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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.
The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.
In this study, for the first time, we consider longitudinal motion of the walls during peristalsis in a distensible tube and how this affects backward (or retrograde) flow, i.e. peristaltic reflux. Building on the analytical model developed by Shapiro et al. (J. Fluid Mech., vol. 37, no. 4, 1969, pp. 799–825) based on lubrication theory, we model peristalsis as a two-dimensional infinite sinusoidal wavetrain. We develop an objective function with high mechanical pumping efficiency and low reflux to find optimal peristalsis conditions. We show that optimal wall longitudinal motion contributes substantially to limiting reflux during peristalsis. The results suggest that the optimal form of wall longitudinal velocity is a linear function of the wall transverse coordinate, moving forward with the wave when the tube is distended and retracting when contracted. Our results are in general agreement with clinical observations of ureteral peristalsis.
OBJECTIVES/GOALS: Childhood psychiatric symptoms are highly comorbid. Their co-occurrence and association with negative life outcomes is partially explained by deficits in executive control, or processes enabling self-regulation. Here, we test a novel executive neural target in three fMRI tasks and its relevance to shared psychopathology. METHODS/STUDY POPULATION: We studied 60 children [15 F/45 M; mean age (SD)=11.6 years (1.62)] with diverse diagnoses including attention deficit disorder (n=26) and autism spectrum disorder (n=22). We extracted a latent general factor of psychopathology using principal component analyses applied to parent-report Child Behavior Checklist syndrome scores. Subjects completed 3 executive control fMRI probes, tapping adaptive control, working memory, and inhibition. Correlational psychophysiological interaction (cPPI) analysis measured correlations between executive control-related modulations of activity in 414 network-affiliated parcels. We selected parcels exhibiting control-related cross-network correlations as well as control-related activity across all tasks and tested them for association with psychopathology. RESULTS/ANTICIPATED RESULTS: cPPI connectivity matrices were thresholded and graphs were identified using the Network-Based Statistic toolbox (p90th percentile PC) as well as control-related activation (>10% activated voxels; p DISCUSSION/SIGNIFICANCE: Our results examine cross-network interactions between brain regions during 3 fMRI tasks and their role in explaining individual variation in psychopathology. As executive control links to both comorbidity and life outcomes, identifying the clinically-relevant neural correlates of controlled behavior may lead to transdiagnostic treatments.
This study aimed to compare the pre- and post-operative vestibular and equilibrium functions of patients with cholesteatoma-induced labyrinthine fistulas who underwent different management methods.
Methods
Data from 49 patients with cholesteatoma-induced labyrinthine fistulas who underwent one of three surgical procedures were retrospectively analysed. The three management options were fistula repair, obliteration and canal occlusion.
Results
Patients underwent fistula repair (n = 8), canal occlusion (n = 18) or obliteration procedures (n = 23). Patients in the fistula repair and canal occlusion groups suffered from post-operative vertigo and imbalance, which persisted for longer than in those in the obliteration group. Despite receiving different management strategies, all patients achieved complete recovery of equilibrium functions through persistent efforts in rehabilitation exercises.
Conclusion
Complete removal of the cholesteatoma matrix overlying the fistula is reliable for preventing iatrogenic hearing deterioration due to unremitting labyrinthitis. Thus, among the three fistula treatments, obliteration is the optimal method for preserving post-operative vestibular functions.
Postpartum depression (PPD) affects up to one in five mothers and birthing parents, yet as few as 10% access evidence-based treatment. One-day cognitive behavioral therapy (CBT)-based workshops for PPD have the potential to reach large numbers of sufferers and be integrated into stepped models of care.
Methods
This randomized controlled trial of 461 mothers and birthing parents in Ontario, Canada with Edinburgh Postnatal Depression Scale (EPDS) scores ⩾10, age ⩾18 years, and an infant <12 months of age compared the effects of a 1-day CBT-based workshop plus treatment as usual (TAU; i.e. care from any provider(s) they wished) to TAU alone at 12-weeks post-intervention on PPD, anxiety, the mother–infant relationship, offspring behavior, health-related quality of life, and cost-effectiveness. Data were collected via REDCap.
Results
Workshops led to meaningful reductions in EPDS scores (m = 15.77 to 11.22; b = −4.6, p < 0.01) and were associated with three times higher odds of a clinically significant decrease in PPD [odds ratio (OR) 3.00, 95% confidence interval (CI) 1.93–4.67]. Anxiety also decreased and participants had three times the odds of clinically significant improvement (OR 3.20, 95% CI 2.03–5.04). Participants reported improvements in mother–infant bonding, infant-focused rejection and anger, and effortful control in their toddlers. The workshop plus TAU achieved similar quality-adjusted life-years at lower costs than TAU alone.
Conclusions
One-day CBT-based workshops for PPD can lead to improvements in depression, anxiety, and the mother–infant relationship and are cost-saving. This intervention could represent a perinatal-specific option that can treat larger numbers of individuals and be integrated into stepped care approaches at reasonable cost.
The spatio-temporal variation of leaf chlorophyll content is an important crop phenotypic trait that is of great significance for evaluating crop productivity. This study used a soil-plant analysis development (SPAD) chlorophyll meter for non-destructive monitoring of leaf chlorophyll dynamics to characterize the patterns of spatio-temporal variation in the nutritional status of maize (Zea mays L.) leaves under three nitrogen treatments in two cultivars. The results showed that nitrogen levels could affect the maximum leaf SPAD reading (SPADmax) and the duration of high SPAD reading. A rational model was used to measure the changes in SPAD readings over time in single leaves. This model was suitable for predicting the dynamics of the nutrient status for each leaf position under different nitrogen treatments, and model parameter values were position dependent. SPADmax at each leaf decreased with the reduction of nitrogen supply. Leaves at different positions in both cultivars responded differently to higher nitrogen rates. Lower leaves (8th–10th positions) were more sensitive than the other leaves in response to nitrogen. Monitoring the SPAD reading dynamic of lower leaves could accurately characterize and assess the nitrogen supply in plants. The lower leaves in nitrogen-deficient plants had a shorter duration of high SPAD readings compared to nitrogen-sufficient plants; this physiological mechanism should be studied further. In summary, the spatio-temporal variation of plant nitrogen status in maize was analysed to determine critical leaf positions for potentially assisting in the identification of appropriate agronomic management practices, such as the adjustment of nitrogen rates in late fertilization.
The extent of the reduction of maize (Zea mays L.) kernel moisture content through drying is closely related to field temperature (or accumulated temperature; AT) following maturation. In 2017 and 2018, we selected eight maize hybrids that are widely planted in Northeastern China to construct kernel drying prediction models for each hybrid based on kernel drying dynamics. In the traditional harvest scenario using the optimal sowing date (OSD), maize kernels underwent drying from 4th September to 5th October, with variation coefficients of 1.0–1.9. However, with a latest sowing date (LSD), drying occurred from 14th September to 31st October, with variation coefficients of 1.3–3.0. In the changed harvest scenario, the drying time of maize sown on the OSD condition was from 12th September to 9th November with variation coefficients of 1.3–3.0, while maize sown on the LSD had drying dates of 26th September to 28th October with variation coefficients of 1.5–3.6. In the future harvest scenario, the Fengken 139 (FK139) and Jingnongke 728 (JNK728) hybrids finished drying on 20th October and 8th November, respectively, when sown on the OSD and had variation coefficients of 2.7–2.8. Therefore, the maize kernel drying time was gradually delayed and was associated with an increased demand for AT ⩾ 0°C late in the growing season. Furthermore, we observed variation among different growing seasons likely due to differences in weather patterns, and that sowing dates impact variations in drying times to a greater extent than harvest scenarios.
The use of a submerged inlet is advantageous in modern aircrafts because of its low drag resistance, small radar cross section and ease of maintenance. Although it is well known that the forebody boundary layer deteriorates the aerodynamic performance of a submerged inlet, the level of impact has not yet been fully quantified. To quantify the forebody boundary-layer effect, a submerged diverter was designed to remove a portion of the low-energy boundary flow. The flow pattern and aerodynamic performance of a submerged inlet, with and without the diverter, were investigated by wind-tunnel experimentation and numerical simulations. The effects of mass flow, free stream speed, angle-of-attack and sideslip angle on the aerodynamic characteristics of the inlet with and without the submerged diverter were studied, over an operating envelope of M0 = 0.3 ∼ 0.6, $\alpha$ = –6$^{\circ}$ ∼ 8$^{\circ}$ and $\beta$ = 0$^{\circ}$ ∼ 4$^{\circ}$. The results indicate that both the total pressure loss and the circumferential distortion can be significantly reduced with the removal of the forebody boundary-layer low-energy flow. Meanwhile, the main mechanisms for losses in the submerged inlet were also analysed.
The characteristic traits of maize (Zea mays L.) leaves affect light interception and photosynthesis. Measurement or estimation of individual leaf area has been described using discontinuous equations or bell-shaped functions. However, new maize hybrids show different canopy architecture, such as leaf angle in modern maize which is more upright and ear leaf and adjacent leaves which are longer than older hybrids. The original equations and their parameters, which have been used for older maize hybrids and grown at low plant densities, will not accurately represent modern hybrids. Therefore, the aim of this paper was to develop a new empirical equation that captures vertical leaf distribution. To characterize the vertical leaf profile, we conducted a field experiment in Jilin province, Northeast China from 2015 to 2018. Our new equation for the vertical distribution of leaf profile describes leaf length, width or leaf area as a function of leaf rank, using parameters for the maximum value for leaf length, width or area, the leaf rank at which the maximum value is obtained, and the width of the curve. It thus involves one parameter less than the previously used equations. By analysing the characteristics of this new equation, we identified four key leaf ranks (4, 8, 14 and 20) for which leaf parameter values need to be quantified in order to have a good estimation of leaf length, width and area. Together, the method of leaf area estimation proposed here adds versatility for use in modern maize hybrids and simplifies the field measurements by using the four key leaf ranks to estimate vertical leaf distribution in maize canopy instead of all leaf ranks.
Bordetella bronchiseptica is a potential zoonotic pathogen, which mainly causes respiratory diseases in humans and a variety of animal species. B. bronchiseptica is one of the important pathogens isolated from rabbits in Fujian Province. However, the knowledge of the epidemiology and characteristics of the B. bronchiseptica in rabbits in Fujian Province is largely unknown. In this study, 219 B. bronchiseptica isolates recovered from lung samples of dead rabbits with respiratory diseases in Fujian Province were characterised by multi-locus sequencing typing, screening virulence genes and testing antimicrobial susceptibility. The results showed that the 219 isolates were typed into 11 sequence types (STs) including five known STs (ST6, ST10, ST12, ST14 and ST33) and six new STs (ST88, ST89, ST90, ST91, ST92 and ST93) and the ST33 (30.14%, 66/219), ST14 (26.94%, 59/219) and ST12 (16.44%, 36/219) were the three most prevalent STs. Surprisingly, all the 219 isolates carried the five virulence genes (fhaB, prn, cyaA, dnt and bteA) in the polymerase chain reaction screening. Moreover, the isolates were resistant to cefixime, ceftizoxime, cefatriaxone and ampicillin at rates of 33.33%, 31.05%, 11.87% and 3.20%, respectively. This study showed the genetic diversity of B. bronchiseptica in rabbits in Fujian Province, and the colonisation of the human-associated ST12 strain in rabbits in Fujian Province. The results might be useful for monitoring the epidemic strains, developing preventive methods and preventing the transmission of epidemic strains from rabbits to humans.
Correct diagnosis of cause of death is necessary to suggest the most effective management interventions to reduce perinatal lamb mortality. Haemorrhage on the surface of the brain has been used as a field diagnostic tool to allocate lambs to a cause of death category, but the usefulness of this method was unclear. This study aimed to evaluate whether gross pathology was related to neuronal death and whether haemorrhage of the central nervous system (CNS) was distinct between differing causes of death, enabling indicators to be used in field diagnoses. Lambs dying from natural causes (n = 64) and from euthanasia (n = 7) underwent postmortem examination, then the brain and spinal cord were extracted and examined histologically. Histological changes consistent with neuronal death were not detected in any lamb. Haemorrhage of the meninges and/or parenchyma of the CNS occurred in all lambs. The age of the haemorrhage indicated that it occurred near the time of death in most lambs. Dilation of blood vessels varied in severity but appeared to be unrelated to causal diagnosis, severity of subcutaneous oedema, breathing or milk status. Moderate or severe dilation of blood vessels and haemorrhage of the CNS did not occur in all lambs with alternative clear indicators of dystocia and occurred in all death classifications, so it could not be used as diagnostic indicators for classification of cause of death. Dilation and haemorrhage were unrelated to neuronal damage and may have been artefactual. In conclusion, haemorrhage of the CNS was not indicative of neuronal damage and could not be used to distinguish between lambs with clear indicators of differing causes of death, so it is not recommended as a field diagnostic tool.
The surface flooding of Antarctic sea ice in summer covers 50% or more of the sea-ice area in the major summer ice packs, the western Weddell and the Bellingshausen-Amundsen Seas. Two CRREL ice mass-balance buoys were deployed on the Amundsen Sea pack in late December 2010 from the icebreaker Oden, bridging the summer period (January–February 2011). Temperature records from thermistors embedded vertically in the snow and ice showed progressive increases in the depth of the flooded layer (up to 0.3–0.35 m) on the ice cover during January and February. While the snow depth was relatively unchanged from accumulation (<10 cm), ice thickness decreased by up to a meter from bottom melting during this period. Contemporaneous with the high bottom melting, under-ice water temperatures up to 1°C above the freezing point were found. The high temperature arises from solar heating of the upper mixed layer which can occur when ice concentration in the local area falls and lower albedo ocean water is exposed to radiative heating. The higher proportion of snow ice found in the Amundsen Sea pack ice therefore results from both winter snowfall and summer ice bottom melt found here that can lead to extensive surface flooding.
Innovation Concept: Research training programs for students, especially in emergency medicine (EM), may be difficult to initiate due to lack of protected time, resources, and mentors (Chang Y, Ramnanan CJ. Academic Medicine 2015). We developed a ten-week summer program for medical students aimed at cultivating research skills through mentorship, clinical enrichment, and immersion in EM research culture through shadowing and project support. Methods: Five second year Ontario medical students were recruited to participate in the Summer Training and Research in Emergency Medicine (STAR-EM) program at University Health Network, Toronto, from June - Aug, 2019. Program design followed review of existing summer research programs and literature regarding challenges to EM research (McRae, Perry, Brehaut et al. CJEM 2018). The program had broad emergency physician (EP) engagement, with five EP research project mentors, and over ten EPs delivering academic sessions. Curriculum development was collaborative and iterative. All projects were approved by the hospital Research Ethics Board (REB). Curriculum, Tool or Material: Each weekly academic morning comprised small group teaching (topics including research methodology, manuscript preparation, health equity, quality improvement, and wellness), followed by EP-led group progress review of each student's project. Each student spent one half day per week in the emergency department (ED), shadowing an EP and identifying patients for recruitment for ongoing mentor-initiated ED research projects. Remaining time was spent on independent student project work. Presentation to faculty and program evaluation occurred in week 10. Scholarly output included one abstract submitted for publication per student. Program evaluation by students reflected a uniform impression that course material and mentorship were each excellent (100%, n = 5). Interest in pursuing academic EM as a career was identified by all students. Faculty researchers rated the program as very effective (80%, n = 4) or somewhat effective (20%, n = 1) in terms of enhancing productivity and scholarly output. Conclusion: The STAR-EM program provides a transferable model for other academic departments seeking to foster the development of future clinician investigators and enhance ED research culture. Program challenges included delays in REB approval for student projects and engaging recalcitrant staff to participate in research.
Introduction: Acute bloody diarrhea obligates rapid and accurate diagnostic evaluation; few studies have described such cohorts of children. Methods: We conducted a planned secondary analysis employing the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) acute gastroenteritis study cohort to describe the characteristics of children with acute bloody diarrhea, compared to a cohort of children without hematochezia. Children <18 years of age presenting to 2 pediatric tertiary care emergency departments (EDs) in Alberta, with ≥3 episodes of diarrhea and/or vomiting in the preceding 24 hours and <7 days of symptoms were consecutively recruited. Stools were tested for 17 viruses, bacteria and parasites. Primary outcomes were clinical characteristics and pathogens identified. Secondary outcomes included interventions and resource utilization. Results: Of 2257 children enrolled between October 2015 and August 2018, hematochezia before or at the index ED visit was reported in 122 (5.4%). Compared to children with nonbloody diarrhea, children with hematochezia had longer illness duration [59.5 vs. 41.5 hrs, difference 10.6, 95% CI 3.5, 19.9], more diarrheal episodes in a 24-hour period [8 vs. 5, difference 3, 95% CI 2, 4], and less vomiting [55.7% vs. 91.1%; difference -35.3%; 95% CI -44.7, -26.3]. They received more intravenous fluids [32.0% vs. 18.3%; difference 13.7%, 95% CI 5.5, 23.0], underwent non-study stool testing [53.7% vs. 4.8%; difference 49.0%, 95% CI 39.6, 58.0], experienced longer ED visits [4.1 vs. 3.3 hours, difference 0.9, 95% CI 0.3, 1.0] and were more likely to have repeat healthcare visits within 14 days [54.8% vs. 34.2%; difference 20.6%, 95% CI 10.8, 30.1]. A bacterial enteric pathogen was found in 31.9% of children with hematochezia versus 6.6% without bloody diarrhea (difference 25.4%, 95% CI 17.2, 34.7). In children with hematochezia, the most commonly detected bacteria were Salmonella spp. (N = 15), Shiga toxin-producing E. coli (N = 9), Campylobacter spp. (N = 7), and Shigella spp. (N = 5). Viruses were detected in 32.8% of children with bloody diarrhea, most commonly adenovirus (N = 15), norovirus (N = 14), sapovirus (N = 8) and rotavirus (N = 7). Conclusion: Children with hematochezia differed clinically from those without hematochezia and required more healthcare resources. While bacterial etiologies are common, several viruses were also detected.
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.
The relative effect of the atypical antipsychotic drugs and conventional agents on neurocognition in patients with early-stage schizophrenia has not been comprehensively determined.
Aims
The present study aimed to assess the cognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions.
Objectives
In a 12 months open-label, multicenter study, 698 patients with early-stage schizophrenia (< 5 years) were monotherapy with chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine or aripiprazole. Wechsler Memory Scale--Revised Visual Reproduction Test, Wechsler Adult Intelligence Scale Revised Digit Symbol Test and Digit-span Task Test, Trail Making Tests Part A and Part B, and Wisconsin Card Sorting Test were administered at baseline and 12 months follow-up evaluation. The primary outcome was change in a cognitive composite score after 12 months of treatment.
Results
Compared with scores at baseline, the composite cognitive test scores and individual test scores had significant improvement for all seven treatment groups at 12-month follow-up evaluation (all p-values ≤ 0.013). However, olanzapine and quetiapine provided greater improvement than that provided by chlorpromazine and sulpiride in the composite score, processing speed and executive function (all p-values ≤ 0.045).
Conclusions
Both conventional and atypical antipsychotic medication long-term maintenance treatment can benefit congitive function in patients with early-stage schizophrenia, but olanzapine and quetiapine may be superior to chlorpromazine and sulpiride in improving some areas of neurocognitive function.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Methods:
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
Results:
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Conclusions:
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
The aim of this study was to develop and externally validate a simple-to-use nomogram for predicting the survival of hospitalised human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (hospitalised person living with HIV/AIDS (PLWHAs)). Hospitalised PLWHAs (n = 3724) between January 2012 and December 2014 were enrolled in the training cohort. HIV-infected inpatients (n = 1987) admitted in 2015 were included as the external-validation cohort. The least absolute shrinkage and selection operator method was used to perform data dimension reduction and select the optimal predictors. The nomogram incorporated 11 independent predictors, including occupation, antiretroviral therapy, pneumonia, tuberculosis, Talaromyces marneffei, hypertension, septicemia, anaemia, respiratory failure, hypoproteinemia and electrolyte disturbances. The Likelihood χ2 statistic of the model was 516.30 (P = 0.000). Integrated Brier Score was 0.076 and Brier scores of the nomogram at the 10-day and 20-day time points were 0.046 and 0.071, respectively. The area under the curves for receiver operating characteristic were 0.819 and 0.828, and precision-recall curves were 0.242 and 0.378 at two time points. Calibration plots and decision curve analysis in the two sets showed good performance and a high net benefit of nomogram. In conclusion, the nomogram developed in the current study has relatively high calibration and is clinically useful. It provides a convenient and useful tool for timely clinical decision-making and the risk management of hospitalised PLWHAs.