Echinacoside, an active compound in the herb Herba Cistanche, has been reported to inhibit glutamate release. In this study, we investigated the effects of echinacoside on spontaneous excitatory synaptic transmission changes induced by 4-aminopyridine (4-AP), by using the in vitro rat hippocampal slice technique and whole-cell patch clamp recordings from CA3 pyramidal neurons. Perfusion with echinacoside significantly suppressed the 4-AP-induced epileptiform activity in a concentration-dependent manner. Echinacoside reduced 4-AP-induced increase in frequency of spontaneous excitatory postsynaptic currents (sEPSCs) but it did not affect the amplitude of sEPSCs or glutamate-activated currents, implicating a presynaptic mechanism of action. Echinacoside also potently blocked sustained repetitive firing, which is a basic mechanism of antiepileptic drugs. These results suggest that echinacoside exerts an antiepileptic effect on hippocampal CA3 pyramidal neurons by simultaneously decreasing glutamate release and blocking abnormal firing synchronization. Accordingly, our study provides experimental evidence that echinacoside may represent an effective pharmacological agent for treating epilepsy.
4-Aminopyridine ; Animals ; Anticonvulsants ; Cistanche* ; Epilepsy ; Excitatory Postsynaptic Potentials ; Fires ; Glutamic Acid ; Hippocampus ; In Vitro Techniques ; Perfusion ; Pyramidal Cells* ; Rats ; Synaptic Transmission

OBJECTIVES: The objectives of the research study were to determine ethical guidelines and principles applicable in the practice and research of eHealth and telehealth in the Philippines, how these are applicable to the Philippines, and to differentiate between the ethical issues in research and in clinical practice of eHealth.

METHODS: This research study used: 1) review of ethics manuscripts, guidelines and literature; 2) focused group discussion and key informant interviews of experts; and 3) triangulation. The information sought for the review were- 1) relevant policies, guidelines in eHealth that are pertinent to the discussion of eHealth ethics in the Philippines; 2) components of ethics in eHealth research; and 3) components of ethics in eHealth practice. The framework of the consultation with experts was to identify mechanisms and strategies in incorporating ethics in both eHealthpractice and eHealth research within the following- 1) in reference to existing laws, policies, and guidelines on ethics in medicine and health; and 2) in the context of the Philippine setting.

RESULTS: Based on the review, there are pertinent codes of ethics, applicable laws, policies and guidelines in eHealth, both in the international and local settings. The focus group discussion and key informant interview with experts yielded significant and deeper understanding on how to address the gaps and lapses of ethics applied to eHealth in the country. These recommendations were given which distinguish between the ethics in clinical practice and ethics in the planning and implementation of eHealth systems. There is also a need to resolve the problem of whose primary responsibility the patient is- the referring, commonly referred to as the attending physician in the local community, or the specialist from the center. The proposed resolution was also presented.

CONCLUSION: The study has shown how important eHealth in potentially promoting timely and improved health care access. However, there are still lapses and gaps in the implementation of policies and guidelines on and relating to eHealth in the Philippines as shown by the data culled from the review and the focus group discussions with the experts. With more specific ethical guidelines and relevant policies, the development and practice of eHealth and telehealth will be on its way in bridging the gap and aiding in health systems development in the Philippines, especially with the support of the national government and collaboration of various agencies and stakeholders.

Human ; Federal Government ; Focus Groups ; Codes Of Ethics ; Philippines ; Telemedicine ; Delivery Of Health Care ; Referral And Consultation

OBJECTIVETo introduce the Ages and Stages Questionnaires, Third Edition (ASQ-3), to China, created ASQ-Chinese (ASQ-C) and carried out studies of its national norm and the psychometrical properties in the children aged 1-66 months in the mainland of China in collaboration with the author of the ASQ System and under the authorizations from its publisher on translation, researches, publication and distribution of the ASQ-3.

METHODThe ASQ-3 questionnaires were translated and adapted into a Simplified Chinese version, the ASQ-C, with six steps such as translation, back-translation and adaptation and so on to ensure consistency with the core of the original document and to have the cultural relevance in China.A stratified cluster sampling method was utilized to recruit children aged 1-66 months with respect to demographic characteristics such as the proportion of population in each administrative region and in urban and rural areas and so on that are representative of 2010 China census data.A sample size of over 200 was collected for each ASQ-C age interval.Children were excluded from the normative sample who (1) are from communities or villages at an elevation of 2 000 m or above and(or) where simplified Chinese is not the official language, or (2) had been diagnosed as having a developmental delay by any authoritative organizations.The national normative sample for the ASQ-C had a total sample size of 4 452, sample size within each age interval ranged from 218 to 227, including 2 230 male cases and 2 222 female cases, 2 236 urban cases and 2 216 rural cases.A convenience sample was recruited from the normative sample to examine inter-rater reliability and test-retest reliability in all six administrative regions.Researchers completed the ASQ-C on the same child with their parents for 162 children for inter-rater reliability(the size of each ASQ-C age interval was 5-9); parents of 168 children completed another age-appropriate ASQ-C for test-retest reliability during 10-15 days after they completed the normative ASQ-C(The size of each ASQ-C age interval is 6-10). Another convenience sample was recruited from the follow-up of low birth weight infants for the concurrent validity of the ASQ-C in comparison with the Beijing Gesell.Parents of 198 children completed age-appropriate ASQ-C and professional administered to the children with the Beijing Gesell.In the ASQ-C norm and test-retest reliability, parents completed the age-appropriate ASQ-C, independently or with needed assistance. In inter-rater reliability, researchers completed the same ASQ-C after parents. In validity test, after parents completing age-appropriate ASQ-C, professional tested children with the Beijing Gesell.Data were analyzed using SPSS version 13.0 software.The mean and standard deviation of the national normative sample were calculated, reliability and validity of the ASQ-C was examined.

RESULTThe demographic characteristics of this Chinese sample match the 2010 China census data on gender, urban or rural location, and family income.All 20 intervals of the ASQ-C were standardized on 21 national normative samples.Cronbach's alpha coefficient for the whole measure was 0.8.The Pearson correlation coefficient between the ASQ-C total scores of the two raters was 0.8.The Pearson correlation coefficient between the ASQ-C total scores of the two times was 0.8 (all P<0.000 1). The sensitivity of ASQ-C was 87.50% and the specificity of ASQ-C was 84.48%.The percentage of the agreement between the ASQ-C and the Beijing Gesell was 84.74%.

CONCLUSIONThese findings indicate that the ASQ-C is a reliable and valid measure with a representative national sample aged 1-66 months.It can be used to screen and monitor the development of children in the mainland of China.

Beijing ; Child Development ; Child, Preschool ; China ; Female ; Humans ; Infant ; Infant, Low Birth Weight ; Language ; Male ; Parents ; Psychometrics ; Reproducibility of Results ; Sensitivity and Specificity ; Surveys and Questionnaires

Chronic constipation (CC) may impact on quality of life. There is substantial patient dissatisfaction; possible reasons are failure to recognize underlying constipation, inappropriate dietary advice and inadequate treatment. The aim of these practical guidelines intended for primary care physicians, and which are based on Asian perspectives, is to provide an approach to CC that is relevant to the existing health-care infrastructure. Physicians should not rely on infrequent bowel movements to diagnose CC as many patients have one or more bowel movement a day. More commonly, patients present with hard stool, straining, incomplete feeling, bloating and other dyspeptic symptoms. Physicians should consider CC in these situations and when patients are found to use laxative containing supplements. In the absence of alarm features physicians may start with a 2-4 week therapeutic trial of available pharmacological agents including osmotic, stimulant and enterokinetic agents. Where safe to do so, physicians should consider regular (as opposed to on demand dosing), combination treatment and continuous treatment for at least 4 weeks. If patients do not achieve satisfactory response, they should be referred to tertiary centers for physiological evaluation of colonic transit and pelvic floor function. Surgical referral is a last resort, which should be considered only after a thorough physiological and psychological evaluation.
Asia ; Asian Continental Ancestry Group ; Colon ; Constipation ; Health Resorts ; Humans ; Pelvic Floor ; Physicians, Primary Care ; Primary Health Care ; Quality of Life ; Referral and Consultation ; Sprains and Strains

Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.
Male ; Humans ; Androgens/therapeutic use* ; Receptors, Androgen/genetics* ; Prognosis ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Cell Line, Tumor ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Gene Expression Regulation, Neoplastic

Therapeutic plasma exchange (TPE) has been reported as a possible treatment for osmotic demyelination syndrome – central pontine myelinolysis (ODS-CPM), a degeneration of myelin within the central nervous system related to rapid hyponatremia correction, which though uncommon, has significant morbidity, and has no established specific treatment. We present our experience with a 41-year-old male with chronic kidney disease, maintained on steroids, who presented with lethargy and behavioral changes. Initial metabolic panel showed severe hyponatremia (Na 109 mEq/L). Despite cautious sodium correction, the patient’s sensorium decreased further and was intubated. Involuntary movements of the left face and arm were later seen. T2/FLAIR hyperintensities in the brainstem and thalami affirmed the diagnosis of ODS. A total of nine cycles (one cycle every two to three days) of TPE were completed. The patient was discharged with improved sensorium, from E2VxM4 to E4VxM6, and with no indication for hemodialysis due to improved creatinine. One year later, the patient has no remaining neurologic deficits. Our experience supports other case reports that TPE is a viable therapy for ODS-CPM.
Myelinolysis, Central Pontine ; Renal Insufficiency, Chronic

Axonal transport of mitochondria is critical for neuronal survival and function. Automatically quantifying and analyzing mitochondrial movement in a large quantity remain challenging. Here, we report an efficient method for imaging and quantifying axonal mitochondrial transport using microfluidic-chamber-cultured neurons together with a newly developed analysis package named "MitoQuant". This tool-kit consists of an automated program for tracking mitochondrial movement inside live neuronal axons and a transient-velocity analysis program for analyzing dynamic movement patterns of mitochondria. Using this method, we examined axonal mitochondrial movement both in cultured mammalian neurons and in motor neuron axons of Drosophila in vivo. In 3 different paradigms (temperature changes, drug treatment and genetic manipulation) that affect mitochondria, we have shown that this new method is highly efficient and sensitive for detecting changes in mitochondrial movement. The method significantly enhanced our ability to quantitatively analyze axonal mitochondrial movement and allowed us to detect dynamic changes in axonal mitochondrial transport that were not detected by traditional kymographic analyses.
Animals ; Axonal Transport ; physiology ; Cerebral Cortex ; cytology ; metabolism ; Drosophila melanogaster ; cytology ; metabolism ; Embryo, Mammalian ; Gene Expression ; Lab-On-A-Chip Devices ; Microscopy, Confocal ; Mitochondria ; metabolism ; ultrastructure ; Motor Neurons ; metabolism ; ultrastructure ; Movement ; Mutation ; Primary Cell Culture ; RNA-Binding Protein FUS ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Software