Unraveling the Photophysical Characteristics, Aromaticity, and Stability of π-Extended Acene-Quinodimethyl Thioamides†.

Poly-aromatic systems that contain quinodimethyl (QDM) units are appealing for several photonic and spintronic applications owing to the unique electronic structure, aromaticity, and spin state(s) of the QDM ring. Herein, we report the synthesis and characterization of novel QDM-based chromophores 1-3, which exhibit unique photo-excited behavior and aromaticity. Extending the aromatic core with a biphenyl/phenanthryl- and a pyrrolo-fragment led to reducing the optoelectronic bandgap and modulating the photophysics QDM 1-3. Yet, QDM 2 and 3 suffer from "aromaticity imbalance" and become relatively unstable compared to the parent compound QDM 1. Further assessment of local aromaticity using computational tools revealed that the pseudo-quinoidal ring B is the main driving force allowing to easily populate the excited triplet state of these chromophores. The present study provides complementary guidelines for designing novel non-classical poly-aromatic systems.

Current utilization and influencing factors of complementary and alternative medicine among children with neuropsychiatric disease: a cross-sectional survey in Korea.

BACKGROUND: Complementary and alternative medicine (CAM) is widespread but has various utilization rates according to country and the condition of patients. Generally, CAM is more frequently used in diseases that have no clear treatment method in conventional medicine. Therefore, a high utilization rate of CAM can be assumed in pediatric neurological diseases, but few studies have investigated the utilization of CAM in children with neuropsychiatric diseases. In particular, studies regarding the current use of CAM are scarce. METHODS: We conducted a survey of the parents or caregivers of patients who visited the pediatric rehabilitation clinic, pediatric neurology clinic, or pediatric psychiatry clinic at one university hospital from April to July 2011. We analyzed the factors that affect the utilization of CAM and other rehabilitation therapies. RESULTS: Among the 578 patients recruited, 258 patients have ever received CAM (51.5%), and the current CAM utilization rate was 19.0% (110 patients). Two hundred patients (34.6%) were currently receiving only other rehabilitation therapies, and 268 patients (46.4%) were currently receiving no type of therapy. The rate of current CAM usage was significantly high in epilepsy patients. The ORs of 1-6-year-old and 7-12-year-old children compared with 13-19-year-old children were 3.14 (95 % CI 1.31-7.53) and 3.34 (95% CI 1.64-6.79), respectively, and the OR of the group with longer disease duration (≥48 months) compared with the group with shorter disease duration was 3.36 (95% CI 1.71-6.59). Only the age and disease duration showed statistically significant differences between the patients who were administered CAM and those who received other rehabilitation therapies (p < 0.0001). CONCLUSIONS: CAM is preferred by patients under 13 years of age compared with patients aged 13-19 years, whereas other rehabilitation therapies are preferred by patients aged 1-6 years, followed by those aged 6-12 years and then by those aged 13-19 years. The patient's age and disease duration are the major factors influencing CAM use. Future studies should specify particular diseases, rather than combining all types of neuropsychiatric diseases, and include the socio-economic status of the parents.

Protocol for a prospective observational study of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy.

BACKGROUND: Cerebral palsy leads to many complications as well as delayed motor development, and early intensive rehabilitation in infancy, which is based on the theory of brain plasticity, is emphasized. In addition to conventional treatment, including physical, occupational, or speech-language therapies, children also have a demand for traditional Korean medicine interventions such as acupuncture or herbal medicine; however, a lack of evidence has made traditional Korean medicine difficult to implement in practice. We planned a multicentre, prospective, observational study to assess the effectiveness, safety and cost-effectiveness of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy. METHODS/DESIGN: Three hundred children with cerebral palsy aged 6 to 78 months will be recruited from six institutions. Data from each child are collected every month for a one-year period, during which time treatment might be changed or discontinued. A qualified investigator visits the sites to measure effectiveness variables, including Gross Motor Function Measure and Paediatric Evaluation of Disability Inventory. Adverse events and cost-effectiveness variables are collected using surveys conducted at baseline, mid-study, and end of study, as well as monthly tracking surveys. In the analyses, participants will be classified into two groups: group A children will be the conventional treatment group with physical, occupational, speech-language or other conventional rehabilitation therapies, whereas group B children will be the combination treatment group with traditional Korean medicine interventions, that is, herbal medicine, chuna, moxibustion and acupuncture, in addition to conventional treatment. DISCUSSION: Only a few clinical case reports have evaluated the effectiveness and safety of traditional Korean medicine; therefore, more data are required to provide optimal information to children with cerebral palsy and their guardians. We hypothesized that traditional Korean medicine combination treatment for children with cerebral palsy would have benefits compared with conventional therapy alone. The findings of this study might provide informative data for conducting economic evaluations and developing clinical research on combination treatment for cerebral palsy in South Korea. TRIAL REGISTRATION: NCT02223741.

A study of the development of the Korean version of PedsQL(TM) 3.0 cerebral palsy module and reliability and validity.

[Purpose] The purpose of this study was to develop the Korean version of the PedsQL(TM) 3.0 Cerebral Palsy Module to evaluate the health-related quality of life of children with cerebral palsy and to test the reliability and validity. [Subjects and Methods] The study included 108 caregivers of children with cerebral palsy aged 2 to 4 years and 72 caregivers of children aged 5 to 7 years, who visited multiple sites between February and August 2015. The Translation Commission performed the first translation with the approval of the Mapi Research Trust Company to create a Korean-version of the PedsQL(TM). Afterwards, back-translation was performed by one translator specializing in health and medical treatment who was a native English-speaker fluent in Korean, and one native Korean-speaker fluent in English. The consistency of each question was confirmed and a translation-integrated version was created. Test components were explained to caregivers during a one-on-one interview; caregivers then completed the PedsQL(TM) questionnaire and a Pediatric Evaluation Disability Inventory (PEDI) questionnaire. Subjects contributing to test-retest measures were asked to repeat the PedsQL questionnaire one week later and return it by mail. To assess data quality for the survey question results, non-response rate, ceiling effect, and floor effect were analyzed. Test-retest reliability and internal consistency reliability were assessed. For test-retest reliability, an intraclass correlation coefficient (ICC) was calculated, and for internal consistency reliability, Cronbach's alpha was used. To test criterion-related validity, Pearson's correlation coefficient was used. [Results] The content validity of the PedsQL 3.0 Cerebral Palsy Module was high for both age groups, and demonstrated significant internal consistency (>0.7) in all areas. For test-retest reliability, both groups demonstrated a significant ICC (>0.61). Correlation with the PEDI was statistically significant in all areas except pain and hurt. [Conclusion] The Korean version of the PedsQL(TM) 3.0 Cerebral Palsy Module was found to be reliable and valid, and is expected to contribute greatly to the evaluation of the quality of life of children with cerebral palsy.

Effects of Korean red ginseng on T-cell repopulation after autologous hematopoietic stem cell transplantation in childhood cancer patients.

Background: Although the survival outcomes of childhood cancer patients have improved, childhood cancer survivors suffer from various degrees of immune dysfunction or delayed immune reconstitution. This study aimed to investigate the effect of Korean Red Ginseng (KRG) on T cell recovery in childhood cancer patients who underwent autologous hematopoietic stem cell transplantation (ASCT) from the perspective of inflammatory and senescent phenotypes. Methods: This was a single-arm exploratory trial. The KRG group (n = 15) received KRG powder from month 1 to month 12 post-ASCT. We compared the results of the KRG group with those of the control group (n = 23). The proportions of T cell populations, senescent phenotypes, and cytokine production profiles were analyzed at 1, 3, 6, and 12 months post-ASCT using peripheral blood samples. Results: All patients in the KRG group completed the treatment without any safety issues and showed a comparable T cell repopulation pattern to that in the control group. In particular, KRG administration influenced the repopulation of CD4+ T cells via T cell expansion and differentiation into effector memory cell re-expressing CD45RA (EMRA) cells. Although the KRG group showed an increase in the number of CD4+ EMRA cells, the expression of senescent and exhausted markers in these cells decreased, and the capacity for senescence-related cytokine production in the senescent CD28- subset was ameliorated. Conclusions: These findings suggest that KRG promotes the repopulation of CD4+ EMRA T cells and regulates phenotypical and functional senescent changes after ASCT in pediatric patients with cancer.

Side-Chain Engineering in Hydrophilic n-Type π-Conjugated Polymers for Enhanced Reactivity.

Minor changes to side chains in conjugated polymers (CPs) can have pronounced effects on polymer properties by altering backbone planarity, solubility, and interaction with ions. Here, we report the photocontrolled synthesis of hydrophilic CPs from Grignard monomers and find that switching from alkyl to oligo(ethylene glycol) (OEG) side chains changes their photoreactivity. Specifically, installing hydrophilic side chains on the same monomer core yields higher molecular weight polymers and allows polymerization to proceed with lower-energy red light. Additionally, we discover a side chain decomposition pathway for N-OEG monomers, which are prevalent in CP research. Decomposition can be overcome by adding an extra methylene unit in the side chains without compromising polymer molecular weight or hydrophilicity. Importantly, this polymerization does not require transition metal catalysts and is a promising approach to the preparation of n-type conjugated block copolymers.

Photophysical Insights of Halogenated Dipyrrolonaphthyridine-Diones as Potential Photodynamic Therapy Agents†.

We report the synthesis and photophysical characterization of novel halogenated dipyrrolonaphthyridine-diones (X2 -DPNDs, X = Cl, Br, and I), as candidates for photodynamic therapy (PDT) application. Apart from the heavy atom-induced spin-orbit coupling (SOC) dynamics in the investigated X2 -DPNDs, it was found that the position of the halogen atom (relative to the nitrogen of the pyrrole ring) also influenced the triplet excited state behavior. Interestingly, the faster/efficiency sensitization of 3 O2 to 1 O2 using X2 -DPND correlates with the rate of triplet population, kISC >1.6 × 108 s-1 for I2 -DPND vs kISC >2.9 × 109 s-1 for Cl2 -DPND and Br2 -DPND (where τISC  = 343 ± 3 ps for I2 -DPND and τISC  = 5-6 ns for Cl2 -DPND and Br2 -DPND are the lowest time constants/values for ISC). Furthermore, the heavy atom-induced SOC in Cl2 -DPND and Br2 -DPND did not lead to a reduction of the corresponding fluorescence (ca 75% vs 67% for the parent DPND). The attractive photophysical characteristics of Cl2 /Br2 -DPND put them on the landscape as not only promising PDT agents but also as fluorescence probes. The present study is a stepping stone in the development of novel organic photosystems for synergistic photomedicinal applications.

Estimation of Singlet Oxygen Quantum Yield Using Novel Green-Absorbing Baird-type Aromatic Photosensitizers.

We report two new organic green-absorbing singlet oxygen (1 O2 ) photosensitizers: Quinoidal naphthyl thioamide (QDM) and bis-iodol-dipyrrolonaphthyridine-dione (I2 -DPND), with triplet energies of 40.8 and 47.5 kcal mol-1 (at 77 K in a glassy matrix) , respectively. The UV-vis absorption and emission characteristics of QDM and I2 -DPND are similar to other commercially available organic 1 O2 photosensitizers such as Rose Bengal, which was used as standard/reference to estimate the 1 O2 quantum yield (Φ∆ ) of the chromophores under study. Using 9,10-diphenylanthracene (DPA) as an 1 O2 quencher, we estimated the Φ∆ ≈ 67-85% for QDM and Φ∆ ≈ 25-32% for I2 -DPND. The discrepancy in the Φ∆ values could be explained by the apparent photo-decomposition of the later dye. Nevertheless, the high Φ∆ value for QDM is unprecedented, as this chromophore exhibits relatively low structural complexity and could further be derivatized to create novel photodynamic agents.

Integrative medicine rehabilitation for children with cerebral palsy: a study protocol for a multicenter pragmatic randomized controlled trial.

BACKGROUND: Traditional Korean medicine (TKM) has been employed for the treatment of children with cerebral palsy in Korea; however, the addition of TKM to usual rehabilitation (UR) treatment is hindered by insufficient evidence of clinical improvement with TKM in patients with cerebral palsy. In this study, we will evaluate the effectiveness and safety of integrative medicine rehabilitation (IMR) for cerebral palsy through a randomized controlled clinical study. METHODS: Eighty children (2-6 years old) diagnosed with cerebral palsy will be recruited and randomly divided into groups A and B. Patients in group A will receive IMR with UR, while those in group B will receive only UR during weeks 1-12 of the study. IMR includes acupuncture treatment (head and limb acupuncture) three times a week and the administration of herbal medicine (Yukgunza-tang and Yukmijihwang-tang extracts) twice a day in parallel with UR. Evaluations will be conducted at the beginning of the study and at 12 and 24 weeks (follow-up). The primary outcome is the Gross Motor Function Measure-88 score, and the secondary outcomes are the scores for the Goal Attainment Scale, Korean Bayley Scales of Infant Development III, and the Pediatric Quality of Life Inventory, and adverse events. DISCUSSION: This will be the first pragmatic randomized controlled trial to evaluate the efficacy and safety of IMR in children with cerebral palsy in Korea. The results will help to demonstrate if IMR is an effective therapeutic approach for cerebral palsy. TRIAL REGISTRATION: Ministry of Food and Drug Safety 31361 ( http://www.mfds.go.kr ). Registered on 29 June 2017. Clinical Research Information Service KCT0002620 ( https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=9819 ). Registered on 29 December 2017.

Electroacupuncture on the Scalp over the Motor Cortex Ameliorates Behavioral Deficits Following Neonatal Hypoxia-Ischemia in Rats via the Activation of Neural Stem Cells.

Electroacupuncture (EA) therapy via alternating current stimulation on the scalp over the motor cortex is used for the treatment of brain disorders. Perinatal hypoxia-ischemia (HI), a brain injury in newborns, leads to long-term neurologic complications. Here, we investigated whether EA could promote functional improvements and neurogenesis in a neonatal HI rat model. A neonatal HI rat model was induced by permanent ligation of the left carotid artery in postnatal day 7 pups. EA for neonatal HI rats was performed at 2 Hz (1, 3, or 5 mA; 20 min) from 4-6 weeks after birth. HI rats undergoing EA had improved motor and memory function, with the greatest improvement after 3 mA EA. The corpus callosum was significantly thicker and showed a significant increase in proliferating astrocytes in the 3 mA EA group. We observed proliferating cells and a greater number of newly developed neurons and astrocytes in the subventricular zone and dentate gyrus of the 3 mA EA group than in those of the HI group. These results suggest that EA promotes functional improvements following neonatal HI assault via the proliferation and differentiation of neural stem cells. This effect was the strongest after 3 mA EA, suggesting that this is the optimal treatment dose.

Moxibustion as an adjunct for lower urinary tract symptoms associated with benign prostate enlargement: A randomized controlled pilot trial.

BACKGROUND: Benign prostatic enlargement (BPE) causes discomfort in daily life, including lower urinary tract symptoms (LUTSs) caused by the enlarged prostate, and requires long-term management as a chronic, irreversible disease. To improve LUTS, certain complementary therapies have been used with or without doctors' directions. Conventional treatments and complementary therapies tend to be combined unsystematically, depending on patient preference; thus, research for safe and efficient combination therapy is warranted. METHODS: Twenty-nine participants were randomly assigned to an integrative group (IG, n = 15) or a conventional group (CG, n = 14). The IG received moxibustion (twice weekly for 4 weeks, at the acupuncture points SP6, LR3, and CV4) and conventional medication for 4 weeks, followed by conventional medication alone for 8 weeks. The CG received conventional medication alone for 12 weeks. The outcome measures were International Prostate Symptom Score (IPSS), patient's global impression of changes (PGIC), maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), and frequency-volume chart. RESULTS: Total IPSS (IG, -2.4 ±â€Š4.2; CG, 0.9 ±â€Š4.0; P = .039), PGIC-A (IG, 3.5 ±â€Š1.0; CG, 2.2 ±â€Š1.0; P = .001), and PGIC-B (IG, 3.5 ±â€Š0.1; CG, 4.7 ±â€Š0.6; P = .004) were significantly improved in the IG compared with the CG, 4 weeks after baseline. Among the IPSS items, incomplete emptying (IG, -0.6 ±â€Š0.7; CG, 0.4 ±â€Š1.2; P = .019), straining (IG, -0.6 ±â€Š0.8; CG, 0.2 ±â€Š1.2; P = .046), and nocturia (IG, -0.8 ±â€Š1.4; CG, 0.1 ±â€Š1.0; P = .045) showed significant differences. The Qmax and PVR volume did not differ significantly at 12 weeks after the baseline. CONCLUSION: Moxibustion can be considered an adjunct therapy to improve LUTS in BPE patients. A full-sized randomized controlled trial would be feasible with comparator modifications and an extended study period. The study design should include a placebo group and narrow the eligibility to subjects who do not respond well to conventional treatments.

Design, synthesis, and biological evaluation of novel imidazo[1,2-a]pyridinecarboxamides as potent anti-tuberculosis agents.

Tuberculosis (TB) is a highly infectious disease that has been plaguing the human race for centuries. The emergence of multidrug-resistant strains of TB has been detrimental to the fight against tuberculosis with very few safe therapeutic options available. As part of an ongoing effort to identify potent anti-tuberculosis agents, we synthesized and screened a series of novel imidazo[1,2-a]pyridinecarboxamide derivatives for their anti-tuberculosis properties. These compounds were designed based on reported anti-tuberculosis properties of the indolecarboxamides (I2Cs) and imidazo[1,2-a]pyridinecarboxamides (IPAs). In this series, we identified compounds 15 and 16 with excellent anti-TB activity against H37Rv strain of tuberculosis (MIC = 0.10-0.19 µM); these compounds were further screened against selected clinical isolates of Mtb. Compounds 15 and 16 showed excellent activities against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of TB (MIC range: 0.05-1.5 µM) with excellent selectivity indices. In addition, preliminary ADME studies on compound 16 showed favorable pharmacokinetic properties.

Weisheng-Tang Ameliorates Acute Ischemic Brain Damage in Mice by Maintaining Blood-Brain Barrier Integrity.

Stroke is one of the major causes of death and long-term disability worldwide; the associated breakdown of the blood-brain barrier (BBB) aggravates ischemic brain damage. Accordingly, many medicinal herbs and formulas have been used to treat stroke-related symptoms. In this study, we selected two Korean herbal medicine formulas, Weisheng-tang and Tongxuewan, through Dongeuibogam text-mining analysis, and evaluated their protective effect on BBB disruption and brain damage in stroke. Ischemic brain damage was induced in mice by photothrombotic cortical ischemia. The infarct volume, brain edema, neurological deficits, and motor function 24 h after ischemic injury were analyzed. We investigated BBB breakdown by measuring Evans blue extravasation in addition to endothelial cells, tight junction proteins, protease-activated receptor-1 (PAR-1), and matrix metalloproteinase-9 (MMP-9) using immunofluorescence staining and confocal microscopy. Pretreatment with Weisheng-tang significantly reduced infarct volume and edema and improved neurological and motor functions; however, Tongxuewan did not. In addition, Weisheng-tang decreased brain infarction and edema and recovered neurological and motor deficit in a dose-dependent manner (30, 100, and 300 mg/kg). Weisheng-tang pretreatment resulted in significantly less BBB damage and higher brain microvasculature after focal cerebral ischemia. Tight junction proteins, such as zonula occludens-1 (ZO-1) and claudin-5, were preserved in Weisheng-tang-pretreated mice. Moreover, the ischemic brain in these mice showed suppressed PAR-1 and MMP-9 expression. In conclusion, our findings show that Weisheng-tang, which was selected through literature analysis but has not previously been used as a stroke remedy, exerts protective effects against ischemic brain damage and suggest its possible application for potential stroke patients, especially in the elderly.

Effectiveness and safety of moxibustion for alleviating symptoms of overactive bladder: A prospective, randomized controlled, crossover-design, pilot study.

BACKGROUND: This study aimed to evaluate trial feasibility and explore the potential efficacy and safety of moxibustion in the treatment of overactive bladder (OAB). METHOD: A randomized, controlled, cross-over, assessor blinded design was used. This study was conducted in an outpatient department of a university hospital in Republic of Korea. The overall study period was 8 weeks. Participants were randomly allotted to either Group A or Group B. Group A participants underwent 8 to 12 sessions of moxibustion with behavioral training during the first 4 weeks, while the Group B participants received behavioral training only. Over the next 4 weeks, the treatment offered to the 2 groups was reversed (Group A participants received behavioral training only, while Group B participants underwent the moxibustion session with behavioral training). The OAB-validated 8-question awareness tool (OAB-V8), OAB symptom scores (OABSS), visual analog scale (VAS) for lower urinary tract symptoms, and frequency voiding chart were used to assess outcomes. For analysis, we used effect size, measured as Hedge's g, to present descriptive results indicating the actual difference between the groups. RESULTS: Compared to that in Group B, the Hedge's g of OAB-V8 for the former 4 weeks in Group A was -0.248, that of OABSS was -1.531, and that of VAS was -0.713. During the latter 4 weeks, Group B showed similar effect with g = 0.465, 1.207, and 0.427 for OAB-V8, OABSS, and VAS, respectively, compared to Group A. The portion of nocturnal voiding volume decreased (g = -0965), the mean voiding volume increased (g = 0.690), and the voiding frequency decreased (g = -0.498) with moxibustion. CONCLUSIONS: Moxibustion might be considered as an alternative for OAB. A full-sized randomized controlled trial may be feasible with minimal modification in outcome measures and comparator population. OTHER INFORMATION: This clinical trial has been registered on clinicaltrials.gov (NCT02271607).

A cross-sectional survey of clinical factors that influence the use of traditional Korean medicine among children with cerebral palsy.

BACKGROUND: Traditional Korean medicine (TKM) is widely used to treat children with cerebral palsy (CP) in Korea; however, studies investigating factors that influence the use of TKM are scarce. Thus, we investigated the clinical factors that might influence the use of TKM. METHODS: A population-based, cross-sectional, multicenter survey was performed from August 2014 to May 2016. The history of TKM use, type and severity of CP, current treatment characteristics, presence of accompanying disabilities or other health problems not directly related to CP, and monthly cost for the treatment of CP were surveyed. RESULTS: In total, 182 children were recruited, and 78 children (42.9%) had used TKM. Among these 78 children, 50 (64.1% of the TKM-use group) had used both acupuncture and herbal medication, 15 (19.2%) had used acupuncture only, and 13 (16.7%) had used herbal medication only. Children with non-typical CP, accompanying disabilities and general health problems tended to use TKM. The monthly cost of treatment for CP was significantly higher in the TKM-use group than that in the no-TKM-use group, suggesting that economically disadvantaged children may have difficulty in accessing TKM. Dietary supplements, conventional pharmacological treatments, and rehabilitation therapies did not affect TKM use. CONCLUSION: Children with non-typical symptoms or those with poor overall health status are likely to use TKM. Additionally, TKM use leads to increased treatment costs. Studies investigating the motivation for starting or ceasing TKM therapy, socioeconomic factors and the attitude of parents towards complementary and alternative medicine should be performed.

Combined therapy involving electroacupuncture and treadmill exercise attenuates demyelination in the corpus callosum by stimulating oligodendrogenesis in a rat model of neonatal hypoxia-ischemia.

We investigated whether electroacupuncture (EA) and treadmill (TM) exercise improve behaviors related to motor and memory dysfunction in a cerebral palsy-like rat model via activation of oligodendrogenesis. A neonatal hypoxia-ischemia model was created using Sprague-Dawley rats (P7), and these underwent EA stimulation and treadmill training from 3 to 5weeks after hypoxia-ischemia induction. EA treatment was delivered via electrical stimulation (2Hz, 1mA) at two acupoints, Baihui (GV20) and Zusanli (ST36). Behavioral tests showed that EA alleviated motor dysfunction caused by hypoxia-ischemia on a rotarod test, and TM exercise alleviated motor and memory dysfunction seen on cylinder and passive avoidance tests. Combined therapy with EA and TM exercise showed synergistic effects on the cylinder, rotarod, and catwalk tests. TM exercise significantly restored corpus callosum thickness, and combined therapy with EA and TM restored myelin basic protein (MBP) levels in this region. While EA stimulation only increased activation of cAMP-response element binging protein (CREB) in oligodendrocytes of the corpus callosum, TM exercise increased newly generated oligodendrocyte progenitor cells or oligodendrocytes via activation of CREB. Synergistic effects on oligodendrogenesis were also observed by the combined therapy. Furthermore, the combined therapy induced mature brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex. These results demonstrate that combined therapy with EA and TM exercise may restore myelin components following neonatal hypoxia-ischemia via upregulation of oligodendrogenesis involving CREB/BDNF signaling, which subsequently improves motor and memory function. Therefore, combined therapy with EA and TM exercise offers another treatment option for functional recovery from injuries caused by neonatal hypoxia-ischemia, such as cerebral palsy.

Combination of Constraint-Induced Movement Therapy with Electroacupuncture Improves Functional Recovery following Neonatal Hypoxic-Ischemic Brain Injury in Rats.

AIM: Neonatal hypoxic-ischemia (HI) due to insufficient oxygen supply and blood flow during the prenatal and postnatal periods can cause cerebral palsy, a serious developmental condition. The purpose of this study was to investigate the efficacy of combining constraint-induced movement therapy (CIMT) and electroacupuncture to treat rat neonatal HI brain injury. METHODS: The left common carotid arteries of postnatal day 7 rats were ligated to induce HI brain injury, and the neonates were kept in a hypoxia chamber containing 8% oxygen for 2 hrs. Electroacupuncture at Baihui (GV 20) and Zusanli (ST 36) was performed concurrently with CIMT 3 weeks after HI induction for 4 weeks. RESULTS: Motor asymmetry after HI was significantly improved in the CIMT and electroacupuncture combination group, but HI lesion size was not improved. The combination of CIMT and electroacupuncture after HI injury increases NeuN and decreases GFAP levels in the cerebral cortex, suggesting that this combination treatment inversely regulates neurons and astrocytes. In addition, the combination treatment group reduced the level of cleaved caspase-3, a crucial mediator of apoptosis, in the cortex. CONCLUSIONS: Our findings indicate that a combination of CIMT and electroacupuncture is an effective method to treat hemiplegia due to neonatal HI brain injury.

Comparative analysis of the beneficial effects of treadmill training and electroacupuncture in a rat model of neonatal hypoxia-ischemia.

In the present study, we investigated whether treadmill training and electroacupuncture (EA) have autonomous or synergistic beneficial effects on deficits caused by neonatal hypoxia­ischemia in Sprague-Dawley rats. For this purpose, rats subjected to hypoxia-ischemia underwent treadmill training and EA stimulation from 4 to 8 weeks of age. Conventional EA (CEA) and scalp EA (SEA) were delivered by electrical stimulation (2 Hz, 1 mA) at traditional acupoints and at the scalp to the primary motor area, respectively. In the behavioral examination, markedly improved performances in the rotarod test were observed in the rats that underwent treadmill exercise, and in the rats that underwent treadmill exercise and CEA compared to the untreated rats subjected to hypoxia-ischemia. An improvement was also observed in the passive avoidance test in the rats that underwent treadmill training and EA. As shown by western blot analysis, the expression levels of neuronal nuclei (NeuN), 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin basic protein (MBP) exhibited a significant decrease in the contralateral subventricular zone (SVZ) of the rats subjected to hypoxia­ischemia compared to the controls; however, these expression levels increased following treadmill exercise and EA stimulation. As shown by immunohistochemical analyses, the thickness of the corpus callosum and the integrated optical density (IOD) of MBP were significantly increased in the rats subjected to treadmill exercise and EA compared to the untreated rats subjected to hypoxiaa-ischemia. The synergistic effects of treadmill training and EA were also observed in the protein levels and IOD of MBP. A marked increase in the number of bromodeoxyuridine (BrdU)- and BrdU/NeuN-positive cells in the contralateral SVZ was also observed in the rats that underwent treadmill training and EA; the number of BrdU-positive cells was synergistically affected by treadmill training and EA. These results suggest that treadmill training and EA stimulation contribute to the enhancement of behavioral recovery following hypoxia-ischemia via the upregulation of myelin components and neurogenesis. Thus, treatment with EA stimulation, as well as treadmill training offers another treatment option to promote functional recovery in cerebral palsy.

Feasibility of UltraFast Doppler in Post-operative Evaluation of Hepatic Artery in Recipients following Liver Transplantation.

To determine the feasibility of using UltraFast Doppler in post-operative evaluation of the hepatic artery (HA) after liver transplantation (LT), we evaluated 283 simultaneous conventional and UltraFast Doppler sessions in 126 recipients over a 2-mo period after LT, using an Aixplorer scanner The Doppler indexes of the HA (peak systolic velocity [PSV], end-diastolic velocity [EDV], resistive index [RI] and systolic acceleration time [SAT]) by retrospective analysis of retrieved waves from UltraFast Doppler clips were compared with those obtained by conventional spectral Doppler. Correlation, performance in diagnosing the pathologic wave, examination time and reproducibility were evaluated. The PSV, EDV, RI and SAT of spectral and UltraFast Doppler measurements exhibited excellent correlation with favorable diagnostic performance. During the bedside examination, the mean time spent for UltraFast clip storing was significantly shorter than that for conventional Doppler US measurements. Both conventional and UltraFast Doppler exhibited good to excellent inter-analysis consistency. In conclusion, compared with conventional spectral Doppler, UltraFast Doppler values correlated excellently and yielded acceptable pathologic wave diagnostic performance with reduced examination time at the bedside and excellent reproducibility.