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To evaluate the change in consumption of specific antibiotics in a neonatal intensive care unit after the implementation of an antimicrobial stewardship program (ASP).
Design:
Retrospective cohort study between January 1, 2010, and December 31,2019.
Setting:
The neonatal intensive care unit at British Columbia Women’s Hospital (Vancouver Canada), a tertiary-care center.
Patients:
Admitted neonates prescribed antibiotics.
Methods:
We implemented an ASP with an early implementation phase starting in January 2014 (period 2) and a later phase starting in January 2017 (period 3). Patient demographics were collected, including birth weight, gestational age, history of necrotizing enterocolitis (NEC), and surgical operations from existing databases. Interrupted time-series analysis was used, and comparison of antibiotic days of therapy (DOT) averages were conducted across the preimplementation period (period 1), period 2, and period 3 regarding total patients and subgroups.
Results:
We identified 4,512 infants. There was a significant decrease in DOT from 472 (95% confidence interval [CI], 431–517) in period 1 to 405 (95% CI, 367–446) in period 2 to 313 (95% CI, 280–350) in period 3. We detected a significant decrease in the use of ampicillin, aminoglycosides, cloxacillin, and linezolid but not in vancomycin or cefotaxime. Subgroup analyses of infants <1,500 g and those without NEC or surgery showed decreases in the use of cloxacillin, aminoglycosides, and linezolid.
Conclusions:
The implementation of an ASP was associated with a significant decrease in the overall DOT and use of certain antibiotics. This study presents important targets for ongoing ASP work.
This study aimed to analyse the temporal and spatial trends in the burden of anxiety disorders and major depressive disorder related to bullying victimisation on global, regional and country scales.
Methods
Data were from the 2019 Global Burden of Disease (GBD) Study. We assessed the global disability-adjusted life years (DALYs, per 100 000 population) of anxiety disorders and major depressive disorder attributable to bullying victimisation by age, sex and geographical location. The percentage changes in age-standardised rates of DALYs were used to quantify temporal trends, and the annual rate changes across 204 countries and territories were used to present spatial trends. Furthermore, we examined the relationship between the sociodemographic index (SDI) and the burden of anxiety disorders as well as major depressive disorder attributable to bullying victimisation and its spatial and temporal characteristics globally.
Results
From 1990 to 2019, the global DALY rates of anxiety disorders and major depressive disorder attributable to bullying victimisation increased by 23.31 and 26.60%, respectively, with 27.27 and 29.07% for females and 18.88 and 23.84% for males. Across the 21 GBD regions, the highest age-standardised rates of bullying victimisation-related DALYs for anxiety disorders were in North Africa and the Middle East and for major depressive disorder in High-income North America. From 1990 to 2019, the region with the largest percentage increase in the rates of DALYs was High-income North America (54.66% for anxiety disorders and 105.88% for major depressive disorder), whereas the region with the slowest growth rate or largest percentage decline was East Asia (1.71% for anxiety disorders and −25.37% for major depressive disorder). In terms of SDI, this study found overall upward trends of bullying-related mental disorders in areas regardless of the SDI levels, although there were temporary downward trends in some stages of certain areas.
Conclusions
The number and rates of DALYs of anxiety disorders and major depressive disorder attributable to bullying victimisation increased from 1990 to 2019. Effective strategies to eliminate bullying victimisation in children and adolescents are needed to reduce the burden of anxiety disorders and major depressive disorder. Considering the large variations in the burden by SDI and geographic location, future protective actions should be developed based on the specific cultural contexts, development status and regional characteristics of each country.
The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.
Previous study has identified increased antithrombin III (ATIII) in patients with major depressive disorder (MDD), supporting ATIII as a potential biomarker for depression diagnosis.
Objectives
This study aimed to reveal the alteration of ATIII after occipital repetitive transcranial magnetic stimulation (rTMS), and illuminate its power to evaluate and predict the curative effects in MDD treatment.
Methods
A total of 90 MDD patients were recruited and further intervened with rTMS in occipital for individualized, standard or sham treatment for five days. Those of 74 patients underwent entire detection, including clinical assessments, blood collection and protein measurement.
Results
After treatment, decreased ATIII were detected in both the individualized and the standard group (p=0.000 and 0.001, respectively) instead of the sham one. Especially, the reduction in ATIII in the individualized group was associated with improvements in several neuropsychological assessments. Besides, ATIII at baseline in the standard group and after the individualized rTMS showed high performance to evaluate or predict the response to the 5-day treatment (AUC=0.771, 95%CI, 0.571-0.971; AUC=0.875, 95%CI, 0.714-1.000, respectively) and the remission in follow-up (AUC=0.736, 95%CI, 0.529-0.943; AUC=0.828, 95%CI, 0.656-1.000, respectively). Furthermore, both baseline ATIII and change in ATIII involved in the prediction of 24-item Hamilton Depression Rating Scale in the follow-up study with significant predictive values (p=0.0240 and 0.0233, respectively).
Conclusions
This study detected a reduction in ATIII after occipital rTMS, further revealed the relationships between change in ATIII and therapeutic response, and ultimately provided evidence for the potential of ATIII as a biomarker for the evaluation and prediction of antidepressive effect.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The butterfly plastic zone theory based on Mohr Coulomb criterion has been widely used in coal mine production. In order to verify the universality of the theory, it is necessary to compare the distribution of plastic zone under different strength criteria. Based on the elastic-plastic mechanics, the principal stress distribution function around the circular tunnel is deduced in the paper, and the boundary and radius of the plastic zone under different strength criteria are calculated. The results show that the change laws of the plastic zone around the circular tunnel under different strength criteria has the following commonness: firstly, with the increase of the lateral pressure coefficient, the shape of the plastic zone presents the change laws of “circle ellipse butterfly”; Secondly, with the increase of the lateral pressure coefficient, the radius of the plastic zone is exponential distribution, while the characteristic value is different when the radius of the plastic zone is infinite. At same time, it shows that the butterfly plastic zone has a low sensitivity dependence on the strength criterion, no matter which strength criterion is adopted, and the butterfly plastic zone will inevitably appear in the surrounding rock mass of circular tunnel in the high deviator stress environment; The plastic zone with butterfly shape is highly sensitive to the stress change, and the small stress change may promote the expansion of the plastic zone. This result is significant for us to understand and prevent rock engineering disasters and accidents.
‘Recurrence’ of coronavirus disease 2019 (COVID-19) has triggered numerous discussions of scholars at home and abroad. A total of 44 recurrent cases of COVID-19 and 32 control cases admitted from 11 February to 29 March 2020 to Guanggu Campus of Tongji Hospital affiliated to Tongji Medical College Huazhong University of Science and Technology were enrolled in this study. All the 44 recurrent cases were classified as mild to moderate when the patients were admitted for the second time. The gender and mean age in both cases (recurrent and control) were similar. At least one concomitant disease was observed in 52.27% recurrent cases and 34.38% control cases. The most prevalent comorbidity among them was hypertension. Fever and cough being the most prevalent clinical symptoms in both cases. On comparing both the cases, recurrent cases had markedly elevated concentrations of alanine aminotransferase (ALT) (P = 0.020) and aspartate aminotransferase (AST) (P = 0.007). Moreover, subgroup analysis showed mild to moderate abnormal concentrations of ALT and AST in recurrent cases. The elevated concentrations of ALT and AST may be recognised as predictive markers for the risk of ‘recurrence’ of COVID-19, which may provide insights into the prevention and control of COVID-19 in the future.
Previous work led to the proposal that the precision feeding of a high-concentrate diet may represent a potential method with which to enhance feed efficiency (FE) when rearing dairy heifers. However, the physiological and metabolic mechanisms underlying this approach remain unclear. This study used metabolomics analysis to investigate the changes in plasma metabolites of heifers precision-fed diets containing a wide range of forage to concentrate ratios. Twenty-four half-sib Holstein heifers, with a similar body condition, were randomly assigned into four groups and precision fed with diets containing different proportions of concentrate (20%, 40%, 60% and 80% based on DM). After 28 days of feeding, blood samples were collected 6 h after morning feeding and gas chromatography time-of-flight/MS was used to analyze the plasma samples. Parameters of oxidative status were also determined in the plasma. The FE (after being corrected for gut fill) increased linearly (P < 0.01) with increasing level of dietary concentrate. Significant changes were identified for 38 different metabolites in the plasma of heifers fed different dietary forage to concentrate ratios. The main pathways showing alterations were clustered into those relating to carbohydrate and amino acid metabolism; all of which have been previously associated with FE changes in ruminants. Heifers fed with a high-concentrate diet had higher (P < 0.01) plasma total antioxidant capacity and superoxide dismutase but lower (P ≤ 0.02) hydroxyl radical and hydrogen peroxide than heifers fed with a low-concentrate diet, which might indicate a lower plasma oxidative status in the heifers fed a high-concentrate diet. Thus, heifers fed with a high-concentrate diet had higher FE and antioxidant capacity but a lower plasma oxidative status as well as changed carbohydrate and amino acid metabolism. Our findings provide a better understanding of how forage to concentrate ratios affect FE and metabolism in the precision-fed growing heifers.
X-ray reference powder patterns and structures have been determined for a series of cobalt- and tungsten-containing cubic alkaline-earth perovskites, (BaxSr1–x)2CoWO6 (x = 0.1, 0.2, 0.3, 0.5, 0.7, and 0.9). The structure of the end members of the series, Sr2CoWO6 and Ba2CoWO6, were tetragonal and cubic, respectively, agreeing with the literature data. From Rietveld refinements, it was found that when x = 0.1 and 0.2, the structure was tetragonal I4/m (a = 5.60481(6) and 5.62305(11) Å and c = 7.97989(12) and 7.9847(2) Å, respectively; Z = 2). When x > 0.2, the structure was cubic (Fm$\bar{3}$m, No. 225; Z = 4) (from x = 0.3 to 0.9, a increases from 7.98399(13) to 8.08871(10) Å). This tetragonal series of compounds exhibit the characteristics of a distorted double-perovskite structure. The bond valence sum values for the alkaline-earth (Ba, Sr) sites in all (BaxSr1−x)2CoWO6 members are greater than the ideal value of 2.0, indicating over-bonding situation, whereas for the W sites, as x increases, a change from under-bonding to slightly over-bonding situation was observed. Density functional theory calculations revealed that while Sr2CoWO6 is a semiconductor, Ba2CoWO6 and SrBaCoWO6 are half-metals. Powder X-ray diffraction patterns of this series of compounds (BaxSr1−x)2CoWO6, with x = 0.1, 0.2, 0.3, 0.5, 0.7, and 0.9, have been submitted to be included in the Powder Diffraction File.
We present a long-term seasonal tree ring cellulose oxygen isotope (δ18Oc) time series created by analyzing four segments (S1, S2, S3, and S4) per year during the period of 1951–2009 from southeastern Tibetan Plateau. This intraseasonal δ18Oc reveals the onset and mature phase of the summer monsoon precipitation in this region. Analysis indicates that the δ18Oc of S1 has the strongest correlation with precipitation during the regional monsoon onset (29–33 pentads, May 21–June 10, r = −0.69), and the δ18Oc values for S2, S3, and S4 correlate strongly with June, July, and August precipitation, respectively. Combined δ18Oc of S2, S3, and S4 shows the most robust correlation (r = −0.82) with the mature-phase monsoon precipitation (June-July-August, JJA), passing rigorous statistical tests for calibration and verification in dendroclimatology. These results demonstrate the feasibility in using long-term intraseasonal δ18Oc to reconstruct the Asian summer monsoon's intraseasonal variations.
The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3′-untranslated region of the CLDN5 locus was associated with schizophrenia (χ2 = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5′-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (χ2) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (χ2 = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.
To observe the changes of glucocorticoid receptors(GR) in the nucleus raphes magnus (NRM)neurons of PTSD-like rats.
Methods
25 male Wistar rats were randomly divided into PTSD model 1d, 4d, 7d, 14d groups and a normal group with 5 rats in each group. Rats in model groups were treated with SPS procedure to reproduce PTSD model.The changes of expression of GR in NRM of rats were detected by immunohistochemistry and PCR in each group, and image analysis and statistical analysis were performed in each group.
Results
GR was distributed in the nucleus of neurons. The expression of GR was sharply decreased on 1d, but gradually increased on 4d and 7d, then decreased on 14d. All of 4d, 7d, 14d are higher than the normal (P < 0.05).
Conclusion
The lasting dysfunction of GR in the nucleus raphes magnus (NRM) may play an important role in post-traumatic stress disorder rats.
To explore changes of Ca2+-CaM-CaMKIIα in basolateral amygdala of PTSD rats may reveal part of the pathogensis.
Methods
The SPS-method was used to set up the rat PTSD models. A total of 90 male Wistar rats were randomly divided into1d, 4d, 7d, 14d groups of SPS and normal control groups. The intracellular free calcium level in basolateral amygdala was examined by fluorescence spectrophotometer. CaM and CaMKIIα expression in basolateral amygdala were examined by immunohistochemistry, western blotting and reverse transcription-polymerase chain reaction (RT-PCR).
Results
The intracellular free calcium level reached the peak 1 day after SPS stimulation, then gradually decreased to normal level. The expression of CaM 1day after SPS is also the most and then decreased to normal level. In contrast, CaMKIIα expression showed a significant down-regulation 1day after SPS throughout and then gradually increased to normal level. This findings suggest dysfunction of Ca2+-CaM-CaMKIIα in basolateral amygdala of PTSD rats.
Conclusion
Thus, the trauma-induced enhanced anxiety appear to be associated with, and possibly caused by, changes of Ca2+-CaM-CaMKIIα in basolateral amygdala.
Accumulated studies indicate that schizophrenia patients are prone to present the type 2 diabetes symptoms, but the potential mechanisms behind their association remain unknown. Here we explored the pathogenetic association between SCZ and T2D based on pathway analysis and protein-protein interaction. To explore the pathway crosstalk, we constructed a pathway-based network including all of those significant pathways. Our results revealed that some pathways are shared by both SCZ and T2D diseases through a number of susceptibility genes. With 382 unique susceptibility proteins for SCZ and T2D, we further built a protein-protein interaction network by extracting their nearest interacting neighbours. Among 2,104 retrieved proteins, 364 of them were found simultaneously interacted with susceptibility proteins of both SCZ and T2D, and proposed as new candidate risk factors for both diseases. Moreover, some proteins were hub proteins with high connectivity and interacted with multiple proteins involved in both diseases.Some of these hub proteins are the components of our identified enriched pathways, including calcium signaling, g-secretase mediated ErbB4 signaling, adipocytokine signaling, insulin signaling, AKT signaling and type II diabetes mellitus pathways. Through the integration of multiple lines of information, we proposed that those signaling pathways, such as AKT signaling, that contain susceptibility genes for both diseases, could be the key pathways to bridge SCZ and T2D. AKT could be one of the important shared components and may play a pivotal role to link both of the pathogenetic processes. Our study provides the general pathway-based view of pathogenetic association between two diseases.
Posttraumtic stress disorder (PTSD) is an anxiety disorder caused by traumatic experience, exhibiting three major clinical symptoms: re-experience, avoidance and numbing, and hyperarousal (APA,DSM-IV, 1994). It is thought to involve a dysregulation of medial prefrontal cortex (mPFC) activity in response to fear. The mPFC plays an important role in regulating the stress response (RJ. Ursano et al, Textbook of Disaster Psychiatry). Studies have reported that the calcium signal in the brain cell of PTSD rats is disordered (BING XIAO et al, 2009). Calreticulin, helping to deal with misfolded proteins during the endoplasmic reticulum stress (ERS) response as molecular chaperone, is a calcium binding protein.In this study,detection of the expression level of calreticulin in mPFC of rats with PTSD provides experimental evidence reveled part pathogenesis of PTSD and Single prolonged stress (SPS) method as an established animal model for PTSD was used. A total of 75 male Wistar rats were divided randomly into five groups: SPS1d,SPS4d,SPS7d,SPS14d, and the control group. The calreticulin expression in mPFC was examined using immunohistochemistry, western boltting and reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry showed calreticulin widely distributed throughout the mPFC, mainly in the cytoplasm, appeared as buffy particle. Protein level of calreticulin of SPS group gradually increased and peaked at SPS 7d. The mRNA expression of calreticulin was upward trend and peaked at SPS4d. ERS induced by SPS stimulation made misfolded protein accumulation increase, which made calreticulin separate from calcium and increase to deal with misfolded protein. Then intracellular free calcium r increased, which exacerbated ERS and induced cell apoptosis. Expression change of calreticulin caused cell apoptosis, which may be closely related to changes of emotion,cognition of PTSD rats.
Post-traumatic stress disorder (PTSD) is a significant problem,The medial prefrontal cortex (mPFC) is known to be significantly involved in emotional adjustment.
Objective
To discuss the issue of post-traumatic stress disorder (PTSD) rat apoptosis-related genes Bcl-2, Bax and medial prefrontal cortex (mPFC) neuronal apoptosis, and to provide experimental evidence to reveal PTSD pathogenesis.
Methods
The single-prolonged stress(SPS) method was used to set up the rat PTSD models There were five groups after SPS 1 day 4 days 7 days 14 days groups and control group Serum corticosterone level was determined with chemiluminescence, mPFC neuronal apoptosis changes and detection of apoptotic index were detected with transmission electron microscopy, hoechst 33342 staining and in situ nick end labeling method (TUNEL) staining. Immunohistochemistry, immunofluorescence, RT-PCR and western blotting were used to detect the expressions of Bcl-2 and Bax in the medial prefrontal cortex neuronal.
Results
PTSD rat mPFC neuron cell apoptosis, the number of apoptotic cells gradually increased with time and reached a peak at 7 days after SPS stimulates. Bcl-2 expression reached a peak at 4d and Bax expression reached a peak at 7d after SPS stimulates, Bcl-2/Bax ratio transient increased and then gradually decreased, reached a lowest point in seventh days after SPS stimulates.
Conclusions
The expression of apoptosis related genes Bcl-2 and Bax increase and their ratio imbalances are likely to be one of the reasons that lead to PTSD in rat mPFC neurons apoptosis, which may provide the pathophysiology basis for PTSD.
To detect molecular chaperone calreticulin(CRT) expression on the hippocampus in the rat model of post-traumatic stress disorder(PTSD), and discuss the regulation of CRT on Ca2+ in hippocampus of PTSD rats, further provide the experiment basis for pathogenesis of memory anomaly in PTSD rats.
Methods
The single-prolonged stress(SPS) is one of the animal models was used to set up the rat PTSD models. Male Wistar rats were randomly divided into 1, 4, 7 days groups after exposure to SPS and a normal control group. The expression of CRT was detected by using immunohistochemistry, Western blotting and RT-PCR. The intracellular free calcium was examined by fluorescence spectrophotometer.
Results
The expression of CRT in the hippocampus obviously increased after SPS stimulation, and reached the peak at SPS 4d. The intracellular free calcium level in the hippocampus obviously increased, and reached the peak at SPS 1d, then gradually decreased.
Conclusions
PTSD caused endoplasmic reticulum stress(ERS), calcium overload, up-regulated expression of CRT, activation of unfolded protein response(UPR), which maybe result in cell apoptosis and maybe the pathogenesis basis on memory anomaly in PTSD rats.
The mechanism of PTSD is not fully understood until now. Previous studies showed PTSD induced endoplasmic reticulum stress (ERS). Grp 78 plays important role in ERS.
Objectives:
To explore changes of Grp78 and Ca2+-CaM-CaMKIIα in hippocampus of PTSD rats may reveal part of the pathogensis.
Methods:
The models of PTSD were created by SPS, which is an established animal model for PTSD. Wistar rats were selected for this study and randomly divided into a normal control group and SPS groups of 1d, 4d and 7d. The expression of GRP78 was examined by immunofluorescence, western blotting and RT-PCR. The intracellular free calcium level was examined by fluorescence spectrophotometer. CaM and CaMKIIα were examined by RT-PCR. Apoptosis was examined by TUNEL and TEM.
Results:
The results showed the intracellular free calcium level reached the peak 1 day after SPS stimulation, then gradually decreased to normal level. The expression of CaM 1 day after SPS is the most and then decreased. CaMKIIα expression showed a significant down-regulation 1 day after SPS throughout and then gradually increased to normal level. Grp 78 reached the peak 4 day after SPS stimulation. TUNEL-positive cells significantly more than the normal control group and peaked at 7d after SPS stimuli, then gradually decreased to normal level. Furthermore, some cells had a characteristics change, including chromatin condensation, appearance of chromatin crescents, and nucleus fragmentation.
Conclusions:
The results suggest that Grp 78 and changes of Ca2+-CaM-CaMKIIα in hippocampal might play an important role in the pathology of PTSD.