p > 0.05). Compared with the RM6 group, the incidence of urinary retention was lower in the RM3 group within 48 h after CS (4.0% vs. 8.7%, p = 0.044). No significant difference was found in the incidence and severity of PONV and pruritus, the rate of rescue analgesia and grading of motor block between RM3 and RM6 groups. Conclusion: Epidural 3 mg morphine plus 0.1% ropivacaine in a CBI mode can provide equal efficacy and have lower incidence of urinary retention compared with 6 mg morphine after CS.

Differences in muscle coordination between older men and women during brisk walking.

Brisk walking is a highly recommended physical activity for healthy community-dwelling older adults. The objective of this study was to examine through principal component analysis (PCA) how muscle coordination differs between older women and men during brisk walking. Thirty-five healthy older adults (65.2 ± 3.0 years old, 18 females, and 17 males) participated in the study. Eight surface electromyographic electrodes were used to record lower extremity muscle activities, and four inertial measurement unit sensors to monitor hip, knee, and ankle motion. Energy expenditure and heart rate were also measured during brisk walking. The effects of a person's sex on muscle coordination were identified through wavelet and PCA analysis of the sEMG signals. The results of energy expenditure and heart rate confirmed that brisk walking exercise is beneficial for older adults. PCA analysis showed that muscle coordination patterns differ between older women and men: during the stance phase a greater co-contraction of tibialis anterior and soleus in the men, and a greater activation of the quadriceps muscles during the loading-response phase in the women. The wavelet and PCA analyses facilitated a quantitative appraisal of sex-specific differences in the muscle coordination patterns of older men and women during brisk walking.

Preimplantation genetic testing for structural rearrangement based on low-coverage next-generation sequencing accurately discriminates between normal and carrier embryos for patients with translocations.

RESEARCH QUESTION: Can preimplantation genetic testing for structural rearrangement (PGT-SR) based on low-coverage next-generation sequencing (NGS) accurately discriminate between normal and carrier embryos of reciprocal translocation (RecT) and Robertsonian translocation (RobT)? DESIGN: A total of 109 couples with RecT or RobT were included in this study. The ages, bad obsteric histories (BOH), blood karyotype and IVF cycle information, including the number of cumulus-oocyte complexes, metaphase II oocytes, two pronuclei oocytes and blastocysts were recorded. 0.1 × whole genome sequencing (WGS) of embryos followed by copy number variation (identifying unbalanced/balanced) and 2 × WGS of parents and embryos followed by haplotype analysis (discriminating between normal and carrier) were carried out in PGT-SR cycles. The embryos without translocation were transferred and clinical outcomes evaluated. RESULTS: Among all the couples in this study, 67 patients had RecT and 42 had RobT. After unbalanced and balanced detection, 103 balanced embryos underwent a further normal and carrier discrimination procedure, and 53 normal embryos were identified. Finally, 32 normal embryos were transferred, with an ongoing pregnancy rate of 46.88% (15/32). All ongoing pregnancies underwent amniocentesis, and the amninocentesis karyotyping results showed 100% concordance with PGT-SR diagnosis. CONCLUSIONS: Our low-coverage NGS-based PGT-SR method can accurately discriminate between normal and carrier status of balanced embryos. The method is cost-effective and has broad clinical applicability.

Functional mobility effects of progressive early mobilization protocol on people with moderate-to-severe traumatic brain injury: A pre-post intervention study.

BACKGROUND: Brain plasticity evoked by environmental enrichment through early mobilization may improve sensorimotor functions of patients with moderate-to-severe traumatic brain injury (TBI). Increasing evidence also suggests that early mobilization increases verticalization, which is beneficial to TBI patients in critical care. However, there are limited data on early mobilization interventions provided to patients with moderate-to-severe TBI. OBJECTIVE: We investigated the possible enhancing effects of revised progressive early mobilization on functional mobility and the rate of out-of-bed mobility attained by patients with moderate-to-severe TBI. METHODS: This is a quantitative study with a retrospective and prospective pre-post intervention design. We implemented a revised progressive early mobilization protocol for patients with moderate-to-severe TBI admitted to the trauma intensive care unit (ICU) within the previous seven days. The outcome parameters were the rate of patients attaining early mobilization (sitting on the edge of the bed) and the Perme ICU Mobility Score at discharge from the ICU. The outcome parameters in the intervention cohort were compared with those from a historical control cohort who received standard medical care a year previously. Differences in the Perme ICU Mobility Score between the two cohorts were assessed using univariate analysis of covariance. RESULTS: Forty-two patients were included in the progressive early mobilization program and were compared with 44 patients who underwent standard medical care. In the intervention cohort, 100% and 57.2% of the patients completed early rehabilitation and early mobilization, respectively, compared to 0% in the control cohort. The intervention cohort at ICU discharge showed significantly improved the Perme ICU Mobility Scores. CONCLUSIONS: The implementation of the revised progressive early mobilization program for patients with moderate-to-severe TBI resulted in significantly improved mobility at ICU discharge; however, the length of overall stay in the ICU may be not affected.

Effects of acute exercise on craving and cortical hemodynamics under drug-cue exposure in MA-dependent individuals.

BACKGROUND: Methamphetamine (MA) dependent individuals who want to break free of their drug habit or guard against a relapse often find it hard to overcome cravings induced by drug-related cues they are bound to encounter. The purpose of this study was to investigate the effects of acute virtual reality (VR) enhanced physical exercise on cue-induced cravings in MA-dependent individuals. METHODS: Thirty MA-dependent individuals performed a drug-cue reactivity task both before and after a 10 min VR-enhanced competitive cycling exercise. Functional near-infrared spectroscopy (fNIRS) was recorded during the pre- and post-exercise drug-cue reactivity tasks. RESULTS: MA dependent individuals show higher hemodynamic responses in prefrontal cortex (PFC) to drug-related cues than to neutral cues. After acute exercise, hemodynamic responses in PFC, including bilateral dorsolateral prefrontal cortex and orbitofrontal cortex, were attenuated under the same drug-related cues exposure. Acute exercise also affected the functional connectivity between PFC and motor cortex in response to drug-related cues versus neutral cues. CONCLUSIONS: These results suggest that a single session of VR-enhanced competitive cycling exercise facilitates MA-dependent individuals' self-control over their cue-induced cravings by modulating cortical activations and brain functional networks.

A Comparison of the Clinical Effectiveness Between Low-Dose Strong Opioids and Non-Steroidal Anti-Inflammatory Drugs in the Treatment of Mild Cancer Pain: A Randomized Trial.

OBJECTIVE: The present study aims to explore the effectiveness and safety of low-dose strong opioids compared with non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of mild cancer pain. METHODS: From September 2016 to September 2018, 66 patients with a malignant tumor and mild cancer pain admitted to the Department of Oncology of Dalian Fifth People's Hospital were divided into the group A (treated with ibuprofen sustained-release tablets for pain relief) and the group B (treated with oxycodone hydrochloride sustained-release tablets for pain relief). After 7 days of treatment, the pain relief (Numeric Rating Scale [NRS]), physical strength, quality of life scores (Zubrod/ECOG/WHO [ZPS]), the Edmonton Symptom Assessment System [ESAS], and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core15-Palliative [EORTC QLQ-C15-PAL] scores), and the occurrence of adverse reactions between the two groups were compared. The occurrence of adverse reactions in the mid-term (after one month and three months of treatment) between the two groups were also compared. RESULTS: Both groups had over 90% analgesic efficiency, but complete pain relief was more likely to be obtained in the group B (41.18%). The total analgesic efficiency in the group B was higher (100%) than in the group A (98.9%), and the difference was statistically significant (P < 0.05). The differences in the physical strength and quality of life scores in the two groups before and after treatment were statistically significant (P < 0.05). The differences in the ZPS scores between the two groups were statistically significant (P < 0.05). The differences in ESAS and EORTC QLQ-C15-PAL scores between groups were not statistically significant (P > 0.05). CONCLUSION: The application of low-dose oxycodone hydrochloride sustained-release tablets as the initial medication for patients with mild cancer pain was safe and effective, and the adverse reactions were easy to manage.

The Effect of Fatigue on Wheelchair Users' Upper Limb Muscle Coordination Patterns in Time-Frequency and Principal Component Analysis.

An assessment of shoulder muscle coordination patterns is important to gain insight into muscle fatigue during wheelchair propulsion. The objective of the present study was to quantify muscle coordination changes over time during fatiguing wheelchair propulsion, as the muscles go through distinct levels of fatigue, a) non-fatigued, b) transiting to fatigue and c) fatigued to exhaustion. We recorded surface electromyography (sEMG) signals of the anterior deltoid (AD), middle deltoid (MD), posterior deltoid (PD), infraspinatus (IS), upper trapezius (UT), sternal head of the pectoralis major (PM), biceps brachii (BB), and triceps brachii (TB) during a wheelchair incremental exercise test. Nine wheelchair users with a diagnosis of spina bifida or T6-T12 spinal cord injury volunteered for the study. Oxygen uptake and SmartWheel kinetic parameters were also recorded during the test. EMG signals were processed by wavelet and principal component analysis (PCA), allowing for an assessment of how wheelchair users modify their muscle coordination patterns over time. Analyses of covariance (ANCOVA) were conducted to identify the main effect of fatigue levels on muscle coordination patterns by controlling for the effect of increased workload as covariate. A significant effect of fatigue levels on the PC1 and PC3 loading scores was found after controlling for the effect of increasing workloads (with both cases). In addition, PC3 reflects the most dominant fatigue effect on muscle coordination patterns which are not affected by increased ergometer workload. PC3 indicates muscle imbalance when muscles are fully fatigued and muscle co-contraction when muscles are beginning to fatigue. We conclude that fatigue-related changes in neuromuscular activity during wheelchair propulsion contribute to muscle imbalance and reflect a strategy of stiffening the shoulder joint.

Effects of early mobilization on short-term blood pressure variability in acute intracerebral hemorrhage patients: A protocol for randomized controlled non-inferiority trial.

BACKGROUND: Early out-of-bed mobilization may improve acute post-intracerebral hemorrhage (ICH) outcomes, but hemodynamic instability may be a concern. Some recent studies have showed that an increase in mean systolic blood pressure (SBP) and high blood pressure variability (BPV), high standard deviation of SBP, may lead to negative ICH outcomes. Therefore, we investigated the impact of an early mobilization (EM) protocol on mean SBP and BPV during the acute phase. METHODS: The study was an assessor-blinded, randomized controlled non-inferiority study. The participants were in An Early Mobilization for Acute Cerebral Hemorrhage trial and were randomly assigned to undergo EM or a standard early rehabilitation (SER) protocol within 24 to 72 hour after ICH onset at the stroke center. The EM and SER groups each had 30 patients. 24-measurement SBP were recorded on days 2 and 3 after onset, and SBP were recorded three times daily and during rehabilitation on days 4 through 7. The two groups' mean SBP and BPV under three different time frames (days 2 and 3 during the acute phase, and days 4 through 7 during the late acute phase) were calculated and compared. RESULTS: At baseline, the two groups' results were similar, with the exception being that the mean time to first out-of-bed mobilization after symptom onset was 51.60 hours (SD 14.15) and 135.02 hours (SD 33.05) for the EM group and SER group, respectively (P < .001). There were no significant differences in mean SBP and BPV during the acute and late acute phase between the two groups for the three analyses (days 2, 3, and 4 through 7) (P > .05). CONCLUSIONS: It is safe to implement the EM protocol within 24 to 72 hour of onset for mild-moderate ICH patients during the acute phase.

A comprehensive PGT-M strategy for ADPKD patients with de novo PKD1 mutations using affected embryo or gametes as proband.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease characterized by the development of renal cysts and progression to renal failure. Preimplantation genetic testing-monogenic disease (PGT-M) is an alternative option to obtain healthy babies. However, de novo PKD1 mutation of one of the spouses or the absence of a positive family history poses a serious challenge to PGT-M. Here, we described a comprehensive strategy which includes preimplantation genetic testing for aneuploidies (PGT-A) study and monogenic diagnosis study for ADPKD patients bearing de novo mutations. The innovation of our strategy is to use the gamete (polar body or single sperm) as proband for single-nucleotide polymorphism (SNP) linkage analysis to detect an embryo's carrier status. Nine ADPKD couples with either de novo mutation or without a positive family history were recruited and a total of 34 embryos from 13 PGT-M cycles were examined. Within these nine couples, two successfully delivered healthy babies had their genetic status confirmed by amniocentesis. This study provides a creative approach for embryo diagnosis of patients with de novo mutations or patients who lack essential family members for linkage analysis.

The Effects of Inter-Set Recovery Time on Explosive Power, Electromyography Activity, and Tissue Oxygenation during Plyometric Training.

Performing continuous sets to failure is fatiguing during the plyometric training. Cluster sets have been used to redistribute total rest time to create short frequent sets so that muscle fatigue can be avoided. The purpose of the study was to investigate the effects of inter-set recovery time on lower extremity explosive power, neuromuscular activity, and tissue oxygenation during plyometric exercise and recovery. An integrated assessment of explosive power, muscle electrical activity, and tissue oxygenation was adopted in the present study to help understand local muscle metabolism and fatigue during plyometric exercise and recovery. Ten university male basketball players participated in this study. Subjects performed 4 groups of exercise, each group comprised of 3 sets of jumps: 1, 2, 3, or 5 min. Surface electromyography (sEMG) signals were collected from 9 lower extremity muscles; near-infrared spectroscopy (NIRS) was recorded on vastus lateralis; mechanical data during plyometric exercise were collected from a force plate. No significant differences among sets and among groups were found regarding explosive power, jump height, EMG intensity, mean power frequency, the rate of tissue saturation index, and HbO2 changes between baseline and recovery. The current study has shown no muscular fatigue induced during the 4 groups of exercise. The results of this study may help inform recommendations concerning the recovery time during plyometric exercises at low loads (30% 1 RM).

Clinical application of an NGS-based method in the preimplantation genetic testing for Duchenne muscular dystrophy.

PURPOSE: To determine whether next-generation sequencing (NGS) could be used to directly detect different mutations of Duchenne muscular dystrophy (DMD) during preimplantation genetic testing (PGT). METHODS: From Sep. 2016 to Aug. 2018, a total of six couples participated in this study. Four cases carried DMD exon deletions and two carried exon duplications. Trophectoderm cells were biopsied at day 5 or 6 and NGS was used in the genetic testing of the biopsied cells after whole-genome amplification. We developed a new method-DIRected Embryonic Cell Testing of Exon Deletion/Duplication (DIRECTED) to directly detect the single-gene mutation by NGS. Linage analysis based on single-nucleotide polymorphism (SNP) was used to validate the results from DIRECTED. RESULTS: In the four deletion cases, DIRECTED was used to detect DMD exon deletion in 16 biopsied embryos. All DIRECTED results were consistent with linkage analysis, indicating this method was reliable in detecting deletions around 1 Mb. In the two cases carrying exon duplications, no blastocyst was obtained for biopsy. Nonetheless, preliminary experiment results suggested that DIRECTED could also be used for direct detection of exon duplications in embryos. CONCLUSIONS: Exon deletions or duplications in DMD of preimplantation embryos could be detected directly by NGS-based methods during PGT.