3D bioengineered neural tissue generated from patient-derived iPSCs mimics time-dependent phenotypes and transcriptional features of Alzheimer's disease.

Several iPSC-derived three-dimensional (3D) cultures have been generated to model Alzheimer's disease (AD). While some AD-related phenotypes have been identified across these cultures, none of them could recapitulate multiple AD-related hallmarks in one model. To date, the transcriptomic features of these 3D models have not been compared with those of human AD brains. However, these data are crucial to understanding the pertinency of these models for studying AD-related pathomechanisms over time. We developed a 3D bioengineered model of iPSC-derived neural tissue that combines a porous scaffold composed of silk fibroin protein with an intercalated collagen hydrogel to support the growth of neurons and glial cells into complex and functional networks for an extended time, a fundamental requisite for aging studies. Cultures were generated from iPSC lines obtained from two subjects carrying the familial AD (FAD) APP London mutation, two well-studied control lines, and an isogenic control. Cultures were analyzed at 2 and 4.5 months. At both time points, an elevated Aß42/40 ratio was detected in conditioned media from FAD cultures. However, extracellular Aß42 deposition and enhanced neuronal excitability were observed in FAD culture only at 4.5 months, suggesting that extracellular Aß deposition may trigger enhanced network activity. Remarkably, neuronal hyperexcitability has been described in AD patients early in the disease. Transcriptomic analysis revealed the deregulation of multiple gene sets in FAD samples. Such alterations were strikingly similar to those observed in human AD brains. These data provide evidence that our patient-derived FAD model develops time-dependent AD-related phenotypes and establishes a temporal relation among them. Furthermore, FAD iPSC-derived cultures recapitulate transcriptomic features of AD patients. Thus, our bioengineered neural tissue represents a unique tool to model AD in vitro over time.

Association Between QRS Characteristics in Pulseless Electrical Activity and Survival Outcome in Cardiac Arrest Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: Recent studies have shown inconsistent results regarding the association between QRS characteristics and survival outcomes in patients with cardiac arrest and pulseless electrical activity (PEA) rhythms. This meta-analysis aimed to identify the usefulness of QRS width and frequency as prognostic tools for outcomes in patients with cardiac arrest and PEA rhythm. METHODS: Extensive searches were conducted using Medline, Embase, and the Cochrane Library to find articles published from database inception to 4 June 2023. Studies that assessed the association between the QRS characteristics of cardiac arrest patients with PEA rhythm and survival outcomes were included. The Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. RESULTS: A total of 9727 patients from seven observational studies were included in this systematic review and meta-analysis. The wide QRS group (QRS ≥ 120 ms) was associated with significantly higher odds of mortality than the narrow QRS group (QRS < 120 ms) (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.11-3.11, I2 = 58%). The pooled OR for mortality was significantly higher in patients with a QRS frequency of < 60/min than in those with a QRS frequency of ≥ 60/min (OR = 1.90, 95% CI = 1.19-3.02, I2 = 65%). CONCLUSIONS: Wide QRS width or low QRS frequency is associated with increased odds of mortality in patients with PEA cardiac arrest. These findings may be beneficial to guide the disposition of cardiac arrest patients with PEA during resuscitation.

Impact of extent of resection and postoperative radiotherapy on survival outcomes in intracranial solitary fibrous tumors: a systematic review and meta-analysis.

The knowledge of optimal treatments for patients with intracranial solitary fibrous tumor (SFT) is limited, with inconclusive results from previous studies. In this study, we conducted a meta-analysis of relevant studies to identify the prognostic impact of the extent of resection (EOR) and postoperative radiotherapy (PORT) on survival outcomes of patients with intracranial SFT. We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify relevant studies published till April 2022. Progression-free survival (PFS) and overall survival (OS) were the outcomes of interest. Differences between two cohorts (gross total resection [GTR] vs. subtotal resection [STR] and PORT vs. surgery only) were estimated by calculating hazard ratios. Twenty-seven studies were selected for the meta-analysis, including data of 1348 patients (GTR, n = 819 vs. STR, n = 381 and PORT, n = 723 vs. surgery only, n = 578). Pooled hazard ratios of PFS (1, 3, 5, and 10 years) and OS (3, 5, and 10 years) revealed that the GTR cohort showed sustained superiority over the STR cohort. In addition, the PORT cohort was superior to the surgery-only cohort with respect to all PFS periods. Although the 10-year OS between the two cohorts was not statistically different, PORT showed significantly better 3- and 5-year OS than surgery only. The study findings suggest that GTR and PORT provide significant benefits for PFS and OS. Aggressive surgical resection of tumors to achieve GTR followed by PORT should be implemented as optimal treatments for all patients with intracranial SFT when feasible.

Protective Effects of Hemp (Cannabis sativa) Root Extracts against Insulin-Deficient Diabetes Mellitus In Mice.

The pharmacological potential of industrial hemp (Cannabis sativa) has been widely studied. However, the majority of studies have focused on cannabidiol, isolated from the inflorescence and leaf of the plant. In the present study, we evaluated the anti-diabetic potential of hemp root water (HWE) and ethanol extracts (HEE) in streptozotocin (STZ)-induced insulin-deficient diabetic mice. The administration of HWE and HEE ameliorated hyperglycemia and improved glucose homeostasis and islet function in STZ-treated mice (p < 0.05). HWE and HEE suppressed ß-cell apoptosis and cytokine-induced inflammatory signaling in the pancreas (p < 0.05). Moreover, HWE and HEE normalized insulin-signaling defects in skeletal muscles and apoptotic response in the liver and kidney induced by STZ (p < 0.05). Gas chromatography-mass spectrometry analysis of HWE and HEE showed possible active compounds which might be responsible for the observed anti-diabetic potential. These findings indicate the possible mechanisms by which hemp root extracts protect mice against insulin-deficient diabetes, and support the need for further studies geared towards the application of hemp root as a novel bioactive material.

Spatiotemporal processing of neural cell adhesion molecules 1 and 2 by BACE1 in vivo.

Neural cell adhesion molecules 1 (NCAM1) and 2 (NCAM2) belong to the cell adhesion molecules of the immunoglobulin superfamily and have been shown to regulate formation, maturation, and maintenance of synapses. NCAM1 and NCAM2 undergo proteolysis, but the identity of all the proteases involved and how proteolysis is used to regulate their functions are not known. We report here that NCAM1 and NCAM2 are BACE1 substrates in vivo. NCAM1 and NCAM2 overexpressed in HEK cells were both cleaved by metalloproteinases or BACE1, and NCAM2 was also processed by γ-secretase. We identified the BACE1 cleavage site of NCAM1 (at Glu 671) and NCAM2 (at Glu 663) using mass spectrometry and site-directed mutagenesis. Next, we assessed BACE1-mediated processing of NCAM1 and NCAM2 in the mouse brain during aging. NCAM1 and NCAM2 were cleaved in the olfactory bulb of BACE1+/+ but not BACE1-/- mice at postnatal day 10 (P10), 4 and 12 months of age. In the hippocampus, a BACE1-specific soluble fragment of NCAM1 (sNCAM1ß) was only detected at P10. However, we observed an accumulation of full-length NCAM1 in hippocampal synaptosomes in 4-month-old BACE1-/- mice. We also found that polysialylated NCAM1 (PSA-NCAM1) levels were increased in BACE1-/- mice at P10 and demonstrated that BACE1 cleaves both NCAM1 and PSA-NCAM1 in vitro. In contrast, we did not find evidence for BACE1-dependent NCAM2 processing in the hippocampus at any age analyzed. In summary, our data demonstrate that BACE1 differentially processes NCAM1 and NCAM2 depending on the region of brain, subcellular localization, and age in vivo.

Prognostic Effect of Underlying Chronic Kidney Disease and Renal Replacement Therapy on the Outcome of Patients after Out-of-Hospital Cardiac Arrest: A Nationwide Observational Study.

Background and Objectives: This study assessed the prognostic value of underlying chronic kidney disease (CKD) and renal replacement therapy (RRT) on the clinical outcomes from out-of-hospital cardiac arrest (OHCA). Materials and Methods: This retrospective study was conducted utilizing the population-based OHCA data of South Korea between 2008 and 2018. Adult (>18 years) OHCA patients with a medical cause of cardiac arrest were included and classified into three categories based on the underlying CKD and RRT: (1) non-CKD group; (2) CKD without RRT group; and (3) CKD with RRT group. A total of 13,682 eligible patients were included (non-CKD, 9863; CKD without RRT, 1778; CKD with RRT, 2041). From the three comparison subgroups, data with propensity score matching were extracted. The influence of CKD and RRT on patient outcomes was assessed using propensity score matching and multivariate logistic regression analyses. The primary outcome was survival at hospital discharge and the secondary outcome was a good neurological outcome at hospital discharge. Results: The two CKD groups (CKD without RRT and CKD with RRT) showed no significant difference in survival at hospital discharge compared with the non-CKD group (CKD without RRT vs. non-CKD, p > 0.05; CKD with RRT vs. non-CKD, p > 0.05). The non-CKD group had a higher chance of having good neurological outcomes than the CKD groups (non-CKD vs. CKD without RRT, p < 0.05; non-CKD vs. CKD with RRT, p < 0.05) whereas there was no significant difference between the two CKD groups (CKD without RRT vs. CKD with RRT, p > 0.05). Conclusions: Compared with patients without CKD, the underlying cause of CKD­regardless of RRT­may be linked to poor neurological outcomes. Underlying CKD and RRT had no effect on the survival at hospital discharge.

Diagnostic Accuracy of Ischemia-Modified Albumin for Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

The diagnostic usefulness of ischemia-modified albumin in acute coronary syndrome (ACS) has been questioned. The goal of this systematic review and meta-analysis was to see how accurate ischemia-modified albumin (IMA) was in diagnosing ACS in patients admitted to emergency departments (EDs). We searched for relevant literature in databases such as MEDLINE, EMBASE, and the Cochrane Library. Primary studies that reliably reported on patients with symptoms suggestive of ACS and evaluated IMA on admission to emergency departments were included. The QUADAS-2 tool was used to assess the risk of bias in the included research. A total of 4,761 patients from 19 studies were included in this systematic review. The sensitivity and specificity were 0.74 and 0.40, respectively, when the data were pooled. The area under the curve value for IMA for the diagnosis of ACS was 0.75, and the pooled diagnostic odds ratio value was 3.72. Furthermore, ACS patients with unstable angina had greater serum IMA levels than those with non-ischemic chest pain. In contrast to prior meta-analyses, our findings suggest that determining whether serum IMA levels are effective for diagnosing ACS in the emergency department is difficult. However, the accuracy of these findings cannot be ascertained due to high heterogeneity between studies.

Efficacy of Quantitative Pupillary Light Reflex for Predicting Neurological Outcomes in Patients Treated with Targeted Temperature Management after Cardiac Arrest: A Systematic Review and Meta-Analysis.

Background and objectives: This study aims to evaluate the usefulness of the quantitative pupillary light reflex as a prognostic tool for neurological outcomes in post-cardiac arrest patients treated with targeted temperature management (TTM). Material and Methods: We systematically searched MEDLINE, EMBASE, and the Cochrane Library (search date: 9 July 2021) for studies on post-cardiac arrest patients treated with TTM that had measured the percent constriction of pupillary light reflex (%PLR) with quantitative pupillometry as well as assessed the neurological outcome. For an assessment of the methodological quality of the included studies, two authors utilized the prognosis study tool independently. Results: A total of 618 patients from four studies were included in this study. Standardized mean differences (SMDs) were calculated to compare patients with good or poor neurological outcomes. A higher %PLR measured at 0-24 h after hospital admission was related to good neurological outcomes at 3 months in post-cardiac arrest patients treated with TTM (SMD 0.87; 95% confidence interval 0.70-1.05; I2 = 0%). A higher %PLR amplitude measured at 24-48 h after hospital admission was also associated with a good neurological outcome at 3 months in post-cardiac arrest patients treated with TTM, but with high heterogeneity (standardized mean difference 0.86; 95% confidence interval 0.40-1.32; I2 = 70%). The evidence supporting these findings was of poor quality. For poor neurological outcome, the prognosis accuracy of %PLR was 9.19 (pooled diagnostic odds ratio, I2 = 0%) and 0.75 (area under the curve). Conclusions: The present meta-analysis could not reveal that change of %PLR was an effective tool in predicting neurological outcomes for post-cardiac arrest patients treated with TTM owing to a paucity of included studies and the poor quality of the evidence.

Prognostic Impact of In-Hospital Use of Mechanical Cardiopulmonary Resuscitation Devices Compared with Manual Cardiopulmonary Resuscitation: A Nationwide Population-Based Observational Study in South Korea.

Background and Objectives: This study analyzed the prognostic impact of mechanical cardiopulmonary resuscitation (CPR) devices in out-of-hospital cardiac arrest (OHCA) patients, in comparison to manual CPR. Materials and Methods: This study was a nationwide population-based observational study in South Korea. Data were retrospectively collected from 142,905 OHCA patients using the South Korean Out-of-Hospital Cardiac Arrest Surveillance database. We included adult OHCA patients who received manual or mechanical CPR in the emergency room. The primary outcome was survival at discharge and the secondary outcome was sustained return of spontaneous circulation (ROSC). Statistical analysis included propensity score matching and multivariate logistic regression. Results: A total of 19,045 manual CPR and 1125 mechanical CPR cases (671 AutoPulseTM vs. 305 ThumperTM vs. 149 LUCASTM) were included. In the matched multivariate analyses, all mechanical CPR devices were associated with a lower ROSC than that of manual CPR. AutoPulseTM was associated with lower survival in the multivariate analysis after matching (aOR with 95% CI: 0.57 (0.33-0.96)), but the other mechanical CPR devices were associated with similar survival to discharge as that of manual CPR. Witnessed arrest was commonly associated with high ROSC, but the use of mechanical CPR devices and cardiac origin arrest were associated with low ROSC. Only target temperature management was the common predictor for high survival. Conclusions: The mechanical CPR devices largely led to similar survival to discharge as that of manual CPR in OHCA patients; however, the in-hospital use of the AutoPulseTM device for mechanical CPR may significantly lower survival compared to manual CPR.

Efficacy and safety of erythropoietin in patients with traumatic brain injury: A systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to evaluate the effects of erythropoietin (EPO) on mortality and neurological outcomes in patients with traumatic brain injury (TBI). MATERIALS AND METHODS: Electronic databases of studies published up to January 5, 2017 were searched to retrieve relevant investigations comparing the outcomes of EPO-treated patients and untreated patients following TBI. We calculated the relative risk (RR) of mortality, neurologic outcomes, and deep vein thrombosis (DVT) with corresponding 95% confidence interval (CI) using meta-analysis. RESULTS: Six randomized controlled clinical trials met the eligibility criteria. In total, 1041 patients were included among the studies. EPO was found to significantly reduce the occurrence of mortality (RR 0.68 [95% CI 0.50-0.95]; P = 0.02), but did not significantly reduce poor functional outcome (RR 1.22 [95% CI 0.82-1.81]; P = 0.33). There were no significant differences in the occurrence of complications, such as DVT, between the treatment groups (RR -0.02 [95% CI -0.06-0.02]; P = 0.81). CONCLUSIONS: Results of the present meta-analysis suggest that the use of EPO may prevent death following TBI without causing adverse events, such as deep vein thrombosis. However, the role of EPO in improving neurological outcome(s) remains unclear. Further well-designed, randomized controlled trials using modified protocols and involving specific patient populations are required to clarify this issue, and to verify the findings.

Nonlinear Steering Wheel Angle Control Using Self-Aligning Torque with Torque and Angle Sensors for Electrical Power Steering of Lateral Control System in Autonomous Vehicles.

The development of sensor technology enabled the use of composite sensors to measure the torque and angle of steering wheels at gradually decreasing costs while maintaining the required safety. The electric power steering (EPS) is vital to the safety of the car, therefore it is not worth sacrificing safety to save cost and the SWA control with angle sensor gradually becomes the mainstream. Existing methods to control steering wheel angle (SWA) for EPS consider the self-aligning torque as a disturbance that should be rejected. However, this torque is useful to return the SWA from an outward to the center position. Hence, we propose a nonlinear control of SWA using the self-aligning torque for EPS in the lateral control system of autonomous vehicles. The proposed method consists of a high-gain disturbance observer and a backstepping controller, where the former aims to estimate the self-aligning torque, and an auxiliary state variable prevents using the derivative of the measured signal. The nonlinear controller is designed via backstepping to bound the SWA tracking error. The self-aligning torque provides damping that can improve the controller tracking when following the same direction of the input torque on the steering wheel control. In this case, the control input can be reduced by the damping effect of the self-aligning torque. The performance of the proposed method is validated through EPS hardware-in-the-loop simulation.

Dose-related effect of statins in patients with endovascular coiling or microsurgical clipping for aneurysmal subarachnoid hemorrhage: updated study-level meta-analysis.

PURPOSE: We aimed to quantitatively assess the effects of short-term statin use on delayed ischemic neurologic deficits (DINDs) and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH) through a meta-analysis of the available evidence. METHODS: We searched the electronic databases up to April 8, 2016 to retrieve relevant studies comparing the outcomes between immediate statin-treated in statin-naïve patients and untreated patients following aneurysmal SAH. Meta-analysis was performed using Review Manager 5.3. RESULTS: Eight randomized controlled clinical trials (RCTs) and 5 observational studies involving 2148 patients met the eligibility criteria. In the RCTs, statins were found to significantly reduce the occurrence of DINDs (relative risk (RR), 0.76; 95% confidence interval (CI), 0.61-0.94; P = 0.01), but did not significantly reduce poor functional outcomes (RR, 1.01; 95% CI, 0.87-1.16; P = 0.93) or mortality (RR, 0.80; 95% CI, 0.58-1.11; P = 0.18). In observational studies, statin use was not associated with any reduction in DINDs, poor outcome, or mortality. Meta-analysis of RCTs indicated a significant reduction in DINDs and mortality in patients with high-dose statin use (RR, 0.63; 95% CI, 0.42-0.95; P = 0.03; I 2 = 0%; and RR, 0.36; 95% CI, 0.15-0.86; P = 0.02; I 2 = 0%, respectively). CONCLUSION: The present meta-analysis suggests that statin use may prevent DINDs in patients with aneurysmal SAH. Based on our findings, the role of statins in improving neurological outcome was limited. However, the risk of DINDs and mortality decreased with higher statin doses in a dose-dependent manner. Hence, further well-designed RCTs with modified protocols in specific patients are required.

Prognostic role of copeptin after traumatic brain injury: A systematic review and meta-analysis of observational studies.

PURPOSE: Copeptin, the C-terminal portion of provasopressin, has emerged as a novel prognostic marker in neurocritical care, such as in traumatic brain injury (TBI). The aim of this study was to quantitatively assess the prognostic significance of initial plasma copeptin levels in the neurological outcome and mortality after traumatic brain injury. MATERIALS AND METHODS: Six relevant studies with data from 552 patients were included in this meta-analysis. RESULTS: The plasma copeptin levels were found to be significantly higher in patients who died than in the survivors (standardized mean difference [SMD], 1.80). In the four studies reporting Glasgow outcome scale (GOS) data, patients with unfavorable outcomes had significantly higher copeptin levels than those with favorable outcomes (SMD, 1.62). The plasma copeptin level predicted mortality and unfavorable outcomes (AUC, 0.873; AUC, 0.876). CONCLUSIONS: The present meta-analysis suggests that early measurement of plasma copeptin levels can provide better prognostic information about the functional outcome and mortality in patients with TBI.

Developmental Pathways from Child Maltreatment to Adolescent Substance Use: The Roles of Posttraumatic Stress Symptoms and Mother-Child Relationships.

While many studies have identified a significant relation between child maltreatment and adolescent substance use, the developmental pathways linking this relation remain sparsely explored. The current study examines posttraumatic stress (PTS) symptoms, mother-child relationships, and internalizing and externalizing problems as potential longitudinal pathways through which child maltreatment influences adolescent substance use. Structural equation modeling was conducted on 883 adolescents drawn from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). The pathways of PTS symptoms linked physical and sexual abuse to substance use, and the pathways of mother-child relationships linked emotional abuse and neglect to substance use. None of the four types of maltreatment affected substance use via internalizing or externalizing problems. The findings suggest that intervention efforts aimed at addressing posttraumatic stress symptoms and improving mother-child relationship quality may be beneficial in reducing substance use among adolescents with child maltreatment histories.

Dietary Intervention of Artemisia and Green Tea Extracts to Rejuvenate Helicobacter pylori-Associated Chronic Atrophic Gastritis and to Prevent Tumorigenesis.

OBJECT: As nonmicrobial dietary approach is capable of controlling Helicobacter pylori infection, we evaluated the efficacy of long-term dietary administration of Artemisia and/or green tea extracts on H. pylori-initiated, high-salt-promoted chronic atrophic gastritis and gastric tumorigenesis mouse model. METHODS: Helicobacter pylori-infected and high-salt-diet-administered C57BL/6 mice were administered with Artemisia extracts (MP group) and/or green tea extracts (GT group) for 36 weeks in addition to the control group (ES group, gastroprotective drug, ecabet sodium 30 mg/kg, diet pellet). Gross and pathological gastric lesions were evaluated after 24 and 36 weeks, respectively, and their underlying molecular changes were measured in gastric homogenates. Detailed mechanisms were further evaluated in in vitro cell models. RESULTS: The erythematous and nodular changes and mucosal ulcerative and erosive lesions were noted in the control group at 24 weeks. MP, GT, MPGT, and ES groups all showed significantly ameliorated pathologic lesion compared to the control group (p < .05). After the 36 weeks, scattered nodular masses with some central ulcers and thin gastric surface were noted in the control stomach, whereas no tumorous lesion and milder atrophic changes were observed in all MP, GT, and MPGT groups except ES group (p < .05). On molecular analysis, increased expressions of COX-2, TNF-α, IL-6, lipid peroxide, and activated STAT3 relevant to H. pylori infection were significantly decreased with MPGT administration (p < .01), whereas HSP70 was significantly increased. PGDH expressions, core tumor suppressor involved in carcinogenesis, were significantly decreased with H. pylori infection (p < .05), but significantly increased in MPGT group (p < .05). Increased mucosal apoptotic index noted in the control group was significantly decreased with MP and/or GT along with significantly preserved gastric gastroprotective mediators (p < .01) such as mucins, HSP27, and HSP70. H. pylori-induced serum TNF-α and NF-κB activations were significantly decreased with MPGT administration (p < .05). CONCLUSION: Long-term dietary intake of MP and/or GT can be an effective strategy either to rejuvenate H. pylori atrophic gastritis or to suppress tumorigenesis.

Irritable bowel syndrome-specific health-related quality of life instrument: development and psychometric evaluation.

BACKGROUND: Health-related quality of life (HRQOL) is an important outcome indicator for chronic disease, and particularly in the absence of biological markers for illness, such as with irritable bowel syndrome (IBS). The aims of this study were to develop and evaluate a new IBS-specific HRQOL instrument (IBS-HR-QOL). METHODS: This methodological study comprised three steps: conceptualization of the IBS-HR-QOL, item extraction and establishment of content validity, and psychometric evaluation of the instrument with 267 IBS patients recruited from four university hospitals. RESULTS: The content validity of the developed IBS-HR-QOL was assessed by 11 experts. Exploratory and confirmatory factor analyses yielded four factors. The criterion and convergent validities of the IBS-HR-QOL were demonstrated using the Short Form-36 and the Hospital Anxiety and Depression Scale, respectively. Known-groups validity was demonstrated using a symptom-severity scale. The internal consistency reliability and test-retest reliability were satisfactory, with a Cronbach's alpha and intraclass correlation coefficient of 0.93 and 0.88, respectively. CONCLUSIONS: The IBS-HR-QOL comprises a total of 16 items. The IBS-HR-QOL demonstrated good psychometric properties. This instrument is easily comprehensible and short, rendering it feasible for use in clinical practice and research.

Proper target depth of an accelerometer-based feedback device during CPR performed on a hospital bed: a randomized simulation study.

PURPOSE: Feedback devices are used to improve chest compression (CC) quality related to survival rates in cardiac arrest. However, several studies have shown that feedback devices are not sufficiently reliable to ensure adequate CC depth on soft surfaces. Here, we determined the proper target depth of feedback (TDF) using an accelerometer during cardiopulmonary resuscitation in hospital beds. METHODS: In prospective randomized crossover study, 19 emergency physicians performed CCs for 2 minutes continuously on a manikin in 2 different beds with 3 TDFs (5, 6, and 7 cm). We measured CC depth, the proportion of accurate compression depths, CC rate, the proportion of incomplete chest decompressions, the velocity of CC (CC velocity), the proportion of time spent in CC relative to compression plus decompression (duty cycle), and the time spent in CC (CC time). RESULTS: Mean (SD) CC depths at TDF 5, 6, and 7 were 45.42 (5.79), 52.68 (4.18), and 58.47 (2.48) on one bed and 46.26 (4.49), 53.58 (3.15), and 58.74 (2.10) mm on the other bed (all P<.001), respectively. The proportions of accurate compression depths and CC velocity at TDF 5, 6, and 7 differed significantly according to TDF on both beds (all P<.001).The CC rate, CC time, and proportion of incomplete chest decompression did not differ on both beds (all P>.05). The duty cycle differed significantly on only B2. CONCLUSIONS: The target depth of the real-time feedback device should be at least 6 cm but should not exceed 7 cm for optimal CC on patients on hospital beds.

Can the new McGrath laryngoscope rival the GlideScope Ranger portable video laryngoscope? A randomized manikin study.

PURPOSE: We hypothesized that novices would be able to use the McGrath MAC (Aircraft Medical Ltd, Edinburgh, UK) equally as well as the GlideScope Ranger (Verathon, Inc, Bothell, WA) for intubation in regular simulated airways. METHODS: We performed a prospective, randomized crossover study of 39 medical students using the McGrath MAC, GlideScope Ranger, and Macintosh in a manikin with 2 normal airways. The primary outcome was the intubation time. Secondary outcomes included the success rates and the overall glottic view of the 3 laryngoscopes. RESULTS: The mean intubation times for each attempt with the McGrath MAC were 30.8 ± 16.9 seconds or less and did not differ significantly from those obtained with the GlideScope Ranger or the Macintosh in both airway scenarios (P = .18; P = .49). The mean success rates at each attempt with the McGrath MAC were 82.0% ± 38.8% or more, equal to the Macintosh and the GlideScope Ranger in both scenarios (P = .026; P = .72) except during the first intubation attempt in a normal airway (P = .008). The median grades of the glottic view visible at each intubation attempt with the McGrath Mac were Cormack-Lehane grade 1 (scenario 1: interquartile range, 1-1; scenario 2: interquartile range, 1-2), which was significantly better than the Macintosh laryngoscope in both scenarios. However, the McGrath Mac did not produce a better glottic view than the GlideScope Ranger with either scenario. CONCLUSIONS: The intubation performance of novices using the McGrath MAC was equal to their performance using the GlideScope Ranger in regular simulated airways.

Target Temperature Management Effect on the Clinical Outcome of Patients with Out-of-Hospital Cardiac Arrest Treated with Extracorporeal Cardiopulmonary Resuscitation: A Nationwide Observational Study.

This study aimed to investigate whether targeted temperature management (TTM) could enhance outcomes in patients with out-of-hospital cardiac arrest (OHCA) treated with extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest. Using a nationwide OHCA registry, adult patients with witnessed OHCA of presumed cardiac origin who underwent ECPR at the emergency department between 2008 and 2021 were included. We examined the effect of ECPR with TTM on survival and neurological outcomes at hospital discharge using propensity score matching and multivariable logistic regression compared with patients treated with ECPR without TTM. Odds ratios and 95% confidence intervals were determined. A total of 399 ECPR cases were analyzed among 380,239 patients with OHCA. Of these, 330 underwent ECPR without TTM and 69 with TTM. After propensity score matching, 69 matched pairs of patients were included in the analysis. No significant differences in survival and good neurological outcomes between the two groups were observed. In the multivariable logistic regression, no significant differences were observed in survival and neurological outcomes between ECPR with and without TTM. Among the patients who underwent ECPR after OHCA, ECPR with TTM did not improve outcomes compared with ECPR without TTM.

Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease.

Recent demonstrations that the secretion, uptake, and interneuronal transfer of tau can be modulated by disease-associated tau modifications suggest that secretion may be an important element in tau-induced neurodegeneration. Here, we show that much of the tau secreted by M1C cells occurs via exosomal release, a widely characterized mechanism that mediates unconventional secretion of other aggregation-prone proteins (α-synuclein, prion protein, and ß-amyloid) in neurodegenerative disease. Exosome-associated tau is also present in human CSF samples and is phosphorylated at Thr-181 (AT270), an established phosphotau biomarker for Alzheimer disease (AD), in both M1C cells and in CSF samples from patients with mild (Braak stage 3) AD. A preliminary analysis of proteins co-purified with tau in secreted exosomes identified several that are known to be involved in disease-associated tau misprocessing. Our results suggest that exosome-mediated secretion of phosphorylated tau may play a significant role in the abnormal processing of tau and in the genesis of elevated CSF tau in early AD.