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Microvascular health is a main determinant of coronary blood flow reserve and myocardial vascular resistance. Extracardiac capillary abnormality has been reported in subjects at increased coronary heart disease risk, such as prehypertension, hypertension, diabetes, hyperlipidemia, and atherosclerosis. We have reported cardiovascular dysfunction in a cohort of maternal nutrient reduction (MNR)-induced intrauterine growth restriction (IUGR) baboon offspring. Here we test the hypothesis that there is oral capillary rarefaction associated with MNR-induced IUGR. Capillary density was quantified using in vivo high-power capillaroscopy on seven middle-aged (~10.7 yr; human equivalent ~40 yr) male IUGR baboons and seven male age-matched controls in the lateral buccal and inferior labial mucosa. While no difference was found between groups in either area by fraction area or optical density for these vascular beds derived from fetal preductal vessels, further studies are needed on post-ductal vascular beds, retina, and function.
In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.
For patients with methicillin-resistant Staphylococcus aureus (MRSA) colonization, a traditional fist-bump greeting did not significantly reduce MRSA transfer in comparison to a handshake. However, transfer was reduced with a modified fist bump that minimized the surface area of contact and when hand hygiene was performed before the handshake.
To determine the clinical significance of arachnoid cysts.
The scans of 6978 patients undergoing magnetic resonance imaging of the internal acoustic meatus for unilateral cochleovestibular symptoms were retrospectively reviewed. We identified the scans with arachnoid cysts, and assessed the statistical associations between the laterality, location and size of the arachnoid cyst, the laterality of symptoms, the patients’ age and gender.
In a total of 37 arachnoid cysts identified in 36 patients (0.5 per cent), no associations were identified between the laterality of symptoms and the laterality of the arachnoid cyst, regardless of its size or location. There were no significant associations between the location of the arachnoid cyst and the age (p = 0.99) or gender of the patient (p = 0.13), or size (p = 0.656) or side of the cyst (p = 0.61). None of the cysts with repeat imaging scans (17 cysts) demonstrated growth.
Our results suggest that most, if not all, arachnoid cysts are of no clinical significance. Given their indolent behaviour, even serial imaging is not essential.
A critical region of PTSD is the medial prefrontal cortex, which may be impaired in this disorder. Neuroimaging studies have reported reduced cortical volumes and neuronal integrity, as well as decreased function in medial prefrontal structures in this disorder.
The aim of this study is to find whether mPFC neurons have cell apoptosis, which may lead to the dysfunction of mPFC of PTSD.
The group to test apotosis was divided into SPS after1d, 4d, 7d, 14d and control group. Expression of caspase-9 and caspase-3 were detected by immunohistochemistry, immunofluorescence, western blotting and RT-PCR.
Caspase-3 was located in cytoplasm. Evaluation of Caspase-3 immunohistochemistry showed a significant increased in the SPS-1d, SPS-4d and SPS-7d compared with the normal control group, then gradually decreased in SPS-14d. Caspase-9-positive cells were expressed in the control group and the SPS groups, The positive expression was green fluorescence, which in cell body, membrane, and processes. The mRNA levels of Caspase-9 in the SPS rats were significant increased on days 1d and 4d then gradually decreased. The Caspase-3 mRNA levels peaked at SPS-7d, then decreased on SPS-14d.
The mPFC neuronal apoptosis through mintochodrial pathway would play an important role in the dysfunction of mPFC in post traumatic stress disorder patients.
The aim of this study was to reveal the possible mechanisms involved in apoptosis induced by single prolonged stress (SPS) in hippocampus of post-traumatic stress disorder (PTSD) rats.
SPS is one of the animal models proposed for PTSD. Wistar rats were killed at 1, 4, 7, 14 and 28days after exposure to SPS. Expression of caspase-9, caspase-3, cytochrome c, Bcl-2 and Bax was detected by immunohistochemistry, immunofluorescence, western blotting and electron microscopy. Apoptotic cells were assessed by TUNEL method.
Our results showed apoptotic cells were significantly increased in hippocampus of SPS rats, accompanied by release of cytochrome c from the mitochondria into the cytosol, increase of caspase-9 and caspase-3 expression and decrease of the Bcl-2 / Bax ratio.
The results indicate that SPS induced apoptosis in hippocampus of PTSD rats, and the mitochondrial pathway was involved in the process of SPS induced apoptosis. *National Natural Science Foundation of China
To compare therapeutic efficacy, social function, discontinue rate, relapse and recurrence rate of the depression outpatients with first episode between Venlafaxine extended release and Fluoxertine hydrochloride treatment. Methods In this 48 week natural parallel follow-up study, total 188 patients who meet ICD-10 criteria for a major depressive episode were admitted and assigned to receive either Venlafaxine Extended Release (Venlafaxine XR group) (n=89) or Fluoxertine hydrochloride(Fluoxertine group) (n=99).At baseline,week2,8,12,16,24,32,48,Hamilton Rating Scale for Depression (HAMD)-17 item was used to value disease severity, and Social Disability Screening Schedule(SDSS)for social disability, and the discontinue, relapse and recurrence rates were compared. Results (1) At week 24 Venlafaxine XR group had much lower HAMD17 total score than Fluoxertine group (P<0.05). (2)The remission rate and response rate between two groups had no statistical difference (P>0.05). (3) At week 12, Venlafaxine XR group had a higher SDSS score than Fluoxertine group (P<0.05).(4)At week 12, 16, 24, 32,48,Venlafaxine XR group displayed lower discontinue rates (P<0.05). Venlafaxine XR group had a longer treatment course than Fluoxertine did [(30.99±15.98) weeks vs. [(22.57±15.26) weeks] (P<0.01). (5) The relapse and recurrence rates of two groups had no statistical difference (P>0.05). Conclusions In the acute phase, Venlafaxine XR has a better effect for social function and treatment adherence than Fluoxertine hydrochloride. In the continued phase and sustained phase, Venlafaxine XR performs better for symptoms relief and treatment adherence.Venlafaxine XR has parallel performance with Fluoxertine hydrochloride by the terms of therapeutic efficacy, social function restore, relapse and recurrence rate.
There are strong links between circadian disturbance and some of the most characteristic symptoms of clinical major depressive disorder (MDD). However there are no published studies of changes in expression of clock genes or of other neuropeptides related to circadian-rhythm regulation, which may influence recurrent susceptibility after treatment with antidepressant in MDD.
Blood samples were collected from twelve healthy controls and twelve male major depressive patients pre- and post- treated with escitalopram for eight weeks at 4-hour intervals for 24 hours. Outcome measures were the relative expression of mRNA of clock genes (hPERIOD1, hPERIOD2, hPERIOD3, hCRY1, hBMAL1, hNPAS2 and hGSK-3beta) and the levels of serum melatonin, Vasoactive Intestinal Peptide (VIP), cortisol, Adrenocorticotropic Hormone (ACTH), Insulin-like Growth Factor-1(IGF-1) and growth hormone (GH) in twelve healthy controls and twelve pre- and post- treated MDD patients.
Compared with healthy controls, MDD patients showed disruptions in diurnal rhythms of expression of hPERIOD1, hPERIOD2, hCRY1, hBMAL1, hNPAS2 and hGSK-3beta, along with disruptions in diurnal rhythms of release of melatonin, VIP, cortisol, ACTH, IGF-1, and GH. Several of these disruptions (hPER1, hCRY1, melatonin, VIP, cortisol, ACTH, and IGF-1) persisted after eight weeks escitalopram treatment, as did elevation of 24-hour levels of VIP and decreases in 24-hour levels of cortisol and ACTH.
These persisted neurobiological changes may play a role in MDD symptoms that are thought to contribute to recurrence vulnerability and in maintenance therapy for a long term.
Post-traumatic stress disorder (PTSD) is a significant problem,The medial prefrontal cortex (mPFC) is known to be significantly involved in emotional adjustment.
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.
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.
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.
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.
The debates about depressive disorder and cognition impairment are supported by controversial data.
We launched the study to investigate cognitive change in first onset depressive patients over a 6 year period.
A prospective cohort was performed. Participants included 206 cases of first onset depressive Chinese outpatient aged from 17 to 60 year old and followed from Apr. 2003-Feb. 2004 to Apr. 2009-Feb. 2010 in Shanghai. During the first 48 weeks, case management service was delivered. Participants were assessed by 17-HAMD and HAMA scale at baseline, week 12, week 32, week 48, and year 6. Cognitive changes were assessed using the WMS-RC, WAIS-RC, and WCST at baseline (n = 116), week 12 (n = 80) and year 6 (n = 24), 41 normal participants as control.
(1) During the first depressive onset, cognitive performance deteriorated comparing with those of control group (P < 0.01).
(2) At week 12,effective medication could relieve symptom and improve cognition function (P < 0.05), cognitive performance compared between patient and control with no obvious difference (P > 0.05). While patient group had a significantly larger proportion (whose Memory Quotient below 85) than control group did (χ2 = 5.66, P < 0.05).
(3) Using a general linear mixed model to estimate cognitive change,patients with more severe depressive retardation and lower education had a worse short-term memory over 6 years (estimate = -1.65, SE = 0.80, P < 0.05;estimate=1.63, SE = 0.30, P < 0.01), adjusting for demographics and medical status.
The first onset depressive patient has cognitive defects. Memory does not full recovery after symptom relief. Short-term memory impairment persists over 6 years with relative factors.
Antipsychotic drugs (APDs) are the first-line pharmacological treatments for schizophrenia. Recent human studies have found that myelin integrity could be improved by APD treatment in schizophrenia patients. Previous studies indicated that regulation of oligodendrocyte development and function may be a novel target for APDs.
The aim of this current study was to examine the possible effects of the antipsychotic drugs (APDs) haloperidol (HAL), olanzapine (OLA), and quetiapine (QUE) on the development of oligodendroglial lineage cells.
CG4 cells, an oligodendrocyte progenitor cell line, were treated with various concentrations of HAL, OLA, or QUE for specific periods. The proliferation and differentiation of the CG4 cells were measured. The regulation of CG4 cell differentiation by oligodendrocyte lineage transcription factors 1 and 2 (Olig1 and Olig2) was examined.
The APDs used in this study had no effect on the proliferation of CG4 cells. The APDs elevated the expression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNP), a specific marker of oligodendrocytes, and promoted the CG4 cells to differentiate into CNP positive oligodendrocytes. QUE and OLA increased the expression of Olig1 and Olig2 whereas HAL only increased the expression of Olig2.
Our findings suggest that oligodendrocyte development is a target of HAL, OLA, and QUE and provide further evidence of the important role of oligodendrocytes in the pathophysiology and treatment of schizophrenia. They also indicate that the expression level of oligodendrocyte/myelinrelated genes could be profoundly affected by APDs.
Cognitive impairment is central to many psychiatric conditions and is a determinant factor of functioning. The evaluation of cognition is time-consuming and recourse to it limited by cost, accessibility of expertise, and, in the case of computerized batteries, equipment. The SCIP is a 15 minute paper and pencil evaluation of cognitive function which can be integrated into clinical practice. It is thus a tool which can assist in determining which patients require a more extensive evaluation and can inform the elaboration of a personalized treatment plan. Our group (Groupe Comorbidité psychiatrique et Dimensions) has validated a french translation of the SCIP and is testing the acceptability of its integration into clinical practice in selected clinical populations. We will present preliminary data regarding the use of the SCIP in adult attention deficit disorder. Forty adult patients with attention deficit disorder were invited to participate in the study. In order to maintain a sample representative of clinical practice the only exclusion criteria were inability to speak french and inability to give informed consent. Demographic characteristics were collected, and a multiaxial DSM-IV diagnosis determined by the treating physician, SCIP was administered. The time to administer the SCIP was recorded, and a qualitative questionnaire of patient impressions was completed. We will present preliminary results of this study.
The implementation of advanced multi-level modulation schemes such as quadrature phase-shift keying (QPSK) in contrast to the conventional on–off keying is crucial to further boost the terahertz (THz) communications speed. Thereby, carrier phase noise reduction in the THz range is one of the key goals that need to be urgently achieved. In this paper, the photonic-based THz sources and the phase noise problem are briefly summarized. Then, a low phase-noise photonic source based on the stimulated Brillouin scattering (SBS) optical fiber cavity is first applied for a 300-GHz-band QPSK wireless communication link. The highest data rate at forward-error-correction limited condition was 15 Gbaud utilizing the SBS-based photonic source with a small transmit power of ~ −36 dBm. Its transmission characteristics are evaluated and compared with the conventional optical frequency comb generator (OFCG)-based source at 5 Gbaud. The proposed SBS-based photonic source has been proven to offer better performances than the OFCG-based source with respect to the phase noise, optical carrier to noise ratio, and bit error rate in communications.
The motion of a neutrally buoyant spherical particle along the axis of an axisymmetric stagnation point flow at a rigid and smooth flat wall (Hiemenz–Homann flow) is investigated in the presence of low-to-moderate inertia effects. The particle dynamics is elucidated using numerical simulation. At distances large compared to the characteristic thickness of the boundary layer
the kinematic viscosity and
the strain rate of the carrying flow, the particle decelerates as it approaches the wall, due to the ambient pressure increase toward the stagnation point. In this part of the path, its velocity is nearly identical to that of the local undisturbed fluid at the position of its centre. Relative motion between the particle and fluid increases as the wall–particle gap reduces, due to wall-induced hydrodynamic interaction forces. Two distinct evolutions of the net force on the particle are observed, depending on the relative particle size,
is the particle radius and
is the Reynolds number. For
, the force decays monotonically to zero, while it undergoes a sharp rise before returning to zero for larger particles. In the latter case, the particle retains a sufficient velocity even for very small gap widths such that, under usual roughness levels, a rebounding collision would occur. The stress profiles at the particle surface are investigated to separate the various contributions to the hydrodynamic force. Theoretical predictions for near-wall viscous and inertial forces available in the creeping-flow and low-but-finite Reynolds-number limits, respectively, are used to pinpoint the origin of the dominant inertia effect that controls the particle dynamics when the particle gets very close to the wall.
To evaluate the upper airway morphology changes associated with ageing in adult Chinese patients with obstructive sleep apnoea.
A total of 124 male patients diagnosed with obstructive sleep apnoea by overnight polysomnography, who underwent upper airway computed tomography, were enrolled. The linear dimensions, cross-sectional area and volume of the upper airway region and the surrounding bony frame were measured. The association between ageing and upper airway morphology was analysed.
Soft palate length, minimum cross-sectional area of the retroglossal region, lateral dimensions at the minimum cross-sectional area of the retropalatal and retroglossal regions, nasopharyngeal volume, and average cross-sectional area of the nasopharyngeal region were found to significantly increase with ageing in all patients, while the upper airway shape flattened with ageing. The volume of the retropalatal region increased with ageing among the patients with a body mass index of less than 24 kg/m2. The volume of parapharyngeal fat pad increased with ageing among patients with a body mass index greater than 28 kg/m2.
A number of dimensional, cross-sectional and volumetric parameters of the pharynx increased with age, indicating that non-anatomical factors may play a more important role in the pathogenesis of obstructive sleep apnoea in aged patients.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
The output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors.
To test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients.
Compared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (<1.5 h) as quantified by a larger scaling exponent (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week.
Our results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.