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author:("Xu, menglian")
1.  The mitochondrial division inhibitor Mdivi-1 rescues mammalian neurons from anesthetic-induced cytotoxicity 
Molecular Brain  2016;9:35.
Concerns have risen regarding the potential side effects of clinical exposure of the pediatric population to inhalational anesthetics, and how they might impact cognitive, learning, and memory functions. However, neither the mechanisms of anesthetic cytotoxicity, nor potential protective strategies, have yet been fully explored. In this study, we examined whether two of the most commonly used inhalational anesthetics, sevoflurane and desflurane, affect neuronal viability and synaptic network assembly between cultured rat cortical neurons.
Primary rat cortical neuron cultures were exposed to equipotent sevoflurane or desflurane for 1 hour. Neuron viability, synaptic protein expression, mitochondrial morphology, and neurite growth were assayed with immunostaining and confocal microscopy techniques. The effects of anesthetics on the functional development of neural networks were evaluated with whole-cell patch clamp recordings of spontaneous synaptic currents. Our results demonstrate that an acute exposure to sevoflurane and desflurane inhibits the development of neurite processes, impacts the mitochondria, and compromises synaptic proteins - concomitant with a reduction in synaptic function in mature networks. Interestingly, pretreatment of neurons with a mitochondrial division inhibitor (Mdivi-1) not only protected mitochondria integrity but also played a protective role against anesthetic-induced structural and functional neurotoxicity.
We show that Mdivi-1 likely plays a protective role against certain harmful effects of general anesthetics on primary rat neuronal cultures. In addition, Mdivi-1 alone plays a direct role in enhancing growth and modulating synaptic activity. This study highlights the importance of further study into possible protective agents against anesthetic neurotoxicity.
PMCID: PMC4806411  PMID: 27009068
General anesthetics; Neurotoxicity; Sevoflurane; Desflurane; Mitochondria; Synapse
2.  Australian national birthweight percentiles by sex and gestational age for twins, 2001–2010 
BMC Pediatrics  2015;15:148.
Birthweight remains one of the strongest predictors of perinatal mortality and disability. Birthweight percentiles form a reference that allows the detection of neonates at higher risk of neonatal and postneonatal morbidity. The aim of the study is to present updated national birthweight percentiles by gestational age for male and female twins born in Australia.
Population data were extracted from the Australian National Perinatal Data Collection for twins born in Australia between 2001 and 2010. A total of 43,833 women gave birth to 87,666 twins in Australia which were included in the study analysis. Implausible birthweights were excluded using Tukey’s methodology based on the interquartile range. Univariate analysis was used to examine the birthweight percentiles for liveborn twins born between 20 and 42 weeks gestation.
Birthweight percentiles by gestational age were calculated for 85,925 live births (43,153 males and 42,706 females). Of these infants, 53.6 % were born preterm (birth before 37 completed weeks of gestation) while 50.2 % were low birthweight (<2500 g) and 8.7 % were very low birthweight (<1500 g). The mean birthweight decreased from 2462 g in 2001 to 2440 g in 2010 for male twins, compared with 2485 g in 1991–94. For female twins, the mean birthweight decreased from 2375 g in 2001 to 2338 g in 2010, compared with 2382 g in 1991–94.
The birthweight percentiles provide clinicians and researchers with up-to-date population norms of birthweight percentiles for twins in Australia.
PMCID: PMC4599725  PMID: 26450410
Twins; Birth weight; Gestational age; Small for gestational age
3.  Gastrodin Suppresses the Amyloid β-Induced Increase of Spontaneous Discharge in the Entorhinal Cortex of Rats 
Neural Plasticity  2014;2014:320937.
Accumulated soluble amyloid beta- (Aβ-) induced aberrant neuronal network activity may directly contribute to cognitive deficits, which are the most outstanding characteristics of Alzheimer's disease (AD). The entorhinal cortex (EC) is one of the earliest affected brain regions in AD. Impairments of EC neurons are responsible for the cognitive deficits in AD. However, little effort has been made to investigate the effects of soluble Aβ on the discharge properties of EC neurons in vivo. The present study was designed to examine the effects of soluble Aβ1−42 on the discharge properties of EC neurons, using in vivo extracellular single unit recordings. The protective effects of gastrodin (GAS) were also investigated against Aβ1−42-induced alterations in EC neuronal activities. The results showed that the spontaneous discharge of EC neurons was increased by local application of soluble Aβ1−42 and that GAS can effectively reverse Aβ1−42-induced facilitation of spontaneous discharge in a concentration-dependent manner. Moreover, whole-cell patch clamp results indicated that the protective function of GAS on abnormal hyperexcitability may be partially mediated by its inhibitory action on Aβ1−42-elicited inward currents in EC neurons. Our study suggested that GAS may provide neuroprotective effects on Aβ1−42-induced hyperactivity in EC neurons of rats.
PMCID: PMC4251795  PMID: 25485157
4.  The increased trend in mothers’ hospital admissions for psychiatric disorders in the first year after birth between 2001 and 2010 in New South Wales, Australia 
BMC Women's Health  2014;14:119.
The burden of mental and behavioural disorders in Australia has increased significantly over the last decade. The aim of the current study is to describe the hospital admission rates for mental illness over a 10-year period for primiparous mothers in the first year after birth.
This is an Australian population-based descriptive study with linked data from the New South Wales Midwives Data Collection and Admitted Patients Data Collection. The study population included primiparous mothers who gave birth between 1 January 2001 and 31 December 2010. All hospital admissions with a mental health diagnosis in the first year after birth were recorded.
There were 6,140 mothers (1.67%) admitted to hospital with a principal diagnosis of mental health in the first year after birth between 2001 and 2010 in New South Wales (7,884 admissions, 2.15%). The hospital admission rates increased significantly over time, particularly from 2005. The increase in hospital admissions was mainly attributed to the diagnoses of unipolar depression, adjustment disorders and anxiety disorders.
This study shows that hospital admissions for mothers with a mental health diagnosis after birth in New South Wales has significantly increased in the last decade. Possible reasons for this change need to be studied further.
PMCID: PMC4261248  PMID: 25263987
Mental health; Increasing trend; Postpartum; Data linkage
5.  Mental and Behavioral Disorders Due to Substance Abuse and Perinatal Outcomes: A Study Based on Linked Population Data in New South Wales, Australia 
Background: The effects of mental and behavioral disorders (MBD) due to substance use during peri-conception and pregnancy on perinatal outcomes are unclear. The adverse perinatal outcomes of primiparous mothers admitted to hospital with MBD due to substance use before and/or during pregnancy were investigated. Method: This study linked birth and hospital records in NSW, Australia. Subjects included primiparous mothers admitted to hospital for MBD due to use of alcohol, opioids or cannabinoids during peri-conception and pregnancy. Results: There were 304 primiparous mothers admitted to hospital for MBD due to alcohol use (MBDA), 306 for MBD due to opioids use (MBDO) and 497 for MBD due to cannabinoids (MBDC) between the 12 months peri-conception and the end of pregnancy. Primiparous mothers admitted to hospital for MBDA during pregnancy or during both peri-conception and pregnancy were significantly more likely to give birth to a baby of low birthweight (AOR = 4.03, 95%CI: 1.97–8.24 for pregnancy; AOR = 9.21, 95%CI: 3.76–22.57 both periods); preterm birth (AOR = 3.26, 95% CI: 1.52–6.97 for pregnancy; AOR = 4.06, 95%CI: 1.50–11.01 both periods) and admission to SCN or NICU (AOR = 2.42, 95%CI: 1.31–4.49 for pregnancy; AOR = 4.03, 95%CI: 1.72–9.44 both periods). Primiparous mothers admitted to hospital for MBDO, MBDC or a combined diagnosis were almost three times as likely to give birth to preterm babies compared to mothers without hospital admissions for psychiatric or substance use disorders. Babies whose mothers were admitted to hospital with MBDO before and/or during pregnancy were six times more likely to be admitted to SCN or NICU (AOR = 6.29, 95%CI: 4.62–8.57). Conclusion: Consumption of alcohol, opioids or cannabinoids during peri-conception or pregnancy significantly increased the risk of adverse perinatal outcomes.
PMCID: PMC4053897  PMID: 24814946
pregnancy; perinatal outcomes; substance use; alcohol; opioids; cannabinoids
6.  Length of Stay for Mental and Behavioural Disorders Postpartum in Primiparous Mothers: A Cohort Study 
Background: Previous research showed that there was a significant increase in psychiatric hospital admission of postpartum mothers. The aim of the current study is to describe the length of hospital stays and patient days for mental and behavioural disorders (MBD) of new mothers in the first year after birth. Method: This was a cohort study based on linked population data between the New South Wales (NSW) Midwives Data Collection (MDC) and the NSW Admitted Patients Data Collection (APDC). The study population included primiparous mothers aged from 18 to 44 who gave birth between 1 July 2000 and 31 December 2005. The Kaplan–Meier method was used to describe the length of hospital stay for MBD. Results: For principal diagnoses of MBD, the entire length of hospital stay in the first year postpartum was 11.38 days (95% CI: 10.70–12.06) for mean and 6 days (95% CI: 5.87–6.13) for median. The length of hospital stay per admission was 8.47 days (95% CI: 8.03–8.90) for mean and 5 days (95% CI: 4.90–5.10) for median. There were 5,129 patient days of hospital stay per year for principal diagnoses of postpartum MBD in new mothers between 1 July 2000 and 31 December 2005 in NSW, Australia. Conclusions: MBD, especially unipolar depressions, adjustment disorders, acute psychotic episodes, and schizophrenia, or schizophrenia-like disorders during the first year after birth, placed a significant burden on hospital services due to long hospital stays and large number of admissions.
PMCID: PMC4025045  PMID: 24681554
mental health; length of hospital stay; postpartum; data linkage
7.  Silver nanoparticles (AgNPs) cause degeneration of cytoskeleton and disrupt synaptic machinery of cultured cortical neurons 
Molecular Brain  2013;6:29.
Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are being widely used in a broad range of applications. These include, but are not limited to, antibacterial materials, the textile industry, cosmetics, coatings of various household appliances and medical devices. Despite their extensive use, little is known about AgNP safety and toxicity vis-à-vis human and animal health. Recent studies have drawn attention towards potential neurotoxic effects of AgNPs, however, the primary cellular and molecular targets of AgNP action/s remain to be defined.
Here we examine the effects of ultra fine scales (20 nm) of AgNPs at various concentrations (1, 5, 10 and 50 μg/ml) on primary rat cortical cell cultures. We found that AgNPs (at 1-50 μg/ml) not only inhibited neurite outgrowth and reduced cell viability of premature neurons and glial cells, but also induced degeneration of neuronal processes of mature neurons. Our immunocytochemistry and confocal microscopy studies further demonstrated that AgNPs induced the loss of cytoskeleton components such as the β-tubulin and filamentous actin (F-actin). AgNPs also dramatically reduced the number of synaptic clusters of the presynaptic vesicle protein synaptophysin, and the postsynaptic receptor density protein PSD-95. Finally, AgNP exposure also resulted in mitochondria dysfunction in rat cortical cells.
Taken together, our data show that AgNPs induce toxicity in neurons, which involves degradation of cytoskeleton components, perturbations of pre- and postsynaptic proteins, and mitochondrial dysfunction leading to cell death. Our study clearly demonstrates the potential detrimental effects of AgNPs on neuronal development and physiological functions and warns against its prolific usage.
PMCID: PMC3695839  PMID: 23782671
Silver nanoparticles; Rat cortical culture; Toxicity; Cytoskeleton; Synaptic machinery; Mitochondria
8.  Under-reporting of birth registrations in New South Wales, Australia 
To determine the rates of birth registration over a five-year period in New South Wales (NSW) and explore the factors associated with the rate of registration.
This is a cross-sectional study using linked population databases. The study population included all births of NSW residents in NSW between 2001 and 2005.
Birth registration rates in NSW were 82.66% in the year of birth, 93.19% in the first year, 94.02% in the second, 94.56% in the third and 95.08% in the fourth year after birth. The non-registration of births was mainly associated with such factors as neonatal and postneonatal death (adjusted OR = 3.84, 95% CI: 3.23-4.57); being Indigenous (adjusted OR = 3.26, 95% CI: 3.10-3.43); maternal age <25 or >39 years (adjusted OR = 2.81, 95% CI: 2.72-2.90); low birthweight (<2,500 grams) (adjusted OR = 1.79, 95% CI: 1.69-1.90); living in remote areas (adjusted OR = 1.57, 95% CI: 1.52-1.63); being born after the first quarter of year (adjusted OR = 1.08-1.56, 95% CI between 1.03-1.12 and 1.49-1.64); mother having more pregnancies (adjusted OR = 1.85-7.29, 95% CI between1.78-1.93 and 6.87-7.73). Mothers who were born overseas were more likely to register their births than those born in Australia (adjusted OR = 0.72, 95% CI: 0.69-0.75). Multiple births were more likely to be registered than singleton births (adjusted OR = 0.84, 95% CI: 0.76-0.92). About one-third of the non-registrations of births in NSW were explained by the risk factors. The reasons for the remaining non-registrations need to be investigated.
Of birth in NSW, 4.92% were not registered by the fourth year after birth.
PMCID: PMC3562517  PMID: 23234578
Birth; Registration; Factor; Australia
9.  Mercury-induced toxicity of rat cortical neurons is mediated through N-methyl-D-Aspartate receptors 
Molecular Brain  2012;5:30.
Mercury is a well-known neurotoxin implicated in a wide range of neurological or psychiatric disorders including autism spectrum disorders, Alzheimer’s disease, Parkinson’s disease, epilepsy, depression, mood disorders and tremor. Mercury-induced neuronal degeneration is thought to invoke glutamate-mediated excitotoxicity, however, the underlying mechanisms remain poorly understood. Here, we examine the effects of various mercury concentrations (including pathological levels present in human plasma or cerebrospinal fluid) on cultured, rat cortical neurons.
We found that inorganic mercuric chloride (HgCl2 –at 0.025 to 25 μM) not only caused neuronal degeneration but also perturbed neuronal excitability. Whole-cell patch-clamp recordings of pyramidal neurons revealed that HgCl2 not only enhanced the amplitude and frequency of synaptic, inward currents, but also increased spontaneous synaptic potentials followed by sustained membrane depolarization. HgCl2 also triggered sustained, 2–5 fold rises in intracellular calcium concentration ([Ca2+]i). The observed increases in neuronal activity and [Ca2+]i were substantially reduced by the application of MK 801, a non-competitive antagonist of N-Methyl-D-Aspartate (NMDA) receptors. Importantly, our study further shows that a pre incubation or co-application of MK 801 prevents HgCl2-induced reduction of cell viability and a disruption of β-tubulin.
Collectively, our data show that HgCl2-induced toxic effects on central neurons are triggered by an over-activation of NMDA receptors, leading to cytoskeleton instability.
PMCID: PMC3462706  PMID: 22980357
Mercury Chloride; Rat cortical neurons; Toxicity; MK 801; NMDA receptor; Excitotoxicity; Cytoskeleton
10.  Data preparation techniques for a perinatal psychiatric study based on linked data 
In recent years there has been an increase in the use of population-based linked data. However, there is little literature that describes the method of linked data preparation. This paper describes the method for merging data, calculating the statistical variable (SV), recoding psychiatric diagnoses and summarizing hospital admissions for a perinatal psychiatric study.
The data preparation techniques described in this paper are based on linked birth data from the New South Wales (NSW) Midwives Data Collection (MDC), the Register of Congenital Conditions (RCC), the Admitted Patient Data Collection (APDC) and the Pharmaceutical Drugs of Addiction System (PHDAS).
The master dataset is the meaningfully linked data which include all or major study data collections. The master dataset can be used to improve the data quality, calculate the SV and can be tailored for different analyses. To identify hospital admissions in the periods before pregnancy, during pregnancy and after birth, a statistical variable of time interval (SVTI) needs to be calculated. The methods and SPSS syntax for building a master dataset, calculating the SVTI, recoding the principal diagnoses of mental illness and summarizing hospital admissions are described.
Linked data preparation, including building the master dataset and calculating the SV, can improve data quality and enhance data function.
PMCID: PMC3445825  PMID: 22682616
Data preparation; Method; Psychiatric study; Australia
11.  Improvement of maternal Aboriginality in NSW birth data 
The Indigenous population of Australia was estimated as 2.5% and under-reported. The aim of this study is to improve statistical ascertainment of Aboriginal women giving birth in New South Wales.
This study was based on linked birth data from the Midwives Data Collection (MDC) and the Registry of Births Deaths and Marriages (RBDM) of New South Wales (NSW). Data linkage was performed by the Centre for Health Record Linkage (CHeReL) for births in NSW for the period January 2001 to December 2005. The accuracy of maternal Aboriginal status in the MDC and RBDM was assessed by consistency, sensitivity and specificity. A new statistical variable, ASV, or Aboriginal Statistical Variable, was constructed based on Indigenous identification in both datasets. The ASV was assessed by comparing numbers and percentages of births to Aboriginal mothers with the estimates by capture-recapture analysis.
Maternal Aboriginal status was under-ascertained in both the MDC and RBDM. The ASV significantly increased ascertainment of Aboriginal women giving birth and decreased the number of missing cases. The proportion of births to Aboriginal mothers in the non-registered birth group was significantly higher than in the registered group.
Linking birth data collections is a feasible method to improve the statistical ascertainment of Aboriginal women giving birth in NSW. This has ramifications for the ascertainment of babies of Aboriginal mothers and the targeting of appropriate services in pregnancy and early childhood.
PMCID: PMC3314542  PMID: 22289717
Birth; Aboriginality; data; Australia
12.  Quercetin Targets Cysteine String Protein (CSPα) and Impairs Synaptic Transmission 
PLoS ONE  2010;5(6):e11045.
Cysteine string protein (CSPα) is a synaptic vesicle protein that displays unique anti-neurodegenerative properties. CSPα is a member of the conserved J protein family, also called the Hsp40 (heat shock protein of 40 kDa) protein family, whose importance in protein folding has been recognized for many years. Deletion of the CSPα in mice results in knockout mice that are normal for the first 2–3 weeks of life followed by an unexplained presynaptic neurodegeneration and premature death. How CSPα prevents neurodegeneration is currently not known. As a neuroprotective synaptic vesicle protein, CSPα represents a promising therapeutic target for the prevention of neurodegenerative disorders.
Methodology/Principal Findings
Here, we demonstrate that the flavonoid quercetin promotes formation of stable CSPα-CSPα dimers and that quercetin-induced dimerization is dependent on the unique cysteine string region. Furthermore, in primary cultures of Lymnaea neurons, quercetin induction of CSPα dimers correlates with an inhibition of synapse formation and synaptic transmission suggesting that quercetin interfers with CSPα function. Quercetin's action on CSPα is concentration dependent and does not promote dimerization of other synaptic proteins or other J protein family members and reduces the assembly of CSPα:Hsc70 units (70kDa heat shock cognate protein).
Quercetin is a plant derived flavonoid and popular nutritional supplement proposed to prevent memory loss and altitude sickness among other ailments, although its precise mechanism(s) of action has been unclear. In view of the therapeutic promise of upregulation of CSPα and the undesired consequences of CSPα dysfunction, our data establish an essential proof of principle that pharmaceutical agents can selectively target the neuroprotective J protein CSPα.
PMCID: PMC2883571  PMID: 20548785
13.  Breastfeeding in China: a review 
This review aims to describe changes in breastfeeding and summarise the breastfeeding rates, duration and reasons of discontinuing 'any breastfeeding' or 'exclusive breastfeeding' in P.R. China. Breastfeeding rates in China fell during the 1970s when the use of breast milk substitutes became widespread, and reached the lowest point in the 1980s. As a result many efforts were introduced to promote breastfeeding. The breastfeeding rate in China started to increase in the 1990s, and since the mid-1990s 'any breastfeeding' rates in the majority of cities and provinces, including minority areas, have been above 80% at four months. But most cities and provinces did not reach the national target of 'exclusive breastfeeding' of 80%. The 'exclusive breastfeeding' rates in minority areas were relatively lower than comparable inland provinces. The mean duration of 'any breastfeeding' in the majority of cities or provinces was between seven and nine months. The common reasons for ceasing breastfeeding, or introducing water or other infant food before four months, were perceived breast milk insufficiency, mother going to work, maternal and child illness and breast problems. Incorrect traditional perceptions have a strong adverse influence on 'exclusive breastfeeding' in less developed areas or rural areas. China is a huge country, geographically and in population size, and there is considerable ethnic diversity. Therefore breastfeeding rates in different parts of China can vary considerably.
PMCID: PMC2706212  PMID: 19531253
14.  A decade of change in breastfeeding in China's far north-west 
There have been considerable changes in breastfeeding practices in China over the past forty years. However China is a very large country, and breastfeeding rates in different parts of China vary considerably. The objective of this paper is to identify and compare breastfeeding types and rates between 1994–1996 and 2003–2004 in Shihezi, Xinjiang Uygur Autonomous Region, PR China.
In 1994–1996, a study of breastfeeding (n = 2197) was undertaken in Shihezi, Xinjiang, PR China. A decade later in 2003–2004, a longitudinal study (n = 545) of infant feeding practices was undertaken in the same area.
The 'any breastfeeding' rates at 1, 4 and 6 months were 94%, 82% and 78% respectively in the early 1990s. A decade later, breastfeeding at 1 month was lower, but rates at 4 and 6 months remained the same. In 2004 the 'full breastfeeding' rate at one month was significantly higher (57%) than a decade earlier (38%), but after 3 months there was a rapid decline. This reflected a shift in the way complementary foods are introduced: the initial introduction was later, but by a higher proportion of mothers.
The rate of breastfeeding at one month is significantly lower in 2003–2004 when compared to 1994–1996. The 'full breastfeeding' rates were initially higher, but after 3 months were then lower. The Chinese national breastfeeding targets were not reached in either period of the study. These studies show the need to further promote full or exclusive breastfeeding and further longitudinal studies are necessary to provide the detailed knowledge about risk factors required for health promotion programs.
PMCID: PMC1702342  PMID: 17123450
15.  A comparison of breastfeeding among Han, Uygur and other ethnic groups in Xinjiang, PR China 
BMC Public Health  2006;6:196.
Breastfeeding is an important factor in infant health and there have been no previous studies of breastfeeding practices in the different ethnic groups of this region of China. We aimed to compare breastfeeding rates and duration between Han, Uygur and other ethnic groups living in Xinjiang, PR China.
A longitudinal study of infant feeding practices was undertaken using a sample that included different ethnic groups. Mothers were randomly recruited and interviewed in hospitals and after discharge were contacted in person or by telephone at approximately monthly intervals to obtain details of infant feeding practices. Setting: Xinjiang Uygur Autonomous Region, PR China. Subjects: A total of1219 mothers (578 Han, 360 Uygur and 281 'other minority' mothers) who delivered babies during 2003 and 2004 were interviewed in five hospitals or institutes located in both urban and rural areas.
'Any breastfeeding' rates in Han, Uygur and 'other minority' groups at discharge were 88.5 %, 94.3 % and 97.1 % respectively, and at six months 76.7 %, 54.7 % and 87.6 % respectively. While 'exclusive breastfeeding' rates in the Han, Uygur and 'other minority' groups at discharge were 78.0 %, 34.5 % and 83.1 % respectively, at six months they had fallen to 4.8 %, 0.4 % and 16.8 % respectively. The median duration of 'Exclusive breastfeeding' of Han, Uygur and 'other minority' babies were 1.5, 0.1 and 2.5 months respectively. The Uygur babies were least likely to be 'exclusive breastfed'.
Uygur babies were least likely to be 'exclusive breastfed' and continued to 'any breastfeed' at six month. The 'any breastfeeding' rates in the Han group were lower in the first four months. An education program focused on breastfeeding continuation and exclusive breastfeeding is necessary in Xinjiang, especially for Uygur and Han ethnic groups.
PMCID: PMC1555591  PMID: 16872508

Results 1-15 (15)