The effect of intraoperative intermittent pneumatic compression on deep venous thrombosis prophylaxis in patients undergoing elective craniotomy.

Objective: Postoperative deep venous thrombosis (DVT) is commonly observed in patients undergoing craniotomy and is associated with a high incidence of pulmonary embolism and poor clinical outcomes. Herein, we investigated the prophylactic effect of DVT of intraoperative intermittent pneumatic compression (IPC) in patients undergoing craniotomy. Methods: A total of 516 patients who underwent elective craniotomy between December 2021 and December 2022 were enrolled in this study. Patients were randomly assigned to the intervention group (received intraoperative IPC) or control group (without IPC). Lower extremity ultrasound was performed on both legs before and after surgery (1 h, 24 h, and 7 days post-intervention). DVT was defined as the visualization of a thrombus within the vein lumen of the leg. Coagulation and platelet function were measured at the start and end of the craniotomy. Results: A total of 504 patients (251 in the intervention group and 253 in the control group) completed the study. Among these patients, 20.4% (103/504) developed postoperative DVT within the first week after surgery, with 16.7% occurring within 24 h. The incidence of postoperative DVT in the intervention group (9.6%, 24/251) was significantly lower than that in the control group (22.9%, 58/253, p < 0.001). Intraoperative IPC reduced the risk of DVT by 64.6% (0.354, 95% CI, 0.223-0.564, p < 0.001). There was no significant difference in coagulation and platelet function between the two groups (all p > 0.05). Conclusion: DVT may develop within 24 h after the craniotomy. Intraoperative application of IPC reduces the incidence of postoperative DVT.

Decompressive craniectomy for patients with malignant infarction of the middle cerebral artery: A pooled analysis of two randomized controlled trials.

BACKGROUND: Decompressive craniectomy (DC) reduces mortality without increasing the risk of very severe disability among patients with life-threatening massive cerebral infarction. However, its efficacy was demonstrated before the era of endovascular thrombectomy trials. It remains uncertain whether DC improves the prognosis of patients with malignant middle cerebral artery (MCA) infarction receiving endovascular therapy. METHODS: We pooled data from two trials (DEVT and RESCUE BT studies in China) and patients with malignant MCA infarction were included to assess outcomes and heterogeneity of DC therapy effect. Patients with herniation were dichotomized into DC and conservative groups according to their treatment strategy. The primary outcome was the rate of mortality at 90 days. Secondary outcomes included disability level at 90 days as measured by the modified Rankin Scale score (mRS) and quality-of-life score. The associations of DC with clinical outcomes were performed using multivariable logistic regression. RESULTS: Of 98 patients with herniation, 37 received DC surgery and 61 received conservative treatment. The median (interquartile range) was 70 (62-76) years and 40.8% of the patients were women. The mortality rate at 90 days was 59.5% in the DC group compared with 85.2% in the conservative group (adjusted odds ratio, 0.31 [95% confidence interval (CI), 0.10-0.94]; P=0.04). There were 21.6% of patients in the DC group and 6.6% in the conservative group who had a mRS score of 4 (moderately severe disability); and 10.8% and 4.9%, respectively, had a score of 5 (severe disability). The quality-of-life score was higher in the DC group (0.00 [0.00-0.14] vs 0.00 [0.00-0.00], P=0.004), but DC treatment was not associated with better quality-of-life score in multivariable analyses (adjusted ß Coefficient, 0.02 [95% CI, -0.08-0.11]; p=0.75). CONCLUSIONS: DC was associated with decreased mortality among patients with malignant MCA infarction who received endovascular therapy. The majority of survivors remained moderately severe disability and required improvement on quality of life. CLINICAL TRIAL REGISTRATION: The DEVT trial: http://www.chictr.org. Identifier, ChiCTR-IOR-17013568. The RESCUE BT trial: URL: http://www.chictr.org. Identifier, ChiCTR-INR-17014167.

The performance of a new type accelerator uRT-linac 506c evaluated by a quality assurance automation system.

PURPOSE: The purpose of this study was to evaluate the performance of our quality assurance (QA) automation system and to evaluate the machine performance of a new type linear accelerator uRT-linac 506c within 6 months using this system. METHODS: This QA automation system consists of a hollow cylindrical phantom with 18 steel balls in the phantom surface and an analysis software to process electronic portal imaging device (EPID) measurement image data and report the results. The performance of the QA automation system was evaluated by the tests of repeatability, archivable precision, detectability of introduced errors, and the impact of set-up errors on QA results. The performance of this linac was evaluated by 31 items using this QA system over 6 months. RESULTS: This QA system was able to automatically deliver QA plan, EPID image acquisition, and automatic analysis. All images acquiring and analysis took approximately 4.6 min per energy. The preset error of 0.1 mm in multi-leaf collimator (MLC) leaf were detected as 0.12 ± 0.01 mm for Bank A and 0.10 ± 0.01 mm in Bank B. The 2 mm setup error was detected as -1.95 ± 0.01 mm, -2.02 ± 0.01 mm, 2.01 ± 0.01 mm for X, Y, Z directions, respectively. And data from the tests of repeatability and detectability of introduced errors showed the standard deviation were all within 0.1 mm and 0.1°. and data of the machine performance were all within the tolerance specified by AAPM TG-142. CONCLUSIONS: The QA automation system has high precision and good performance, and it can improve the QA efficiency. The performance of the new accelerator has also performed very well during the testing period.

Impact of Preoperative Sleep Disturbances on Postoperative Delirium in Patients with Intracranial Tumors: A Prospective, Observational, Cohort Study.

Background: Postoperative delirium (POD) is prevalent in craniotomy patients and is associated with high mortality. Sleep disturbances are receiving increasing attention from clinicians as associated risk factors for postoperative complications. This study aimed to determine the impact of preoperative sleep disturbances on POD in craniotomy patients. Methods: We recruited 130 patients undergoing elective craniotomy for intracranial tumors between May 1st and December 30th, 2022. Preoperative subjective sleep disturbances were assessed using the Pittsburgh Sleep Quality Index on the day of admission. We also measured objective perioperative sleep patterns using a dedicated sleep monitoring device 3 days before and 3 days after the surgery. POD was assessed twice daily using the Confusion Assessment Model for the Intensive Care Unit within the first week after craniotomy. Results: Preoperative sleep disturbances were diagnosed in 49% of the study patients, and POD was diagnosed in 22% of all the study patients. Sleep disturbances were an independent risk factor for POD (OR: 2.709, 95% CI: 1.020-7.192, P = 0.045). Other risk factors for POD were age (OR: 3.038, 95% CI: 1.195-7.719, P = 0.020) and the duration of urinary catheterization (OR: 1.246, 95% CI: 1.025-1.513, P = 0.027). Perioperative sleep patterns (including sleep latency, deep sleep duration, frequency of awakenings, apnea-hypopnea index, and sleep efficiency) were significantly associated with POD. Conclusion: This study demonstrated that preoperative sleep disturbances predispose patients undergoing craniotomy to POD, also inferred a correlation between perioperative sleep patterns and POD. The targeted screening and intervention specifically for sleep disturbances during the perioperative period are immensely required.

Metal artifacts reduction in kV-CT images with polymetallic dentures and complex metals based on MV-CBCT images in radiotherapy.

This paper proposes a metal artifact reduction method of using MV-CBCT images to correct metal artifacts in kV-CT images, especially for the complex metal artifacts caused by multi-metal interaction of patients with head and neck tumors. The different tissue regions are segmented in the MV-CBCT images to obtain template images and the metal region is segmented in the kV-CT images. Forward projection is performed to get sinogram of the template images, kV-CT images and metal region images. Artifact images can be reconstructed through those sonograms. Corrected images is generated by subtracting the artifact images from the original kV-CT images. After the first correction, the template images are generated again and brought into the previous step for iteration to get better correction result. CT data set of 7 patients are used in this study, compared with linear interpolation metal artifact (LIMAR) and normalized metal artifact reduction method, mean relative error of CT value is reduced by 50.5% and 63.3%, noise is reduced by 56.2% and 58.9%. The Identifiability Score of the tooth, upper/lower jaw, tongue, lips, masseter muscle and cavity in the corrected images by the proposed method have significantly improved (P < 0.05) than original images. The artifacts correction method proposed in this paper can effectively remove the metal artifacts in the images and greatly improve the CT value accuracy, especially in the case of multi-metal and complex metal implantation.

Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway

Purpose: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nickend labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. Results: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Conclusion: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Corrigendum: m6A regulatory gene-mediated methylation modification in glioma survival prediction.

[This corrects the article DOI: 10.3389/fgene.2022.873764.].

m6A Regulatory Gene-Mediated Methylation Modification in Glioma Survival Prediction.

The median survival of patients with gliomas is relatively short. To investigate the epigenetic mechanisms associated with poor survival, we analyzed publicly available datasets from patients with glioma. This analysis revealed 12 prognosis-related m6A regulatory genes that may be responsible for poor prognosis. These genes may be involved in genomic changes inherent to oxidative phosphorylation, adipogenesis, hedgehog signaling, and Myc signaling. We reconstructed a risk model with univariate and multivariate Cox analyses and identified older age and the m6A risk score as independent risk factors for predicting the prognosis of glioma patients, which is associated with glioma immune infiltration. In conclusion, m6A regulatory genes may serve as both reliable biomarkers and potential targets to increase the chance of survival of patients with glioma.

Unfavourable intrauterine environment contributes to abnormal gut microbiome and metabolome in twins.

OBJECTIVE: Fetal growth restriction (FGR) is a devastating pregnancy complication that increases the risk of perinatal mortality and morbidity. This study aims to determine the combined and relative effects of genetic and intrauterine environments on neonatal microbial communities and to explore selective FGR-induced gut microbiota disruption, metabolic profile disturbances and possible outcomes. DESIGN: We profiled and compared the gut microbial colonisation of 150 pairs of twin neonates who were classified into four groups based on their chorionicity and discordance of fetal birth weight. Gut microbiota dysbiosis and faecal metabolic alterations were determined by 16S ribosomal RNA and metagenomic sequencing and metabolomics, and the long-term effects were explored by surveys of physical and neurocognitive development conducted after 2~3 years of follow-up. RESULTS: Adverse intrauterine environmental factors related to selective FGR dominate genetics in their effects of elevating bacterial diversity and altering the composition of early-life gut microbiota, and this effect is positively related to the severity of selective FGR in twins. The influence of genetic factors on gut microbes diminishes in the context of selective FGR. Gut microbiota dysbiosis in twin neonates with selective FGR and faecal metabolic alterations features decreased abundances of Enterococcus and Acinetobacter and downregulated methionine and cysteine levels. Correlation analysis indicates that the faecal cysteine level in early life is positively correlated with the physical and neurocognitive development of infants. CONCLUSION: Dysbiotic microbiota profiles and pronounced metabolic alterations are associated with selective FGR affected by adverse intrauterine environments, emphasising the possible effects of dysbiosis on long-term neurobehavioural development.

BODIPY-Appended Pt(II) Complexes with High Toxicities and Anti-chemoresistance Performances in a Cisplatin Resistant In Vivo Model.

Two novel fluorophore (BODIPY)-bearing complexes, pyriplatin (mCBP) and pyrimidine-chelated cisplatin (dCBP), were synthesized and characterized. The additional BODIPY-pyridine/pyridimine motifs of the two Pt(II) complexes resulted in stronger interactions with DNA in comparison with those of cisplatin. mCBP and cisplatin caused relative decreases in life span and body length in a cisplatin resistant in vivo model, N2 (wild-type) Caenorhabditis elegans. In contrast, dCBP resulted in a dramatic reduction in the two physiological parameters in N2 C. elegans, indicating high toxicity and sensitivity. The resistance factors (RF) of cisplatin, mCBP, and dCBP were determined to be 2.46, 1.04, and 0.91, respectively. The increasing RF folds for mCBP and dCBP against cisplatin were 2.36 and 2.70, respectively. This suggested they were featured with improved anti-chemoresistance capabilities. It is noteworthy that dCBP showed lowest lethal concentration (LC50) values of 0.56 and 0.61 mM in cisplatin resistant and sensitive in vivo models, respectively. Upregulation of several evolutionary conservation genes that regulate cisplatin chemoresistance through cisplatin effluxing, the DNA damage response, the unfolded protein response, and detoxification (asna-1, parp-1, enpl-1, and skn-1) was observed upon exposure to cisplatin but not to mCBP and dCBP. This could explain the improved anti-chemoresistance performances of synthesized Pt(II) complexes.

Giant aneurysm of the bilateral vertebrobasilar junction treated by pipeline and coils: A case report and literature review.

Giant aneurysm of the posterior circulation is associated with a higher risk of rupture compared with that of the anterior circulation. Furthermore, surgical clipping and interventional embolization for giant aneurysm of the posterior circulation are more difficult and complex to perform. The present study reported on the case of a 26-year-old female who exhibited a giant spherical aneurysm of the vertebrobasilar junction (VBJ) with a maximum diameter of ~35 mm that caused cervical discomfort. In addition, the patient experienced symptoms including left-sided walking and hoarseness caused by the compression of the brainstem and the posterior cranial nerves. The risks associated with performing surgery in this area are high and the prognosis is mainly poor. The patient of the present study was treated using the Pipeline Flex device with coil embolization. As a giant aneurysm of the VBJ simultaneously affects the bilateral vertebral arteries (VAs) and basilar artery, it is a unique condition and the treatment strategy must be personalized. Based on an analysis of the hemodynamic influence on the aneurysm in the present case, the Pipeline was placed through the left VA, the coils were packed through the right VA, and finally, the right VA was proximally occluded. At 7 months after embolization, the patient's modified Rankin scale score was 1 point. Upon analysis of the hemodynamic influence on the aneurysm of the VBJ, the VA with the larger shear force on the wall of the aneurysm was selected for occlusion to simplify the treatment of the aneurysm and to maximize the probability to achieve recovery.

The Association Between Cadmium Exposure and Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

OBJECTIVE: Several studies have evaluated the association of cadmium exposure with the risk of gestational diabetes mellitus (GDM). However, the findings among these studies have been inconsistent. To further investigate the relationship, we carried out a meta-analysis to clarify the relationship between cadmium exposure and GDM risk. METHODS: Five databases (Scopus, PubMed, Web of Science, Cochrane, and CNKI) were searched for eligible studies until September 09, 2021. The quality of eligible studies was evaluated using the Newcastle-Ottawa quality assessment scale (NOS). The summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by random-effects models due to high heterogeneity. Sensitivity analysis was performed to explore the robustness of the results. Publication bias was evaluated by Egger's test and Begg's test. We also conducted meta-regression analysis and subgroup analysis to assess the potential sources of heterogeneity. RESULTS: A total of 10 studies with 32,000 participants related to our issue were included. Comparing the highest vs. lowest categories of cadmium exposure, no significant association was observed between cadmium exposure and the risk of GDM (OR = 1.16, 95% CI = 0.92-1.46, and P = 0.206). No publication bias was found in Begg's and Egger's tests (all P > 0.05). Meta-regression suggested that publication year was the potentially heterogeneous source (P = 0.034). Subgroup analysis of publication year showed that the OR of studies before the year of 2016 was 4.05 (95% CI = 1.87-8.76, P < 0.001), and prospective cohort studies showed a borderline increased GDM risk (OR = 1.15, 95% CI = 0.99-1.33, and P = 0.061). CONCLUSION: Our results indicated no significant association between cadmium exposure and GDM risk. Further high-quality prospective studies, especially those using standard analytic methods for cadmium exposure, are warranted to confirm the results.

Receptor tyrosine kinases-instructed release of its inhibitor from hydrogel to delay ovarian aging.

Premature ovarian failure (POF) is the most frequently occurred disease in ovary. Direct inhibition of mammalian target of rapamycin (mTOR) activity can treat woman POF but brings adverse effects to women. Herein, by rational design of a hydrogelator Nap-Phe-Phe-Asp-Arg-Leu-Tyr-OH (Y) and co-assembling Y with an inhibitor of receptor tyrosine kinase (RTK, an upstream kinase of mTOR), Ala-Glu-Ala-Ala-Leu-Tyr-Lys-Asn-Leu-Leu-His-Ser-OH (Inh), to form hydrogel Gel Y + Inh, we develop a "smart" strategy of RTK-responsive disassembly of the hydrogel to release Inh. Release of Inh moderately inhibits the activity of mTOR and therefore delays ovarian aging. Oocyte and zygote experiments show that Gel Y + Inh improves both meiotic maturation of the oocytes and early embryonic development of the zygotes. In vivo animal experiments indicate that Gel Y + Inh effectively delays ovarian aging in aged mice by down regulation of mTOR activity, stimulation of ovaries to secrete estrogen and progesterone, and development of more antral follicles for reproduction. We expect that our new hydrogel Gel Y + Inh could be applied to treat woman POF, as well as delay ovarian aging, in clinic in the near future.

Efficacy and safety of rescue stenting following failed mechanical thrombectomy for anterior circulation large vessel occlusion: propensity score analysis.

PURPOSE: To evaluate the effectiveness and safety of rescue stenting (RS) after failed mechanical thrombectomy (MT) for patients with large artery occlusion in the anterior circulation. METHODS: Consecutive patients who experienced failed reperfusion and subsequently did or did not undergo RS at 16 comprehensive stroke centers were enrolled from January 2015 to June 2018. Propensity score matching was used to achieve baseline balance between the patient groups. Symptomatic intracranial hemorrhage (sICH) at 48 hours and the modified Rankin Scale scores and mortality at 3 months in the two groups were compared. RESULTS: A total of 90 patients with RS and 117 patients without RS after failed MT were enrolled. Propensity score matching analysis selected 132 matched patients. The good outcome rate was significantly higher in matched patients with RS than in those without RS (36.4% vs 19.7%, p=0.033), whereas the sICH (13.6% vs 21.2%, p=0.251) and mortality (31.9% vs 43.9%, p=0.151) were not significantly different between the groups. CONCLUSIONS: RS seems to be an effective safe choice for patients with large vessel occlusion of the anterior circulation who underwent failed MT.

Infections under Skin Flap After Cranioplasty and a Simple Effective Treatment.

AIM: To report treatment experiences with titanium mesh cranioplasty infection at a single institution over the last 5 years. MATERIAL AND METHODS: We retrospectively reviewed 11 consecutive patients who were diagnosed with infection under the skin flap after titanium mesh cranioplasty and received our new treatment between Feb 2008 and Feb 2013. We performed a 2- to 6-year follow-up to evaluate prognosis and security. RESULTS: All 11 patients were cured and discharged, and all saved their infected bone flap (titanium mesh) completely. There was no recurrence of infection after follow-up for 2-6 years. CONCLUSION: Sensitive antibiotics combined with enclosed continuous irrigation and drainage is a safe, easy, economical and effective treatment for infection after titanium mesh cranioplasty that can save the infected bone flap.

The Value of Managing Severe Traumatic Brain Injury During the Perioperative Period Using Intracranial Pressure Monitoring.

This study aimed to investigate the clinical efficacy of intracranial pressure (ICP) monitoring regarding the perioperative management of patients with severe traumatic brain injury (sTBI). This was a cohort study performed between Jan 2013 and Jan 2016 and included all patients with sTBI. All patients were split into ICP monitoring and non-ICP monitoring groups. The primary outcomes were in-hospital mortality and Glasgow Outcome Scale (GOS) scores 6 months after injury, whereas the secondary outcomes include rate of successful nonsurgical treatment, rate of decompression craniotomy (DC), the length of stay in the ICU, and the hospital and medical expenses. This retrospective analysis included 246 ICP monitoring sTBI patients and 695 without ICP monitoring sTBI patients. No significant difference between groups regarding patient demographics. All patients underwent a GOS assessment 6 months after surgery. Compared to the non-ICP monitoring group, a lower in-hospital mortality (20.3% vs 30.2%, P < 0.01) and better GOS scores after 6 months (3.3 ±â€Š1.6 vs 2.9 ±â€Š1.6, P < 0.05) with ICP monitoring. In addition, patients in the ICP monitoring group had a lower craniotomy rate (41.1% vs 50.9%, P < 0.01) and a lower DC rate (41.6% vs 55.9%, P < 0.05) than those in the non-ICP monitoring group. ICU length of stay (12.4 ±â€Š4.0 days vs 10.2 ±â€Š4.8 days, P < 0.01) was shorter in the non-ICP monitoring group, but it had no difference between 2 groups on total length of hospital stay (22.9 ±â€Š13.6 days vs 24.6 ±â€Š13.6 days, P = 0.108); Furthermore, the medical expenses were significantly higher in the non-ICP monitoring group than the ICP monitoring group (11.5 ±â€Š7.2 vs 13.3 ±â€Š9.1, P < 0.01). Intracranial pressure monitoring has beneficial effects for sTBI during the perioperative period. It can reduce the in-hospital mortality and DC rate and also can improve the 6-month outcomes. However, this was a single institution and observational study, well-designed, multicenter, randomized control trials are needed to evaluate the effects of ICP monitoring for perioperative sTBI patients.

CircRNA hsa-circ-0014359 promotes glioma progression by regulating miR-153/PI3K signaling.

RNA back splicing produces circRNA, a new type of non-coding RNA. Studies have indicated that circRNAs play important roles in malignant tumors of the central nervous system. Here, we aimed to evaluate the expression of the circRNA, hsa-circ-0014359 (circ-0014359) in human glioma cell lines to assess its function in glioma progression and prognosis. The expression of circ-0014359 was increased in T98G and SHG44 cancer cell lines and glioma tissues from patients, when compared with control cells and tissue. SiRNA-mediated silencing of circ-0014359 potently inhibited cell viability, migration, invasion, and apoptosis of glioma cells. Further, our observations indicated that circ-0014359 acted as a miRNA-153 (miR-153) sponge in glioma cells. Transfection of miR-153 inhibitor significantly suppressed si-circ-0014359-induced inhibition of cell viability, cell migration, and invasion. The increased expression of circ-0014359 levels in glioma cells was correlated with downregulated expression of miR-153. Overexpression of miR-153 reduced p-AKTser473 (a PI3K pathway indicator) and the rescue experiment showed enhanced p-AKTser473 expression. Together, our study suggests that circ-0014359 promotes glioma progression via targeting miR-153/PI3K signaling pathway. Thus, our study provides insights into glioma progression and reveals potential new targets for treatment of glioma.

Early Second-Trimester Peptidomic Identification of Serum Peptides for Potential Prediction of Gestational Diabetes Mellitus.

BACKGROUND/AIMS: Early screening and diagnosis is important for minimizing gestational adverse outcomes. Routine screening of gestational diabetes mellitus (GDM) at 24-28 weeks with 75 g oral glucose challenge test (OGCT) leaves limited time for intervention and prevention. This study aims to analyze maternal serum peptides in the early second-trimester for prediction of gestational diabetes mellitus (GDM). METHODS: Serum samples were collected from 16-18-week pregnant women that visited Nanjing Maternity and Child Health Care Hospital from April to August 2015. According to gestational outcome with or without GDM in late pregnancy, 200 of serum samples from GDM mothers and controls were randomly divided into two subgroups. Peptidomic identification of serum peptides was performed by combining ultrafiltration and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate the differentially-expressed peptides between two groups. RESULTS: A total of 297 identified peptides, originating from 228 proteins, were significantly differentially expressed in the GDM group compared with control. These precursor proteins may play critical roles in cell death of cortical neurons, elongation of cellular protrusions, and stabilization of microtubules. Major networks identified included those involving lipid metabolism, molecular transport and small molecule biochemistry. CONCLUSION: We provide for the first time a validated peptidome profile of early second-trimester serum in normal and GDM mothers, and we investigated the potential serum biomarkers for GDM. We concluded that 297 peptides could serve as potential biomarkers for GDM.

Positive End-Expiratory Pressure Ventilation Induces Longitudinal Atrophy in Diaphragm Fibers.

RATIONALE: Diaphragm weakness in critically ill patients prolongs ventilator dependency and duration of hospital stay and increases mortality and healthcare costs. The mechanisms underlying diaphragm weakness include cross-sectional fiber atrophy and contractile protein dysfunction, but whether additional mechanisms are at play is unknown. OBJECTIVES: To test the hypothesis that mechanical ventilation with positive end-expiratory pressure (PEEP) induces longitudinal atrophy by displacing the diaphragm in the caudal direction and reducing the length of fibers. METHODS: We studied structure and function of diaphragm fibers of mechanically ventilated critically ill patients and mechanically ventilated rats with normal and increased titin compliance. MEASUREMENTS AND MAIN RESULTS: PEEP causes a caudal movement of the diaphragm, both in critically ill patients and in rats, and this caudal movement reduces fiber length. Diaphragm fibers of 18-hour mechanically ventilated rats (PEEP of 2.5 cm H2O) adapt to the reduced length by absorbing serially linked sarcomeres, the smallest contractile units in muscle (i.e., longitudinal atrophy). Increasing the compliance of titin molecules reduces longitudinal atrophy. CONCLUSIONS: Mechanical ventilation with PEEP results in longitudinal atrophy of diaphragm fibers, a response that is modulated by the elasticity of the giant sarcomeric protein titin. We postulate that longitudinal atrophy, in concert with the aforementioned cross-sectional atrophy, hampers spontaneous breathing trials in critically ill patients: during these efforts, end-expiratory lung volume is reduced, and the shortened diaphragm fibers are stretched to excessive sarcomere lengths. At these lengths, muscle fibers generate less force, and diaphragm weakness ensues.

Use of esophageal balloon pressure-volume curve analysis to determine esophageal wall elastance and calibrate raw esophageal pressure: a bench experiment and clinical study.

BACKGROUND: Accurate measurement of esophageal pressure (Pes) depends on proper filling of the balloon. Esophageal wall elastance (Ees) may also influence the measurement. We examined the estimation of balloon-surrounding elastance in a bench model and investigated a simplified calibrating procedure of Pes in a balloon with relatively small volume. METHODS: The Cooper balloon catheter (geometric volume of 2.8 ml) was used in the present study. The balloon was progressively inflated in different gas-tight glass chambers with different inner volumes. Chamber elastance was measured by the fitting of chamber pressure and balloon volume. Balloon pressure-volume (P-V) curves were obtained, and the slope of the intermediate linear section was defined as the estimated chamber elastance. Balloon volume tests were also performed in 40 patients under controlled ventilation. The slope of the intermediate linear section on the end-expiratory esophageal P-V curve was calculated as the Ees. The balloon volume with the largest Pes tidal swing was defined as the best volume. Pressure generated by the esophageal wall during balloon inflation (Pew) was estimated as the product of Ees and best volume. Because the clinical intermediate linear section enclosed filling volume of 0.6 to 1.4 ml in each of the patient, we simplified the estimation of Ees by only using parameters at these two filling volumes. RESULTS: In the bench experiment, bias (lower and upper limits of agreement) was 0.5 (0.2 to 0.8) cmH2O/ml between the estimated and measured chamber elastance. The intermediate linear section on the clinical and bench P-V curves resembled each other. Median (interquartile range) Ees was 3.3 (2.5-4.1) cmH2O/ml. Clinical best volume was 1.0 (0.8-1.2) ml and ranged from 0.6 to 1.4 ml. Estimated Pew at the best volume was 2.8 (2.5-3.5) cmH2O with a maximum value of 5.2 cmH2O. Compared with the conventional method, bias (lower and upper limits of agreement) of Ees estimated by the simple method was - 0.1 (- 0.7 to 0.6) cmH2O/ml. CONCLUSIONS: The slope of the intermediate linear section on the balloon P-V curve correlated with the balloon-surrounding elastance. The estimation of Ees and calibration of Pes were feasible for a small-volume-balloon. TRIAL REGISTRATION: Identifier NCT02976844 . Retrospectively registered on 29 November 2016.