Low-intensity pulsed ultrasound ameliorates glia-mediated inflammation and neuronal damage in experimental intracerebral hemorrhage conditions.

BACKGROUND: Intracerebral hemorrhage (ICH) is a condition associated with high morbidity and mortality, and glia-mediated inflammation is a major contributor to neurological deficits. However, there is currently no proven effective treatment for clinical ICH. Recently, low-intensity pulsed ultrasound (LIPUS), a non-invasive method, has shown potential for neuroprotection in neurodegenerative diseases. This study aimed to investigate the neuroprotective effects and potential mechanisms of LIPUS on glia-mediated inflammation in ICH. METHODS: This study used 289 mice to investigate the effects of LIPUS on ICH. ICH was induced by injecting bacterial collagenase (type VII-S; 0.0375 U) into the striatum of the mice. LIPUS was applied noninvasively for 3 days, including a 2-h-delayed intervention to mimic clinical usage. The study evaluated neurological function, histology, brain water content, hemoglobin content, MRI, and protein expression of neurotrophic factors, inflammatory molecules, and apoptosis. In vitro studies investigated glia-mediated inflammation by adding thrombin (10 U/mL) or conditioned media to primary and cell line cultures. The PI3K inhibitor LY294002 was used to confirm the effects of PI3K/Akt signaling after LIPUS treatment. RESULTS: LIPUS treatment improved neurological deficits and reduced tissue loss, edema, and neurodegeneration after ICH. The protective effects of LIPUS resulted from decreased glia-mediated inflammation by inhibiting PI3K/Akt-NF-κB signaling, which reduced cytokine expression and attenuated microglial activation-induced neuronal damage in vitro. CONCLUSIONS: LIPUS treatment improved neurological outcomes and reduced glia-mediated inflammation by inhibiting PI3K/Akt-NF-κB signaling after ICH. LIPUS may provide a non-invasive potential management strategy for ICH.

Performance Evaluation for Clinical Stroke Rehabilitation via an Automatic Mobile Gait Trainer.

This paper investigates the clinical efficacy of an automatic mobile trainer for gait training in stroke patients. Neuro-Developmental Treatment (NDT) is a rehabilitation method for stroke patients that enhances motor learning through repeated practice. Despite the proven effectiveness of therapist-assisted NDT, it is labor-intensive and demands health resources. Therefore, we developed automatic trainers based on NDT principles to perform gait training. This paper modifies the mobile trainer's intervention patterns to improve the subject's longitudinal gait symmetry, lateral pelvic displacement symmetry, and pelvic rotation. We first invited ten healthy subjects to test the modified trainer and then recruited 26 stroke patients to undergo the same gait training. Longitudinal symmetry, lateral symmetry, and pelvic rotation were assessed before, during, and after the intervention. Most subjects show improvements in longitudinal symmetry, lateral symmetry, and pelvic rotation after using the trainer. These results confirm the trainer's effectiveness of the modified intervention schemes in helping clinical gait rehabilitation for stroke patients.

Evaluation of post-stroke spasticity from the subacute to chronic stages: A clinical and neurophysiologic study of motoneuron pool excitability.

Spasticity measured using clinical scales, such as the modified Ashworth scale (MAS), may not sufficiently evaluate the effectiveness of therapeutic interventions and predict prognosis. This study aimed to compare changes in H-reflex excitability in the spastic and unimpaired upper and lower limbs of patients with acute and chronic stroke. We also investigated the relationship between the degree of spasticity as assessed by the MAS and motor neuron pool excitability with by analyzing H-reflex excitability. Sixty adult patients with a first-ever stroke were recruited for this study. MAS scores were recorded in the post-stroke upper and lower limb muscles. H-reflexes and M-responses of the bilateral flexor carpi radialis and soleus were tested by stimulating the median and tibial nerves. The results showed that both the ratio of the maximal size of the H-reflex (Hmax) to the maximal size of the M-response (Mmax) and the ratio of the developmental slope of H-reflex (Hslp) to that of the M-responses (Mslp) were significantly higher on the spastic side than on the unimpaired side for the upper and lower limbs. In contrast, the ratio of the threshold of the H-reflex (Hth) to the threshold of the M-response (Mth) only showed significant differences between the two sides in the upper limbs. The Hslp/Mslp paretic/non-paretic ratio was increased in patients with MAS scores of 2 or 3 compared to MAS scores of 1 for both the upper and lower limbs, whereas the Hmax/Mmax paretic/non-paretic ratio showed significant differences between MAS scores of 2 or 3 and 1 only in the upper limbs. Moreover, in either the spastic or unimpaired sides, there were no significant differences in any of the three motoneuron pool excitability parameters, Hmax/Mmax, Hslp/Mslp, and Hth/Mth, between the shorter chronicity (time post-stroke ≤6 months) and longer chronicity groups (time post-stroke >6 months) for both the upper and lower limbs. These results suggest that Hslp/Mslp could be a potential neurophysiological indicator for evaluating the degree of spasticity in both the upper and lower limbs of patients with hemiplegia. The MAS and Hslp/Mslp characterize clinical and neurophysiologic spasticity, respectively, and could be used as an integrated approach to evaluate and follow up post-stroke spasticity.

Superior Gait Symmetry and Postural Stability among Yoga Instructors-Inertial Measurement Unit-Based Evaluation.

This study investigates gait symmetry and single-leg stance balance of professional yoga instructors versus age-matched typically developed controls using inertial measurement unit (IMU)-based evaluation. We recruited twenty-five yoga instructors and twenty-five healthy control subjects to conduct the walking experiments and single-leg stance tests. Kinematic data were measured by attaching IMUs to the lower limbs and trunk. We assessed the asymmetry of swing phases during the normal-walk and tandem-walk tests with eyes open and closed, respectively. The subjects subsequently conducted four single-leg stance tests, including a single-leg stance on both legs with eyes open and closed. Two balance indexes regarding the angular velocities of the waist and chest were defined to assess postural stability. The gait asymmetry indexes of yoga instructors were significantly lower than those of the typically developed controls. Similarly, the yoga instructors had better body balance in all four single-leg stance tests. This study's findings suggest that yoga improves gait asymmetry and balance ability in healthy adults. In the future, further intervention studies could be conducted to confirm the effect of yoga training.

Detection and Classification of Stroke Gaits by Deep Neural Networks Employing Inertial Measurement Units.

This paper develops Deep Neural Network (DNN) models that can recognize stroke gaits. Stroke patients usually suffer from partial disability and develop abnormal gaits that can vary widely and need targeted treatments. Evaluation of gait patterns is crucial for clinical experts to make decisions about the medication and rehabilitation strategies for the stroke patients. However, the evaluation is often subjective, and different clinicians might have different diagnoses of stroke gait patterns. In addition, some patients may present with mixed neurological gaits. Therefore, we apply artificial intelligence techniques to detect stroke gaits and to classify abnormal gait patterns. First, we collect clinical gait data from eight stroke patients and seven healthy subjects. We then apply these data to develop DNN models that can detect stroke gaits. Finally, we classify four common gait abnormalities seen in stroke patients. The developed models achieve an average accuracy of 99.35% in detecting the stroke gaits and an average accuracy of 97.31% in classifying the gait abnormality. Based on the results, the developed DNN models could help therapists or physicians to diagnose different abnormal gaits and to apply suitable rehabilitation strategies for stroke patients.

Activation of TrkB/Akt signaling by a TrkB receptor agonist improves long-term histological and functional outcomes in experimental intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) induces a complex sequence of apoptotic cascades that contribute to secondary neuronal damage. Tropomyosin-related kinase receptor B (TrkB) signaling plays a crucial role in promoting neuronal survival following brain damage. METHODS: The present study investigated the protective effects and underlying mechanisms of TrkB activation by the specific TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), in a model of collagenase-induced ICH and in neuronal cultures. Mice subjected to collagenase-induced ICH were intraperitoneally injected with either 7,8-DHF or vehicle 10 min after ICH and, subsequently, daily for 3 days. Behavioral studies, brain edema measurement, and histological analysis were conducted. Levels of TrkB signaling-related molecules and apoptosis-related proteins were analyzed by western blots. RESULTS: Treatment with 20 mg/kg 7,8-DHF significantly improved functional recovery and reduced brain damage up to 28 days post-ICH. Reduction in neuronal death, apoptosis, and brain edema were also observed in response to 7,8-DHF treatment at 3 days post-ICH. These changes were accompanied by a significant increase in the phosphorylation of TrkB and Akt (Ser473/Thr308) at 1 and 3 days, but had no effect on Erk 44/42 phosphorylation. 7,8-DHF also enhanced the phosphorylation of Ask-1 Ser967 and FOXO-1, downstream targets of Akt at 1 and 3 days. Moreover, 7,8-DHF increased brain-derived neurotrophic factor levels at 1 day. In primary cultured neurons stimulated with hemin, 7,8-DHF promoted survival and reduced apoptosis. Furthermore, delaying the administration of 7,8-DHF to 3 h post-ICH reduced brain tissue damage and neuronal death. CONCLUSIONS: Our findings demonstrate that the activation of TrkB signaling by 7,8-DHF protects against ICH via the Akt, but not the Erk, pathway. These data provide new insights into the role of TrkB signaling deficit in the pathophysiology of ICH and highlight TrkB/Akt as possible therapeutic targets in this disease.

Increased Soluble Epoxide Hydrolase in Human Gestational Tissues from Pregnancies Complicated by Acute Chorioamnionitis.

Chorioamnionitis (CAM) is primarily a polymicrobial bacterial infection involving chorionic and amniotic membranes that is associated with increased risk of preterm delivery. Epoxyeicosatrienoic acids (EETs) are eicosanoids generated from arachidonic acid by cytochrome P450 enzymes and further metabolized mainly by soluble epoxide hydrolase (sEH) to produce dihydroxyeicosatrienoic acids (DHETs). As a consequence of this metabolism of EETs, sEH reportedly exacerbates several disease states; however, its role in CAM remains unclear. The objectives of this study were to (1) determine the localization of sEH and compare the changes it undergoes in the gestational tissues (placentas and fetal membranes) of women with normal-term pregnancies and those with pregnancies complicated by acute CAM; (2) study the effects of lipopolysaccharide (LPS) on the expression of sEH in the human gestational tissues; and (3) investigate the effect of 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a specific sEH inhibitor, on LPS-induced changes in 14,15-DHET and cytokines such as interleukin- (IL-) 1ß and IL-6 in human gestational tissues in vitro and in pregnant mice. We found that women with pregnancies complicated by acute CAM had higher levels of sEH mRNA and protein in fetal membranes and villous tissues compared to those in women with normal-term pregnancies without CAM. Furthermore, fetal membrane and villous explants treated with LPS had higher tissue levels of sEH mRNA and protein and 14,15-DHET than those present in the vehicle controls, while the administration of AUDA in the media attenuated the LPS-induced production of 14,15-DHET in tissue homogenates and IL-1ß and IL-6 in the media of explant cultures. Administration of AUDA also reduced the LPS-induced changes of 14,15-DHET, IL-1ß, and IL-6 in the placentas of pregnant mice. Together, these results suggest that sEH participates in the inflammatory changes in human gestational tissues in pregnancies complicated by acute CAM.

Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase reduces brain damage and attenuates neuroinflammation after intracerebral hemorrhage.

BACKGROUND: Inflammatory responses significantly contribute to neuronal damage and poor functional outcomes following intracerebral hemorrhage (ICH). Soluble epoxide hydrolase (sEH) is known to induce neuroinflammatory responses via degradation of anti-inflammatory epoxyeicosatrienoic acids (EET), and sEH is upregulated in response to brain injury. The present study investigated the involvement of sEH in ICH-induced neuroinflammation, brain damage, and functional deficits using a mouse ICH model and microglial cultures. METHODS: ICH was induced by injecting collagenase in both wild-type (WT) C57BL/6 mice and sEH knockout (KO) mice. WT mice were injected intracerebroventricularly with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor, 30 min before ICH. Expression of sEH in the hemorrhagic hemisphere was examined by immunofluorescence and Western blot analysis. The effects of genetic deletion or pharmacological inhibition of sEH by AUDA on neuroinflammatory responses, EET degradation, blood-brain barrier (BBB) permeability, histological damage, and functional deficits were evaluated. The anti-inflammatory mechanism of sEH inactivation was investigated in thrombin- or hemin-stimulated cultured microglia. RESULTS: ICH induced an increase in sEH protein levels in the hemorrhagic hemisphere from 3 h to 4 days. sEH was expressed in microglia/macrophages, astrocytes, neurons, and endothelial cells in the perihematomal region. Genetic deletion of sEH significantly attenuated microglia/macrophage activation and expression of inflammatory mediators and reduced EET degradation at 1 and 4 days post-ICH. Deletion of sEH also reduced BBB permeability, matrix metalloproteinase (MMP)-9 activity, neutrophil infiltration, and neuronal damage at 1 and 4 days. Likewise, administration of AUDA attenuated proinflammatory microglia/macrophage activation and EET degradation at 1 day post-ICH. These findings were associated with a reduction in functional deficits and brain damage for up to 28 days. AUDA also ameliorated neuronal death, BBB disruption, MMP-9 activity, and neutrophil infiltration at 1 day. However, neither gene deletion nor pharmacological inhibition of sEH altered the hemorrhage volume following ICH. In primary microglial cultures, genetic deletion or pharmacological inhibition of sEH by AUDA reduced thrombin- and hemin-induced microglial activation. Furthermore, AUDA reduced thrombin- and hemin-induced P38 MAPK and NF-κB activation in BV2 microglia cultures. Ultimately, AUDA attenuated N2A neuronal death that was induced by BV2 microglial conditioned media. CONCLUSIONS: Our results suggest that inhibition of sEH may provide a potential therapy for ICH by suppressing microglia/macrophage-mediated neuroinflammation.

Treatment with TO901317, a synthetic liver X receptor agonist, reduces brain damage and attenuates neuroinflammation in experimental intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) induces a series of inflammatory processes that contribute to neuronal damage and neurological deterioration. Liver X receptors (LXRs) are nuclear receptors that negatively regulate transcriptional processes involved in inflammatory responses, but their role in the pathology following ICH remains unclear. The present study investigated the neuroprotective effects and anti-inflammatory actions of TO901317, a synthetic LXR agonist, in a model of collagenase-induced ICH and in microglial cultures. METHODS: Mice subjected to collagenase-induced ICH injury were injected with either TO901317 (30 mg/kg) or vehicle 10 min after ICH and subsequently daily for 2 days. Behavioral studies, histology analysis, and assessments of hematoma volumes, brain water content, and blood-brain barrier (BBB) permeability were performed. The protein expression of LXR-α, LXR-ß, ATP binding cassette transporter-1 (ABCA-1), and inflammatory molecules was analyzed. The anti-inflammatory mechanism of TO901317 was investigated in cultured microglia that were stimulated with either lipopolysaccharide (LPS) or thrombin. RESULTS: ICH induced an increase in LXR-α protein levels in the hemorrhagic hemisphere at 6 h whereas LXR-ß expression remained unaffected. Both LXR-α and LXR-ß were expressed in neurons and microglia in the peri-ICH region and but rarely in astrocytes. TO901317 significantly attenuated functional deficits and brain damage up to 28 days post-ICH. TO901317 also reduced neuronal death, BBB disruption, and brain edema at day 4 post-ICH. These changes were associated with marked reductions in microglial activation, neutrophil infiltration, and expression levels of inflammatory mediators at 4 and 7 days. However, TO901317 had no effect on matrix metalloproteinase-9 activity. In BV2 microglial cultures, TO901317 attenuated LPS- and thrombin-stimulated nitric oxide production and reduced LPS-induced p38, JNK, MAPK, and nuclear factor-kappa B (NF-κB) signaling. Moreover, delaying administration of TO901317 to 3 h post-ICH reduced brain tissue damage and neuronal death. CONCLUSIONS: Our results suggest that enhancing LXR activation may provide a potential therapy for ICH by modulating the cytotoxic functions of microglia.

Transient receptor potential vanilloid 1 inhibition reduces brain damage by suppressing neuronal apoptosis after intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) induces a complex sequence of apoptotic cascades and inflammatory responses, leading to neurological impairment. Transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel with high calcium permeability, has been implicated in neuronal apoptosis and inflammatory responses. This study used a mouse ICH model and neuronal cultures to examine whether TRPV1 activation exacerbates brain damage and neurological deficits by promoting neuronal apoptosis and neuroinflammation. ICH was induced by injecting collagenase in both wild-type (WT) C57BL/6 mice and TRPV1-/- mice. Capsaicin (CAP; a TRPV1 agonist) or capsazepine (a TRPV1 antagonist) was administered by intracerebroventricular injection 30 min before ICH induction in WT mice. The effects of genetic deletion or pharmacological inhibition of TRPV1 using CAP or capsazepine on motor deficits, histological damage, apoptotic responses, blood-brain barrier (BBB) permeability, and neuroinflammatory reactions were explored. The antiapoptotic mechanisms and calcium influx induced by TRPV1 inactivation were investigated in cultured hemin-stimulated neurons. TRPV1 expression was upregulated in the hemorrhagic brain, and TRPV1 was expressed in neurons, microglia, and astrocytes after ICH. Genetic deletion of TRPV1 significantly attenuated motor deficits and brain atrophy for up to 28 days. Deletion of TRPV1 also reduced brain damage, neurodegeneration, microglial activation, cytokine expression, and cell apoptosis at 1 day post-ICH. Similarly, the administration of CAP ameliorated brain damage, neurodegeneration, brain edema, BBB permeability, and cytokine expression at 1 day post-ICH. In primary neuronal cultures, pharmacological inactivation of TRPV1 by CAP attenuated neuronal vulnerability to hemin-induced injury, suppressed apoptosis, and preserved mitochondrial integrity in vitro. Mechanistically, CAP reduced hemin-stimulated calcium influx and prevented the phosphorylation of CaMKII in cultured neurons, which was associated with reduced activation of P38 and c-Jun NH2 -terminal kinase mitogen-activated protein kinase signaling. Our results suggest that TRPV1 inhibition may be a potential therapy for ICH by suppressing mitochondria-related neuronal apoptosis.

Caveolin-1 deletion reduces early brain injury after experimental intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a subtype of stroke with high rates of morbidity and mortality. Caveolin-1 (Cav-1) is the main structural protein of caveolae and is involved in regulating signal transduction and cholesterol trafficking in cells. Although a recent study suggests a protective role of Cav-1 in cerebral ischemia, its function in ICH remains unknown. In this study, we examined the role of Cav-1 and in a model of collagenase-induced ICH and in neuronal cultures. Our results indicate that Cav-1 was up-regulated in the perihematomal area predominantly in endothelial cells. Cav-1 knockout mice had smaller injury volumes, milder neurologic deficits, less brain edema, and neuronal death 1 day after ICH than wild-type mice. The protective mechanism in Cav-1 knockout mice was associated with marked reduction in leukocyte infiltration, decreased expression of inflammatory mediators, including macrophage inflammatory protein (MIP)-2 and cyclooxygenase (COX)-2, and reduced matrix metalloproteinase-9 activity. Deletion of Cav-1 also suppressed heme oxygenase-1 expression and attenuated reactive oxygen species production after ICH. Moreover, deletion or knockdown of Cav-1 decreased neuronal vulnerability to hemin-induced toxicity and reduced heme oxygenase (HO)-1 induction in vitro. These data suggest that Cav-1 plays a deleterious role in early brain injury after ICH. Inhibition of Cav-1 may provide a novel therapeutic approach for the treatment of hemorrhagic stroke.

Superior gait performance and balance ability in Latin dancers.

Background: Latin dance consists of various fast and stability-challenging movements that require constant body adjustments to maintain proper posture and balance. Although human gaits are assumed to be symmetrical, several factors can contribute to asymmetrical behavior of the lower extremities in healthy adults. These include lower limb dominance, ground reaction forces, lower limb muscle power, foot placement angle, and range of joint motion. Gait impairment can lead to a high risk of falling, diminished mobility, and even cognition impairment. We hypothesized that Latin dancers might have a more symmetric gait pattern and better balance ability than healthy non-dancer controls. Methods: We investigated the impact of Latin dance training on gait behaviors and body balance. We recruited twenty Latin dancers and 22 normal healthy subjects to conduct walking experiments and one-leg stance tests, and we measured their kinematic data by inertial measurement units. We then defined four performance indexes to assess gait performance and body stability to quantify the potential advantages of dance training. Results: We found that the two gait asymmetric indexes during the walking test and the two performance indexes during the one-leg stance tests were better in Latin dancers compared with the healthy control group. The results confirmed the superiority of Latin dancers over the healthy control group in gait symmetry and balance stability. Our results suggest that Latin dancing training could effectively strengthen lower limb muscles and core muscle groups, thereby improving coordination and enhancing gait performance and balance. Conclusion: Latin dance training can benefit gait performance and body balance. Further studies are needed to investigate the effect of Latin dance training on gait and balance outcomes in healthy subjects and patients with gait disorders.

Differential Changes in Akt and AMPK Phosphorylation Regulating mTOR Activity in the Placentas of Pregnancies Complicated by Fetal Growth Restriction and Gestational Diabetes Mellitus With Large-For-Gestational Age Infants.

Background: Dysregulation of placental mechanistic target of rapamycin (mTOR) activity has been implicated in the pathophysiology of pregnancies complicated by idiopathic fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) with large-for-gestational-age (LGA) infants. However, the underlying mechanisms remain unclear. Methods: We obtained placentas from women with normal pregnancies (n = 11) and pregnancies complicated by FGR (n = 12) or GDM with LGA infants (n = 12) to compare the levels of total and phosphorylated forms of Akt, AMPK, TSC2, and mTOR among the three groups and used primary cytotrophoblast cells isolated from 30 normal term placentas to study the effects of oxygen-glucose deprivation (OGD) and increasing glucose concentrations on the changes of these factors in vitro. Results: Placentas from FGR pregnancies had lower phosphorylated Akt (p-Akt) levels (P < 0.05), higher p-AMPKα levels (P < 0.01), and lower mTOR phosphorylation (P < 0.05) compared to that of normal pregnant women. Conversely, women with GDM and LGA infants had higher p-Akt (P < 0.001), lower p-AMPKα (P < 0.05), and higher p-mTOR levels (P < 0.05) in the placentas than normal pregnant women. Furthermore, primary cytotrophoblast cells subjected to OGD had lower p-Akt and p-mTOR (both P < 0.05) and higher p-AMPKα levels (P < 0.05) than those cultured under standard conditions, but increasing glucose concentrations had opposite effects on the respective levels. Administering compound C, an AMPK inhibitor, did not significantly affect Akt phosphorylation but partially reversed mTOR phosphorylation. Administering LY294002, an Akt inhibitor, decreased p-mTOR levels, but did not change the levels of total and phosphorylated AMPKα. Conclusion: These results suggest that Akt and AMPK are involved in the regulation of trophoblast mTOR activity in the placentas of pregnancies complicated by FGR and GDM with LGA infants.

Risk factors for abnormal postpartum glycemic states in women diagnosed with gestational diabetes by the International Association of Diabetes and Pregnancy Study Groups criteria.

AIMS/INTRODUCTION: To evaluate the rate of postpartum glycemic screening tests (PGST) in women with gestational diabetes mellitus (GDM), and to investigate risk factors for abnormal PGST results. MATERIALS AND METHODS: We retrospectively analyzed the obstetric data of 1,648 women with GDM who gave birth after 28 completed weeks of gestation between 1 July 2011 and 31 December 2019 at Taipei Chang Gung Memorial Hospital, Taiwan. GDM was diagnosed by the International Association of Diabetes and Pregnancy Study Groups criteria. PGST was carried out at 6-12 weeks postpartum with a 75-g, 2-h oral glucose tolerance test, and the results were classified into normal, prediabetes and diabetes mellitus. Multiple logistic regression was used to assess the associations between various risk factors and abnormal PGST results. RESULTS: In total, 493 (29.9%) women underwent PGST and 162 (32.9%) had abnormal results, including 135 (27.4%) with prediabetes and 27 (5.5%) with diabetes mellitus. Significant risk factors for postpartum diabetes mellitus included insulin therapy during pregnancy (adjusted odds ratio [OR] 10.79, 95% confidence interval [CI] 4.07-28.58), birthweight >4,000 g (adjusted OR 10.22, 95% CI 1.74-59.89) and preterm birth <37 weeks' gestation (adjusted OR 3.33, 95% CI 1.09-10.22); whereas prepregnancy body mass index >24.9 kg/m2 (adjusted OR 1.99, 95% CI 1.24-3.21) was the major risk factor for postpartum prediabetes. CONCLUSIONS: Less than one-third of women with GDM underwent PGST, and nearly one-third of these women had abnormal results. Future efforts should focus on reducing the barriers to PGST in women with GDM.

Antenatal low-intensity pulsed ultrasound reduces neurobehavioral deficits and brain injury following dexamethasone-induced intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is a leading cause of perinatal mortality and morbidity, and IUGR survivors are at increased risk of neurodevelopmental deficits. No effective interventions are currently available to improve the structure and function of the IUGR brain before birth. This study investigated the protective effects of low-intensity pulsed ultrasound (LIPUS) on postnatal neurodevelopmental outcomes and brain injury using a rat model of IUGR induced by maternal exposure to dexamethasone (DEX). Pregnant rats were treated with DEX (200 µg/kg, s.c.) and LIPUS daily from gestational day (GD) 14 to 19. Behavioral assessments were performed on the IUGR offspring to examine neurological function. Neuropathology, levels of neurotrophic factors, and CaMKII-Akt-related molecules were assessed in the IUGR brain, and expression of glucose and amino acid transporters and neurotrophic factors were examined in the placenta. Maternal LIPUS treatment increased fetal weight, fetal liver weight, and placental weight following IUGR. LIPUS treatment also increased neuronal number and myelin protein expression in the IUGR brain, and attenuated neurodevelopmental deficits at postnatal day (PND) 18. However, the number of oligodendrocytes or microglia was not affected. These changes were associated with the upregulation of brain-derived neurotrophic factor (BDNF) and placental growth factor (PlGF) protein expression, and enhancement of neuronal CaMKII and Akt activation in the IUGR brain at PND 1. Additionally, LIPUS treatment promoted glucose transporter (GLUT) 1 production and BDNF expression in the placenta, but had no effects on GLUT3 or amino acid transporter expression. Our findings suggest that antenatal LIPUS treatment may reduce IUGR-induced brain injury via enhancing cerebral BDNF/CaMKII/Akt signaling. These data provide new evidence that LIPUS stimulation could be considered for antenatal neuroprotective therapy in IUGR.

Risk factors and adverse maternal and perinatal outcomes for women with dichorionic twin pregnancies complicated by gestational diabetes mellitus: A retrospective cross-sectional study.

AIMS/INTRODUCTION: The association between gestational diabetes mellitus (GDM) and adverse maternal and perinatal outcomes in twin pregnancies remains unclear. This study was undertaken to highlight risk factors for GDM in women with dichorionic (DC) twins, and to determine the association between GDM DC twins and adverse maternal and perinatal outcomes in a large homogeneous Taiwanese population. MATERIALS AND METHODS: A retrospective cross-sectional study was carried out on 645 women with DC twins, excluding pregnancies complicated by one or both fetuses with demise (n = 22) or congenital anomalies (n = 9), who gave birth after 28 complete gestational weeks between 1 January 2001 and 31 December 2018. Univariable and multiple logistic regression analyses were carried out. RESULTS: Maternal age >34 years (adjusted odds ratio 2.52; 95% confidence interval 1.25-5.07) and pre-pregnancy body mass index >24.9 kg/m2 (adjusted odds ratio 2.83, 95% confidence interval 1.47-5.46) were independent risk factors for GDM in women with DC twins. Newborns from women with GDM DC twins were more likely to be admitted to the neonatal intensive care unit (adjusted odds ratio 1.70, 95% confidence interval 1.06-2.72) than newborns from women with non-GDM DC twins. Other pregnancy and neonatal outcomes were similar between the two groups. CONCLUSIONS: Advanced maternal age and pre-pregnancy overweight or obesity are risk factors for GDM in women with DC twins. Except for a nearly twofold increased risk of neonatal intensive care unit admission of newborns, the pregnancy and neonatal outcomes for women with GDM DC twins are similar to those for women with non-GDM DC twins.

The effects of Ai Chi for balance in individuals with chronic stroke: a randomized controlled trial.

This study investigated the effectiveness of Ai Chi compared to conventional water-based exercise on balance performance in individuals with chronic stroke. A total of 20 individuals with chronic stroke were randomly allocated to receive either Ai Chi or conventional water-based exercise for 60 min/time, 3 times/week, and a total of 6 weeks. Balance performance assessed by limit of stability (LOS) test and Berg balance scale (BBS). Fugl-Meyer assessment (FMA) and gait performance were documented for lower extremity movement control and walking ability, respectively. Excursion and movement velocity in LOS test was significantly increased in anteroposterior axis after receiving Ai Chi (p = 0.005 for excursion, p = 0.013 for velocity) but not conventional water-based exercise. In particular, the improvement of endpoint excursion in the Ai Chi group has significant inter-group difference (p = 0.001). Both groups showed significant improvement in BBS and FMA yet the Ai Chi group demonstrated significantly better results than control group (p = 0.025). Ai Chi is feasible for balance training in stroke, and is able to improve weight shifting in anteroposterior axis, functional balance, and lower extremity control as compared to conventional water-based exercise.

Decreased placental apoptosis and autophagy in pregnancies complicated by gestational diabetes with large-for-gestational age fetuses.

INTRODUCTION: Dysregulation of placental apoptosis and autophagy are observed in pregnancy complications including preeclampsia and fetal growth restriction. However, studies of their changes in the placentas of women with gestational diabetes mellitus (GDM) show inconsistent results. We aimed to compare the changes in apoptosis, autophagy, and Bcl-2 family proteins in the placentas from women with normal pregnancies and those with GDM, with or without large-for-gestational age (LGA) infants and to investigate the effect of hyperglycemia on the changes in apoptosis, autophagy, and Bcl-2 family proteins in primary cytotrophoblastic cells. METHODS: Villous tissues were obtained from normal pregnant women and those with GDM, with or without LGA infants. Primary cytotrophoblast cells were isolated from normal term placentas and cultured under standard, hyperglycemic, or hyperosmotic conditions. RESULTS: Compared to placentas from normal pregnant women, those from GDM women with LGA infants were heavier, had lower beclin-1 and DRAM levels, less M30 and cleaved PARP immunoreactivity, and increased Ki-67 immunoreactivity. These changes were associated with increased Bcl-xL and decreased Bak levels. Increased glucose concentration led to lower ATG5, beclin-1, LC3B-II, p62, and DRAM levels, lower annexin V and M30-positive cell percentages, and less cleaved PARP changes compared with standard culture conditions. Hyperglycemia caused higher Bcl-xL levels and lower Bak and Bad levels than did standard culture conditions. DISCUSSION: There were differential changes in apoptosis and autophagy between placentas from normal pregnant women and those from GDM women with LGA infants. Bcl-2 family proteins are likely involved in the regulation of these changes.

Soluble epoxide hydrolase in the human placenta throughout gestation.

OBJECTIVE: To investigate the spatial and temporal changes of soluble epoxide hydrolase (sEH) in the human placenta throughout gestation and to study the effects of hypoxia-reoxygenation (HR) on the expression of sEH in villous explants in vitro. MATERIALS AND METHODS: Placental samples were obtained from women of different gestation and grouped as early (8-12 weeks, n = 10), mid- (16-28 weeks, n = 6), and late gestation (38-39 weeks, n = 10) according to gestational age. Immunohistochemistry, western blot, and real-time quantitative PCR were used to assess the cellular distribution and temporal changes of sEH. Villous explant cultures were used to study the effect of HR (8 h at 2% oxygen, followed by 16 h at 8% oxygen, two cycles) on the expression of sEH. RESULTS: Using a mouse monoclonal antibody against human sEH, immunoreactivity of sEH was observed mainly localized in the cytotrophoblasts and, to a lesser extent, the syncytiotrophoblast in the villous tissues throughout gestation. Compared to villous tissues of early gestation, the levels of sEH mRNA and protein were significantly increased in villous samples of mid- and late gestation. Furthermore, villous explants subjected to HR had significantly higher levels of sEH mRNA and protein compared to villous tissues kept at 8% oxygen throughout the experiment. CONCLUSION: Our results indicate that sEH is likely to play an essential role in the development of human placenta and HR is a possible factor regulating the expression of sEH in the placenta.

Risk of abnormal fetal growth in women with early- and late-onset preeclampsia.

OBJECTIVES: To investigate the risks of delivering small-for-gestational-age (SGA) and large-for-gestational-age (LGA) infants in women with early- (delivered before 34weeks of gestation) and late-onset (delivered at or after 34weeks of gestation) preeclampsia. STUDY DESIGN: We conducted a retrospective cohort study of 29,494 singleton deliveries after 24weeks' gestation, excluding pregnancies complicated by fetal anomalies, stillbirths, and prepregnancy diabetes mellitus. Univariate and multivariate logistic analyses adjusted for potential confounding factors, including prepregnancy body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM), were performed. RESULTS: Among women who delivered before 34weeks, significantly more women with preeclampsia delivered SGA infants than women without preeclampsia (50.6% vs. 7.0%; adjusted odds ratio [OR] 16.3; 95% confidence interval [CI] 8.1-32.9). Among women who delivered at or after 34weeks, women with preeclampsia had higher rates of delivering SGA (25.5% vs. 7.0%) and LGA (13.7% vs. 9.9%) infants than women without preeclampsia. After adjustment for confounding factors, preeclampsia remained a significant risk factor for delivering SGA infants (adjusted OR 5.7; 95% CI 4.6-7.1), but the association between preeclampsia and the delivery of LGA infants was diminished (adjusted OR 0.8; 95% CI 0.6-1.1). CONCLUSIONS: Our results confirm that preeclampsia is associated with SGA and that the association is stronger with early-onset disease. Although women with late-onset preeclampsia had a higher rate of delivering LGA infants, the association between late-onset preeclampsia and LGA is due to confounding factors, such as high prepregnancy BMI, excessive GWG, and GDM, related to maternal metabolic abnormalities.