Staying close to home? Genetic differentiation of rough-toothed dolphins near oceanic islands in the central Pacific Ocean

Rough-toothed dolphins have a worldwide tropical and subtropical distribution, yet little is known about the population structure and social organization of this typically open-ocean species. Although it has been assumed that pelagic dolphins range widely due to the lack of apparent barriers and unpredictable prey distribution, recent evidence suggests rough-toothed dolphins exhibit fidelity to some oceanic islands. Using the most comprehensively extensive dataset for this species to date, we assess the isolation and interchange of rough-toothed dolphins at the regional and oceanic scale within the central Pacific Ocean. Using mtDNA and microsatellite genotyping (nDNA), we analyzed samples of insular communities from the main Hawaiian (Kaua‘i n = 93, O‘ahu n = 9, Hawai‘i n = 57), French Polynesian (n = 70) and Samoan (n = 16) archipelagos, and pelagic samples off the Northwestern Hawaiian Islands (n = 18). An overall AMOVA indicated strong genetic differentiation among islands (mtDNA F_ST = 0.265; p < 0.001; nDNA F_ST = 0.038; p < 0.001), as well as among archipelagos (mtDNA F_ST = 0.299; p < 0.001; nDNA F_ST = 0.055; p < 0.001). Shared haplotypes (n = 4) between the archipelagos may be a product of a relatively recent divergence and/or periodic exchange from poorly understood pelagic populations. Analyses using STRUCTURE and GENELAND identified four separate management units among archipelagos and within the Hawaiian Islands. These results confirm the presence of multiple insular populations within the Pacific and island-specific genetic isolation among populations attached to islands in each archipelago. Insular populations seem most prevalent where oceanographic conditions indicate high local productivity or a discontinuity with surrounding oligotrophic areas. Our findings have important implications for a little studied species that faces increasing anthropogenic threats around oceanic islands.     

Validation of Orthopedic Postoperative Pain Assessment Methods for Dogs: A Prospective,Blinded, Randomized,Placebo-Controlled Study

In the context of translational research, there is growing interest in studying surgical orthopedic pain management approaches that are common to humans and dogs. The validity of postoperative pain assessment methods is uncertain with regards to responsiveness and the potential interference of analgesia. The hypothesis was that video analysis (as a reference), electrodermal activity, and two subjective pain scales (VAS and 4A-VET) would detect different levels of pain intensity in dogs after a standardized trochleoplasty procedure. In this prospective, blinded, randomized study, postoperative pain was assessed in 25 healthy dogs during a 48-hour time frame (T). Pain was managed with placebo (Group 1, n = 10), preemptive and multimodal analgesia (Group 2, n = 5), or preemptive analgesia consisting in oral tramadol (Group 3, n = 10). Changes over time among groups were analyzed using generalized estimating equations. Multivariate regression tested the significance of relationships between pain scales and video analysis. Video analysis identified that one orthopedic behavior, namely ‘Walking with full weight bearing’ of the operated leg, decreased more in Group 1 at T24 (indicative of pain), whereas three behaviors indicative of sedation decreased in Group 2 at T24 (all p<0.004). Electrodermal activity was higher in Group 1 than in Groups 2 and 3 until T1 (p<0.0003). The VAS was not responsive. 4A-VET showed divergent results as its orthopedic component (4A-VETleg) detected lower pain in Group 2 until T12 (p<0.0009), but its interactive component (4A-VETbeh) was increased in Group 2 from T12 to T48 (p<0.001). Concurrent validity established that 4A-VETleg scores the painful orthopedic condition accurately and that pain assessment through 4A-VETbeh and VAS was severely biased by the sedative side-effect of the analgesics. Finally, the video analysis offered a concise template for assessment in dogs with acute orthopedic pain. However, subjective pain quantification methods and electrodermal activity need further investigation.     

Acupuncture: it take the pain away?

Acupuncture is growing in popularity in most Western countries and continues to be a major form of medicine in China and Japan. In the USA, an estimated ten million consultations for acupuncture take place each year. Many scientists regard acupuncture, like many other ‘alternative’ therapies, as an over-dressed placebo that fulfills a need for mysticism and ancient ritual. But if we dismiss acupuncture in this way, are we rejecting an opportunity to learn more about the body's response to pain?     

Combined Low-Intensity Exercise and Ascorbic Acid Attenuates Kainic Acid-Induced Seizure and Oxidative Stress in Mice

Physical exercise and vitamins such as ascorbic acid (ASC) have been recognized as an effective strategy in neuroprotection and neurorehabilitatioin. However, there is a need to find an efficient treatment regimen that includes ASC and low-intensity exercise to diminish the risk of overtraining and nutritional treatment by attenuating oxidative stress. In the present study, we investigated the combined effect of low-intensity physical exercise (EX) and ASC on kainic acid (KA)-induced seizure activity and oxidative stress in mice. The mice were randomly assigned into groups as follows: “KA only” (n = 11), “ASC + KA” (n = 11), “Ex + KA” (n = 11), “ASC + Ex + KA” (n = 11). In the present study, low intensity of swimming training period lasted 8 weeks and consisted of 30-min sessions daily (three times per week) without tail weighting. Although no preventive effect of low-intensity exercise or ASC on KA seizure occurrence was evident, there was a decrease of seizure activity, seizure development (latency to first seizures), and mortality in “ASC + Ex + KA” compared to “ASC + KA”, “Ex + KA”, and “KA only” group. In addition, a preventive synergistic coordination of low-intensity exercise and ASC was evident in glutathione peroxidase and superoxide dismutase activity compared to separate treatment. These results suggest that low-intensity exercise and ASC treatment have preventive effects on seizure activity and development with alternation of oxidative status.     

Evaluation of the efficacy of a novel electronic pain assessment device, the Pain Gauge, for measuring postoperative pain in rats

One of the major challenges for individuals working with laboratory animals is the recognition and alleviation of pain. The Pain Gauge is marketed as a pain assessment device that measures electrodermal activity. To establish whether the Pain Gauge is effective in assessing postoperative pain in laboratory rats, preoperative and postoperative pain gauge scores ('pain scores') were obtained from 67 rats. Rats were randomly assigned to one of three experimental groups (laparotomy, craniotomy or control) and to one of four analgesic groups (meloxicam [2 mg/kg s.c.] or parecoxib [1, 5 or 20 mg/kg i.v.]). Five consecutive 'pain scores' were obtained from each animal at each of five time points (preprocedure, and at 1, 2, 3 and 4 h postoperatively). Overall there was a significant difference between 'pain scores' at different time points; mainly a decrease at 1 h postoperatively compared with the preoperative scores. There was no overall increase in postoperative 'pain scores' in the rats that were most likely to suffer from postoperative pain (rats given a lower dose of analgesic that underwent a surgical procedure) compared with rats that did not undergo a potentially painful procedure (rats in anaesthesia-only/control group). Therefore it was concluded that the Pain Gauge is ineffective in assessing postoperative pain in rats in this study.     

Characterization of methicillin-resistant coagulase-negative staphylococci in milk from cows with mastitis in Brazil

Staphylococci are one of the most prevalent microorganisms in bovine mastitis. Staphylococcus spp. are widespread in the environment, and can infect animals and humans as opportunistic pathogens. The objective of this study was to determine the frequency of methicillin-resistance (MR) among coagulase-negative staphylococci (CoNS) previously obtained from milk of mastitic cows in Brazil and to characterize the antimicrobial resistance phenotype/genotype and the SCCmec type of MRCoNS isolates. Identification of MRCoNS was based on both biochemical and molecular methods. Susceptibility testing for eleven antimicrobials was performed by disk-diffusion agar. Antimicrobial resistance genes and SCCmec were investigated by specific PCRs. Twenty-six MRCoNS were detected (20 % of total CoNS), obtained from 24 animals, and were identified as follows: S. epidermidis (7 isolates), S. chromogenes (7), S. warneri (6), S. hyicus (5) and S. simulans (1). All MRCoNS isolates carried mecA while the mecC gene was not detected in any CoNS. The SCCmec IVa was demonstrated in nine MRCoNS, while the remaining 17 isolates harbored non-typeable SCCmec cassettes. In addition to oxacillin and cefoxitin resistance, MRCoNS showed resistance to tetracycline (n = 7), streptomycin (n = 6), tobramycin (n = 6), and gentamicin (n = 4), and harbored the genes tet(K) (n = 7), str (n = 3), ant(4′) (n = 6) and aac(6′)-aph(2″) (n = 4), respectively. In addition, seven strains showed intermediate resistance to clindamycin and two to streptomycin, of which two harboured the lnu(B) and lsa(E) genes and two the aad(E) gene, respectively. One isolate presented intermediate erythromycin and clindamycin resistance and harbored an erm(C) gene with an uncommon 89-bp deletion rendering a premature stop codon. MRCoNS can be implicated in mastitis of cows and they constitute a reservoir of resistance genes that can be transferred to other pathogenic bacteria.     

The optimized acupuncture treatment for neck pain caused by cervical spondylosis: a study protocol of a multicentre randomized controlled trial

ABSTRACT: BACKGROUND: Neck pain is one of the chief complains of patients with cervical spondylosis (CS). Both in China and worldwide, acupuncture is a well-accepted and widely used complementary therapy for the management of neck pain caused by CS. In this paper, we present a protocol designed for a multi-centre, randomised, controlled trial to evaluate the effects of optimised acupuncture treatment for CS neck pain. The study aims to evaluate the effects of the optimised acupuncture treatment in real practice compared with sham and shallow acupuncture therapy. Methods/design This trial uses a multicentre, three-group, randomised, sham acupuncture and shallow acupuncture, controlled single-blind design. Nine hospitals are involved as trial centres. The sample size is calculated based on the formula for a three-group parallel design with a 0.05 significance level and a power of 0.9. A total of 105 cases in a single centre, and a total of 315 cases per each arm are required across all 9 centres. Patients who meet inclusion criteria are randomly assigned to receive optimised acupuncture treatment, sham acupuncture or shallow acupuncture by a computerised central randomisation system. The interventions last for 4 weeks with 8 to 10 treatments. The group allocations and interventions are concealed to patients and statisticians. The Northwick Park Neck Pain Questionnaire (NPQ) is used as the primary outcome measure, and the McGill Pain Questionnaire (MPQ) and The Short Form (36) Health Survey (SF-36) are applied as secondary outcome measures. The evaluation is performed at baseline, at the end of the intervention, and at the end of the first month and the third month during follow-up. The statistical analyses will include baseline data comparison and repeated measures of analysis of variance (ANOVA) for primary and secondary outcomes of group and time differences. Adverse events (AEs) will be reported if they occur. DISCUSSION: This trial is a multicentre randomised control trial (RCT) on the efficacy of acupuncture for CS neck pain and has a large sample size and central randomisation in China. It will strictly follow the CONSORT statement and STRICTA extension guideline to report high-quality study results. By setting the control groups as sham and shallow acupuncture, this study attempts to reveal the effects of real acupuncture versus placebo or non-classic acupuncture therapy and evaluate whether classic Chinese medical acupuncture is effective on CS neck pain. This study will provide evidence for the effects of acupuncture on CS neck pain. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-TRC-00000184.     

The association between sleep chronotype and obesity among black and white participants of the Bogalusa Heart Study

ABSTRACT

Research indicates that sleep duration and quality are inter-related factors that contribute to obesity, but few studies have focused on sleep chronotype, representing an individual’s circadian proclivity, nor assessed these factors in racially diverse middle-aged samples. We examined the associations between chronotype and obesity among black and white men and women participating in the Bogalusa Heart Study (BHS).

Body mass index (BMI) and sleep data were available for 1,197 middle-aged men and women (mean age 48.2 ± 5.3 years) who participated in the BHS 2013–2016. Based on the reduced Morningness-Eveningness Questionnaire’s cutoff values for chronotypes, we combined ‘definitely morning’ and ‘moderately morning’ types into ‘morning’ type, ‘definitely evening’ and ‘moderately evening’ types into ‘evening’ type and kept those who were “neither” type in a separate group. We used ‘morning’ type as the referent group. Obesity was defined as a BMI ≥ 30. Multivariable logistic regression models were used to examine associations adjusting for sex, age, education, smoking, alcohol use and drug use, depression, shift work, physical activity and sleep duration.

Evening chronotype, reported by 11.1% of participants, was associated with obesity after multi-variable adjustment, including shift work, physical activity and sleep duration (OR 1.67, 95% CI: 1.08–2.56). However, once stratified by race (black/white), this association was found only among white participants (OR = 1.91, 95% CI = 1.12–3.25) after full adjustment.

In our biracial, community-based population, evening chronotype was independently associated with obesity, specifically among white participants. Further research is needed to identify behavioral, endocrine, nutritional and genetic pathways which underlie these associations.     

Point of Care Tuberculosis Sero-Diagnosis Kit for Wild Animals: Combination of Proteins for Improving the Diagnostic Sensitivity and Specificity

Tuberculosis is a significant problem globally for domestic animals as well as captive and free ranging wild life. Rapid point of care (POC) serology kits are well suited for the diagnosis of TB in wild animals. However, wild animals are invariably exposed to environmental non-pathogenic mycobacterium species with the development of cross reacting antibodies. In the present study, POC TB diagnosis kit was developed using a combination of pathogenic Mycobacteria specific recombinant antigens and purified protein derivatives of pathogenic and non-pathogenic Mycobacteria. To benchmark the TB antibody detection kit, particularly in respect to specificity which could not be determined in wildlife due to the lack of samples from confirmed uninfected animals, we first tested well-characterized sera from 100 M. bovis infected and 100 uninfected cattle. Then we investigated the kit’s performance using sera samples from wildlife, namely Sloth Bears (n = 74), Elephants (n = 9), Cervidae (n = 14), Felidae (n = 21), Cape buffalo (n = 2), Wild bear (n = 1) and Wild dog (n = 1).In cattle, a sensitivity of 81% and a specificity of 90% were obtained. The diagnostic sensitivity of the kit was 94% when the kit was tested using known TB positive sloth bear sera samples. 47.4% of the in-contact sloth bears turned seropositive using the rapid POC TB diagnostic kit. Seropositivity in other wild animals was 25% when the sera samples were tested using the kit. A point of care TB sero-diagnostic kit with the combination of proteins was developed and the kit was validated using the sera samples of wild animals.     

Construction of a high-density genetic map of <Emphasis Type="Italic">Ziziphus jujuba</Emphasis> Mill. using genotyping by sequencing technology

The Chinese jujube (Ziziphus jujuba Mill., 2n = 2 × = 24), one of the most popular fruit trees in China, is widely cultivated and utilized in Asia. High-density genetic linkage maps are valuable resources for molecular breeding and functional genomics; however, they are still under-developed for the jujube. The genotyping by sequencing (GBS) strategy could be an efficient and cost-effective tool for single nucleotide polymorphism (SNP) discovery based on the sequenced jujube genome. Here, we report a new high-density genetic map constructed using GBS technology. An F1 population with 145 progenies and their parents (‘Dongzao’ × ‘Zhongningyuanzao’) were sequenced on the Illumina HiSeq 4000 platform. In total, 79.8 Gb of raw data containing 256,708,177 paired-end reads were generated. After data filtering and SNP genotyping, 40,372 polymorphic SNP markers were developed between the parents and 2540 (1756 non-redundant) markers were mapped onto the integrated genetic linkage map. The map spanned 1456.53 cM and was distributed among 12 linkage groups, which is consistent with the haploid chromosome number of the jujube. The average marker interval was 0.88 cM. The genetic map allowed us to anchor 224 Mb (63.7 %) of scaffolds from the sequenced ‘Junzao’ genome, containing 52 newly anchored scaffolds, which extended the genome assembly by 7 Mb. In conclusion, GBS technology was applied efficiently for SNP discovery in this study. The high-density genetic map will serve as a unique tool for molecular-assisted breeding and genomic studies, which will contribute to further research and improvement of the jujube in the near future.     

A pluralist challenge to “integrative medicine”: Feyerabend and Popper on the cognitive value of alternative medicine

This paper is a critique of ‘integrative medicine’ as an ideal of medical progress on the grounds that it fails to realise the cognitive value of alternative medicine. After a brief account of the cognitive value of alternative medicine, I outline the form of ‘integrative medicine’ defended by the late Stephen Straus, former director of the US National Centre for Complementary and Alternative Medicine. Straus’ account is then considered in the light of Zuzana Parusnikova’s recent criticism of ‘integrative medicine’ and her distinction between ‘cognitive’ and ‘opportunistic’ engagement with alternative medicine. Parusnikova warns that the medical establishment is guilty of ‘dogmatism’ and proposes that one can usefully invoke Karl Popper’s ‘critical rationalism’ as an antidote. Using the example of Straus, I argue that an appeal to Popper is insufficient, on the grounds that ‘integrative medicine’ can class as a form of cognitively-productive, critical engagement. I suggest that Parusnikova’s appeal to Popper should be augmented with Paul Feyerabend’s emphasis upon the role of ‘radical alternatives’ in maximising criticism. ‘Integrative medicine’ fails to maximise criticism because it ‘translates’ alternative medicine into the theories and terminology of allopathic medicine and so erodes its capacity to provide cognitively-valuable ‘radical alternatives’. These claims are then illustrated with a discussion of ‘traditional’ and ‘medical’ acupuncture. I conclude that ‘integrative medicine’ fails to exploit the cognitive value of alternative medicine and so should be rejected as an ideal of medical progress.     

Estuarine fish behavior around slotted water control structures in a managed salt marsh

Estuaries are composed of multiple interconnected habitat types used by transient fish species during their period of estuarine residency. Structural marsh management restricts habitat connectivity and impedes the movement of fishes among these habitat types by limiting access via water control structures (WCSs) between the managed area and the rest of the estuary. While some general information on fish passage rates is available, species-specific information on passage through WCSs is lacking for salt marsh fishes. We monitored tagged fishes from March 2012 through November 2013 using passive integrated transponder antenna arrays at two identical WCSs in the Calcasieu Lake estuary, Louisiana, USA, to assess the effect of slotted WCSs on fish behavior. A total of 420 individuals of 15 species was tagged and released at the WCSs; of these, 145 individuals representing 11 species were later detected at the WCSs. Five species comprised most (93%) of the detected individuals: Elops saurus (n = 60), Mugil cephalus (n = 43), Sciaenops ocellatus (n = 20), Pogonias cromis (n = 7), and Ariopsis felis (n = 5). Passage rates were low, with most of the observed fishes (n = 80) passing only once through the structures. Other than E. saurus, which was only observed migrating out of the managed marsh, no clear pattern in swimming direction was observed for the other species. Detected species were all present primarily during the summer and fall, however, diel activity at the structures varied by species. The WCSs in our study area appeared to attract and congregate fishes, functioning more like ecological hotspots, rather than simply facilitating fish passage.     

Tetraploid induction of Mitracarpus hirtus L. by colchicine and its characterization including antibacterial activity

Tetraploid plants were successfully induced for the first time in Mitracarpus hirtus L., by overnight immersion of shoot meristems in 0.1 % colchicine solution, followed by in vitro culture leading to plant regeneration. Examination of ploidy level by flow cytometric analysis and counting chromosome number at metaphase confirmed that original diploid plant (WT1) contained chromosome number as 2n = 2x = 28, whereas 2n = 4x = 56 was observed in the tetraploids induced with colchicine treatment (CC102 and CC110). Thicker root formation, larger stomata (1.3–2 times), and lower density of stomata (1.7–4 times) were observed in these tetraploid plants. After transplantation to the pot, tetraploid plant (CC110) showed higher fresh weights of aerial part and leaves (1.5 and 1.4 times respectively) than diploid. However, the methanolic extracts from leaves of tetraploid line CC102 showed inhibition against human pathogenic bacterium, S. aureus while WT1 and CC110 showed no activity. GC–MS revealed 40 unique compounds present in CC102, but absent in WT1 and CC110. Through hierarchical clustering analysis the 40 unique compounds in CC102 formed a cluster group found to correlate with anti-S. aurens activity. These results suggested that tetraploid M. hirtus CC102 created in this study provides a novel source of compounds useful in fighting infectious disease.     

An indigenous community-based monitoring system for assessing forest health in New Zealand

The underlying ethos of ‘nature’s benefits’ contributing to human wellbeing provides a common platform for understanding the function and value of biodiversity for stakeholders. Diverse societal worldviews however create differences in the way cultures relate to and understand the environment. The objective of this study was to identify community-based indicators and metrics used by Māori in New Zealand to monitor forest health and community wellbeing. Eighty semi-directed interviews were conducted with 55 forest users within the Tuawhenua tribal group to identify forest health indicators and associated gradient of metrics to assess each indicator. Indicators were grouped within nine culturally-relevant themes: (1) food procurement (mahinga kai), (2) natural productivity (hua o te whenua), (3) nature of water (āhua o te wai), (4) nature of the land (āhua o te whenua), (5) nature of the forest (āhua o te ngahere), (6) perpetual occupation of land and place (ahikaaroa), (7) spiritual dimension (taha wairua), (8) physical health (taha kikokiko), and (9) mental health (taha hinengaro). Within these themes, indicators and associated metrics were aligned within two monitoring approaches: field survey and interview-based. Community members (n = 35 individuals) were asked to prioritise field survey indicators using a seven point Likert Scale of importance. A second survey was also conducted with Tuawhenua elders (n = 43 individuals) to determine changes in the frequency of forest use by the community. A decline in the proportion of the community venturing into the forest over the last 60 years for activities such as hunting, fishing, camping, and collecting plant resources was reported. This decline in regular forest use suggests a field survey approach would be an effective method for applying community-based indicators and to gain an understanding of forest health. Forest indicators that are evaluated over a longer timeframe (months, seasons or even years), or those indicators aligned with community wellbeing, would be better evaluated using an interview-based approach. The alignment of some community-based indicators with scientific-based measures would enrich and deepen knowledge about the state of biodiversity, broaden the relevance of monitoring and reporting within indigenous communities, and help to mitigate issues of ‘shifting baselines’.     

Trends in paediatric and adult bloodstream infections at a Ghanaian referral hospital: a retrospective study

Background

Bloodstream infections (BSI) are life-threatening emergencies. Identification of the common pathogens and their susceptibility patterns is necessary for timely empirical intervention.

Methods

We conducted a 4-year retrospective analysis of blood cultures from all patients excluding neonates at the Korle-Bu Teaching hospital, Ghana, from January 2010 through December 2013. Laboratory report data were used to determine BSI, blood culture contamination, pathogen profile, and antimicrobial resistance patterns.

Results

Overall, 3633 (23.16 %) out of 15,683 blood cultures were positive for various organisms. Pathogen-positive cultures accounted for 1451 (9.3 %, 95 % CI 8.5–9.8 %). Infants recorded the highest true blood culture positivity (20.9 %, n = 226/1083), followed by the elderly (13.3 %, n = 80/601), children (8.9 %, n = 708/8000) and adults (7.2 %, n = 437/6000) (p = 0.001 for Marascuilo’s post hoc). Overall occurrence of BSI declined with increasing age-group (p = 0.001) but the type of isolates did not vary with age except for Citrobacter, Escherichia coli, Klebsiella, Salmonella, and Enterococcus species. Gram negative bacteria predominated in our study (59.8 %, n = 867/1451), but the commonest bacterial isolate was Staphylococcus aureus (21.9 %, n = 318/1451)—and this trend run through the various age-groups. From 2010 to 2013, we observed a significant trend of yearly increase in the frequency of BSI caused by cephalosporin-resistant enterobacteria (Chi square for trend, p = 0.001). Meropenem maintained high susceptibility among all Gram-negative organisms ranging from 96 to 100 %. Among Staphylococcus aureus, susceptibility to cloxacillin was 76.6 %.

Conclusion

Our study shows a significantly high blood culture positivity in infants as compared to children, adults and the elderly. There was a preponderance of S. aureus and Gram-negative bacteria across all age-groups. Meropenem was the most active antibiotic for Gram-negative bacteria. Cloxacillin remains a very useful anti-staphylococcal agent.

     

Genetic association study of adaptor protein complex 4 with cerebral palsy in a Han Chinese population

Adaptor protein complex 4 (AP-4) plays a key role in vesicle formation, trafficking, and sorting processes that are critical for brain development and function. AP-4 consists of four subunits encoded by the AP4E1, AP4B1, AP4M1, and AP4S1 genes. A number of studies have pointed to the involvement of AP-4–mediated vesicular trafficking pathways in the etiology of cerebral palsy (CP), the most notable of which are the causative mutations that have recently been identified in each of the AP-4 genes in different CP families. We postulated, therefore, that variations in AP-4 genes might influence an indivual’s susceptibility to CP. In the present study, 16 SNPs were genotyped among 517 CP patients and 502 healthy controls from the Han Chinese population. We systematically analyzed the association of the AP4E1, AP4B1, AP4M1, and AP4S1 genes with CP on the basis of clinical characteristics. No significant associations were found between these variants and the overall risk of CP. Subgroup analysis showed that rs1217401 of AP4B1 was significantly associated with CP as a sequela of hypoxic-ischemic encephalopathy (HIE) (CP + HIE) (allele: p = 0.042151; genotype: p = 4.46 × 10^?6). Our results indicate that the 16 variants studied in the genes of the four subunits of AP-4 have no detectable effects on the overall susceptibility to CP, but AP4B1 appears to be a susceptibility gene for CP + HIE in the Han Chinese population.     

The Effects of Heart Rate Variability Biofeedback in Patients with Preterm Labour

Preterm birth is a highly prevalent phenomenon that was shown to be associated with mental stress during pregnancy (Rich-Edwards and Grizzard in Am J Obstet Gynecol 192(5 Suppl):S30–S35, 2005). We aimed to assess the effects of heart rate variability (HRV)-biofeedback in patients with preterm labour. Therefore, we conducted a controlled randomized parallel group study in 48 female patients aged 19–38 years (median = 29) with preterm labour at gestational week 24th–32nd (median = 29th). In this study, one group (n = 24) attended six sessions of HRV-biofeedback over 2 weeks whereas patients of the other group (n = 24) were assigned to control sessions. In the HRV-biofeedback treated group, perception of chronic stress was decreased 4 weeks after completion of training compared to baseline (p < 0.05) but there was no change in the control group. In the HRV-biofeedback group, preterm birth was seen in 3 patients (13 %) whereas in the control group, preterm delivery occurred in 8 patients (33 %, p = n.s.). There was no difference in birth weight between groups and HRV remained unchanged. In conclusion, our study demonstrates that HRV-biofeedback can reduce chronic stress in patients with preterm labour when administered as an adjunct to routine care. However, it remains unclear whether stress reduction through HRV-biofeedback has a beneficial effect on preterm birth.     

Hippocampal Glutamate Level and Glutamate Aspartate Transporter (GLAST) are Up-Regulated in Senior Rat Associated with Isoflurane-Induced Spatial Learning/Memory Impairment

Postoperative cognitive decline is a clinical concern especially for senior patients. It is generally recognized that glutamatergic system plays a crucial role in the physiopathologic process of neurocognitive deterioration. However, alterations of glutamatergic system in prolonged isoflurane-induced learning/memory decline are still unclear. This study investigates the question whether glutamate concentration and corresponding transporters or receptors display any alternations in aged rat suffering from isoflurane-induced learning/memory impairment. 111 male Sprague–Dawley rats (>18 months) were randomly divided into two main groups: hippocampal microdialysis group (n = 38) and western blotting group (n = 73). Each group was subdivided into three subgroups including (1) control subgroup (n = 6 and 10, receiving no behavioral trial, anesthesia or air exposure); (2) air-exposed subgroup (n = 7 and 15, receiving behavioral trial and air exposure but not anesthesia); (3) isoflurane anesthesia subgroup (n = 25 and 48, receiving both behavioral trial and anesthesia). The isoflurane-exposed rats were further divided into a learning/memory-impaired subgroup and a non-learning/memory-impaired subgroup according to their behavioral performance, which was measured using Morris water maze. Hippocampal glutamate concentrations in microdialysates were determined by high-performance liquid chromatography. Expression levels of GLAST, GLT-1, NMDAR1, NMDAR2A/B, AMPAR and tau in hippocampus were assessed via quantitative Western blotting. The incidences of learning/memory impairment of isoflurane-exposed rats in hippocampal microdialysis group and western blotting group were 12.0 (3/25) and 10.4 % (5/48) respectively. The intra-anesthesia hippocampal glutamate levels were significantly lower than those of non-anesthesized rats. The learning/memory-impaired rats showed a long-lasting increased glutamate level from 24 h after isoflurane exposure to the end of the study, but the other 22 isoflurane-exposed rats did not. The learning/memory-impaired subgroup displayed a significantly higher GLAST level than the other three subgroups (p = 0.026, 0.02 and 0.032 respectively). The expression levels of GLT-1, NMDAR1, NMDAR2A/B and AMPAR of every subgroup were comparable. We found a continuous raised hippocampal glutamate and an up-regulation of GLAST rather than GLT-1, NMDAR1, NMDAR2A/B, AMPAR or tau in hippocampus of aged rats associated with isoflurane-induced learning/memory impairment.