The ISR downstream target ATF4 represses long-term memory in a cell type-specific manner.

The integrated stress response (ISR), a pivotal protein homeostasis network, plays a critical role in the formation of long-term memory (LTM). The precise mechanism by which the ISR controls LTM is not well understood. Here, we report insights into how the ISR modulates the mnemonic process by using targeted deletion of the activating transcription factor 4 (ATF4), a key downstream effector of the ISR, in various neuronal and non-neuronal cell types. We found that the removal of ATF4 from forebrain excitatory neurons (but not from inhibitory neurons, cholinergic neurons, or astrocytes) enhances LTM formation. Furthermore, the deletion of ATF4 in excitatory neurons lowers the threshold for the induction of long-term potentiation, a cellular model for LTM. Transcriptomic and proteomic analyses revealed that ATF4 deletion in excitatory neurons leads to upregulation of components of oxidative phosphorylation pathways, which are critical for ATP production. Thus, we conclude that ATF4 functions as a memory repressor selectively within excitatory neurons.

Longitudinal study on the trajectory and influencing factors of cognitive dysfunction in lung transplantation patients.

INTRODUCTION: Lung transplantation is an effective method for treating end-stage lung disease. It prolongs the survival time of patients, improves the quality of life, and prevents the degree of mental disability. In particular, postoperative cognitive dysfunction (POCD) is one of the complications after lung transplantation. Despite this, longitudinal studies on the identification and heterogeneity of cognitive dysfunction subgroup trajectories in transplant patients are lacking. Therefore, our study aimed to evaluate the factors that influence POCD in lung transplant patients. METHODS: This prospective longitudinal study included patients who underwent lung transplantation at the transplant center of Wuxi People's Hospital from September 2022 to September 2023. Patients with lung transplants were evaluated at 8 days (T1), 1 month (T2), 3 months (T3), and 6 months (T4) after the operation. The general information questionnaire evaluated cognitive functions using the Montreal Cognitive Assessment (MoCA) numerical rating scale (NRS) and the digital pain assessment to obtain the POCD values. Latent category growth model (LCGM) analysis was used to identify heterogeneous POCD subgroups in the four observation periods. Univariate and logistic regression analyses were used to identify factors affecting POCD classification and independent risk factors. RESULTS: Based on clinical outcomes, 79 patients completed all four surveys, of whom 16 were lost during the follow-up period (loss rate, 16.8%). The cognitive function by MoCA NRS score was 14.18 ± 5.32 points on day 8 (T1), 22.51 ± 5.13 points at 1 month (T2), 25.44 ± 3.61 at 3 months (T3), and 27.04 ± 3.03 points at 6 months (T4) after lung transplantation, showing an increasing trend. The LCGM, used to fit the trajectory of MoCA scores, observed a heterogeneous trajectory of changes in lung transplant patients. Based on this analysis, patients could be divided into two categories: those with high risk (25,32%) and those with low risk (54,68%). The single-factor analysis identified that POCD values were affected by early postoperative rehabilitation exercise, degree of pain, intensive care unit (ICU) stay time, and donor lung cold ischemia time (all P < 0.05). Using the low-risk group as the reference class, logistic regression analysis showed that the model could correctly classify the subjects. CONCLUSION: Our 6-month observation of lung transplant patients showed that the degree of cognitive dysfunction had an overall downward trend and that patients could be divided into two trajectories of high and low risk for POCD. Early postoperative rehabilitation exercise, degree of pain, ICU stay time, and donor lung cold ischemia time were all influencing factors for POCD in lung transplant patients.

Synaptopodin is required for long-term depression at Schaffer collateral-CA1 synapses.

Synaptopodin (SP), an actin-associated protein found in telencephalic neurons, affects activity-dependant synaptic plasticity and dynamic changes of dendritic spines. While being required for long-term depression (LTD) mediated by metabotropic glutamate receptor (mGluR-LTD), little is known about its role in other forms of LTD induced by low frequency stimulation (LFS-LTD) or spike-timing dependent plasticity (STDP). Using electrophysiology in ex vivo hippocampal slices from SP-deficient mice (SPKO), we show that absence of SP is associated with a deficit of LTD at Sc-CA1 synapses induced by LFS-LTD and STDP. As LTD is known to require AMPA- receptors internalization and IP3-receptors calcium signaling, we tested by western blotting and immunochemistry if there were changes in their expression which we found to be reduced. While we were not able to induce LTD, long-term potentiation (LTP), albeit diminished in SPKO, can be recovered by using a stronger stimulation protocol. In SPKO we found no differences in NMDAR, which are the primary site of calcium signalling to induce LTP. Our study shows, for the first time, the key role of the requirement of SP to allow induction of activity-dependant LTD at Sc-CA1 synapses.

Loss of synaptopodin impairs mGluR5 and protein synthesis-dependent mGluR-LTD at CA3-CA1 synapses.

Metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) is an important form of synaptic plasticity that occurs in many regions of the central nervous system and is the underlying mechanism for several learning paradigms. In the hippocampus, mGluR-LTD is manifested by the weakening of synaptic transmission and elimination of dendritic spines. Interestingly, not all spines respond or undergo plasticity equally in response to mGluR-LTD. A subset of dendritic spines containing synaptopodin (SP), an actin-associated protein is critical for mGluR-LTD and protects spines from elimination through mGluR1 activity. The precise cellular function of SP is still enigmatic and it is still unclear how SP contributes to the functional aspect of mGluR-LTD despite its modulation of the structural plasticity. In this study, we show that the lack of SP impairs mGluR-LTD by negatively affecting the mGluR5-dependent activity. Such impairment of mGluR5 activity is accompanied by a significant decrease of surface mGluR5 level in SP knockout (SPKO) mice. Intriguingly, the remaining mGluR-LTD becomes a protein synthesis-independent process in the SPKO and is mediated instead by endocannabinoid signaling. These data indicate that the postsynaptic protein SP can regulate the locus of expression of mGluR-LTD and provide insight into our understanding of spine/synapse-specific plasticity.

Improvement of clinical wound microcirculation diagnosis using an object tracking-based laser speckle contrast imaging system.

Wound monitoring is crucial for effective healing, as nonhealing wounds can lead to tissue ulceration and necrosis. Evaluating wound recovery involves observing changes in angiogenesis. Laser speckle contrast imaging (LSCI) is vital for wound assessment due to its rapid imaging, high resolution, wide coverage, and noncontact properties. When using LSCI equipment, regions of interest (ROIs) must be delineated in lesion areas in images for quantitative analysis. However, patients with serious wounds cannot maintain constant postures because the affected areas are often associated with discomfort and pain. This leads to deviations between the drawn ROI and actual wound position when using LSCI for wound assessment, affecting the reliability of relevant assessments. To address these issues, we used the channel and spatial reliability tracker object tracking algorithm to develop an automatic ROI tracking function for LSCI systems. This algorithm is used to track and correct artificial movements in blood flow images, address the ROI position offset caused by the movement of the affected body part, increase the blood flow analysis accuracy, and improve the clinical applicability of LSCI systems. ROI tracking experiments were performed by simulating wounds, and the results showed that the intraclass correlation coefficient (ICC) ranged from 0.134 to 0.976. Furthermore, the object within the ROI affected tracking performance. Clinical assessments across wound types showed ICCs ranging from 0.798 to 0.917 for acute wounds and 0.628-0.849 for chronic wounds. We also discuss factors affecting tracking performance and propose strategies to enhance implementation effectiveness.

Designing 3D-Printed Mesh-Covered Fluid Collecting Racks (MFCRs) to Prevent Moisture-Related COVID-19 Sampling Interruptions in Taiwan.

Background: A sampling platform (or table) set at the patient's side in a zero-exposure screening center (booth) might be used for specimen collection during public health crises such as the COVID-19 pandemic. However, repeated sanitization causes moisture problems. Such moisture problems would not only be noted by patients but also interrupt the sampling process. In this study, we aimed to develop 3D-printed mesh-covered fluid collecting racks (MFCRs) to address surface moisture problems to determine whether MFCRs can shorten the sampling time. Methods: This was an observational, descriptive, and cross-sectional study. We observed the reasons for sampling interruptions related to surface moisture problems among patients who used MFCRs or did not (April 28-30, 2022). We used a 3D printer to make an MFCR, which measured 14.5 cm in width and length and 1.0 cm in height. The MFCR allows the ethanol to drain through the mesh into the fluid collection rack below to leave a relatively dry surface on the mesh. Finally, we calculated the median time to finish sampling between MFCRs and non-MFCRs. Results: A total of 400 patients were randomly observed (using MFCRs, n = 200; non-MFCRs, n = 200). Patients in the non-MFCR group were more likely to interrupt the sampling process (n = 39, 19.5%) by noting surface moisture problems than those in the MFCR group (n = 3, 1.5%). Two of the major interruptions, "asking questions about the moist surface" (from 12% to 1%) and "slowing down their actions" (from 4.5% to 0.5%), were obviously improved by using MFCRs. Overall, the median sampling time was significantly shorter (p < 0.001) in the group using MFCRs (0.6 min) than in the group using non-MFCRs (1.5 min). The MFCRs shortened the sampling time by 60%, which might be associated with decreasing interruptions caused by surface moisture problems. Conclusions: The 3D printed MFCRs are suitable for handling surface moisture problems caused by repeated sanitizations. More importantly, the MFCRs might be associated with decreasing interruptions caused by moisture problems.

Loss of synaptopodin impairs mGluR5 and protein synthesis dependent mGluR-LTD at CA3-CA1 synapses.

Metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) is an important form of synaptic plasticity that occurs in many regions of the CNS and is the underlying mechanism for several learning paradigms. In the hippocampus, mGluR-LTD is manifested by the weakening of synaptic transmission and elimination of dendritic spines. Interestingly, not all spines respond or undergo plasticity equally in response to mGluR-LTD. A subset of dendritic spines containing synaptopodin (SP), an actin-associated protein, are critical for mGluR-LTD and protect spines from elimination through mGluR1 activity. The precise cellular function of SP is still enigmatic and it is still unclear how SP contributes to the functional aspect of mGluR-LTD despite of its modulation on the structural plasticity. In the present study, we show that the lack of SP impairs mGluR-LTD by negatively affecting the mGluR5-dependent activity. Such impairment of mGluR5 activity is accompanied by a significant decrease of surface mGluR5 level in SP knockout (SPKO) mice. Intriguingly, the remaining mGluR-LTD becomes a protein synthesis-independent process in the SPKO and is mediated instead by endocannabinoid signaling. These data show for the first time that the postsynaptic protein SP can regulate the locus of expression of mGluR-LTD and provide insight to our understanding of spine/synapse-specific plasticity. Significance statement: Hippocampal group I metabotropic glutamate receptor dependent long-term depression (mGluR-LTD), a form of learning and memory, is misregulated in many murine models of neurodevelopmental disorders. Despite extensive studies there is a paucity of information on the molecular mechanism underlying mGluR-LTD. Previously, we reported that loss of synaptopodin, an actin-associated protein found in a subset of mature dendritic spines, impairs mGluR-LTD. In the current study, we uncover the molecular and cellular deficits involved. We find that synaptopodin is required for the mGluR5-Homer interaction and uncover synaptopodin as a molecular switch for mGluR-LTD expression, as mGluR-LTD becomes protein synthesis-independent and relies on endocannabinoid signaling in synaptopodin knock-out. This work provides insight into synaptopodin as a gatekeeper to regulate mGluR-LTD at hippocampal synapses.

The adjusted impact of different severities of acute exacerbations and medications on the risk of developing dementia in COPD patients.

BACKGROUND: Although a relationship between chronic obstructive pulmonary disease (COPD) and dementia has been reported, the initial severity upon emergency department (ED) visits and the medications used have not been well evaluated as risk factors for increased dementia occurrence. We aimed to analyze the risks of dementia development over 5 years among patients with COPD compared to matched controls (primary) and the impact of different severities of acute exacerbations (AEs) of COPD and medications on the risk of dementia development among COPD patients (secondary). METHOD: This study used the Taiwanese government deidentified health care database. We enrolled patients during the 10-year study period (January 1, 2000, to December 31, 2010), and each patient was followed up for 5 years. Once these patients received a diagnosis of dementia or died, they were no longer followed up. The study group included 51,318 patients who were diagnosed with COPD and 51,318 matched (in terms of age, sex, and the number of hospital visits) non-COPD patients from the remaining patients as the control group. Each patient was followed up for 5 years to analyze the risk of dementia with Cox regression analysis. Data on medications (antibiotics, bronchodilators, corticosteroids) and severity at the initial ED visit (ED treatment only, hospital admission, or ICU admission) were collected for both groups, as well as demographics and baseline comorbidities, which were considered confounding factors. RESULTS: In the study and control groups, 1,025 (2.0%) and 423 (0.8%) patients suffered from dementia, respectively. The unadjusted HR for dementia was 2.51 (95% CI: 2.24-2.81) in the study group. Bronchodilator treatment was associated with the HRs, especially among those who received long-term (> 1 month) treatment (HR = 2.10, 95% CI: 1.91-2.45). Furthermore, among 3,451 AE of COPD patients who initially visited the ED, patients who required ICU admission (n = 164, 4.7%) had a higher risk of dementia occurrence (HR = 11.05, 95% CI: 7.77-15.71). CONCLUSION: Bronchodilator administration might be associated with a decreased risk of dementia development. More importantly, patients who suffered AEs of COPD and initially visited the ED and required ICU admission had a higher risk of developing dementia.

Sulfated Hyperbranched and Linear Polyglycerols Modulate HMGB1 and Morphological Plasticity in Neural Cells.

The objective of this study was to establish if polyglycerols with sulfate or sialic acid functional groups interact with high mobility group box 1 (HMGB1), and if so, which polyglycerol could prevent loss of morphological plasticity in excitatory neurons in the hippocampus. Considering that HMGB1 binds to heparan sulfate and that heparan sulfate has structural similarities with dendritic polyglycerol sulfates (dPGS), we performed the experiments to show if polyglycerols can mimic heparin functions by addressing the following questions: (1) do dendritic and linear polyglycerols interact with the alarmin molecule HMGB1? (2) Does dPGS interaction with HMGB1 influence the redox status of HMGB1? (3) Can dPGS prevent the loss of dendritic spines in organotypic cultures challenged with lipopolysaccharide (LPS)? LPS plays a critical role in infections with Gram-negative bacteria and is commonly used to test candidate therapeutic agents for inflammation and endotoxemia. Pathologically high LPS concentrations and other stressful stimuli cause HMGB1 release and post-translational modifications. We hypothesized that (i) electrostatic interactions of hyperbranched and linear polysulfated polyglycerols with HMGB1 will likely involve sites similar to those of heparan sulfate. (ii) dPGS can normalize HMGB1 compartmentalization in microglia exposed to LPS and prevent dendritic spine loss in the excitatory hippocampal neurons. We performed immunocytochemistry and biochemical analyses combined with confocal microscopy to determine cellular and extracellular locations of HMGB1 and morphological plasticity. Our results suggest that dPGS interacts with HMGB1 similarly to heparan sulfate. Hyperbranched dPGS and linear sulfated polymers prevent dendritic spine loss in hippocampal excitatory neurons. MS/MS analyses reveal that dPGS-HMGB1 interactions result in fully oxidized HMGB1 at critical cysteine residues (Cys23, Cys45, and Cys106). Triply oxidized HMGB1 leads to the loss of its pro-inflammatory action and could participate in dPGS-mediated spine loss prevention. LPG-Sia exposure to HMGB1 results in the oxidation of Cys23 and Cys106 but does not normalize spine density.

Development and Validation of a Prediction Model for Chronic Post-Surgical Pain After Thoracic Surgery in Elderly Patients: A Retrospective Cohort Study.

Purpose: Chronic post-surgical pain (CPSP) is one of the adverse outcomes after surgery, especially in thoracotomy. However, the prevalence of CPSP in elderly adults (≥65 years), is still limited. Therefore, the present study was undertaken to establish and validate the prediction model of CPSP in those patients after thoracic surgery, including thoracotomy and video-assisted thoracoscopic surgery. Patients and Methods: This retrospective, observational single-center cohort study was conducted in Nanfang Hospital, Southern Medical University, which randomly and consecutively collected 577 elderly patients who underwent thoracic surgery between January 1, 2017, and December 31, 2020. According to the Akaike information criterion, the prediction model was built based on all the data and was validated by calibration with 500 bootstrap samples. Results: The mean age of participants was 69.09±3.80 years old, and 63.1% were male. The prevalence of CPSP was 26.9%. Age more than 75 years, BMI, blood loss, longer length of hospital stays, and higher pre-operative neutrophil count were associated with CPSP. Except for these factors, we incorporated history of drinking to build up the prediction model. The areas under the curve (AUCs) of the prediction models were 0.66 (95% CI, 0.61-0.71) and 0.64 (95% CI, 0.59-0.69) in the observational and validation cohorts, respectively. And the calibration curve of the predictive model showed a good fit between the predicted risk of CPSP and observed outcomes in elderly patients. Conclusion: The present developed model may help clinicians to find high-risk elderly patients with CPSP after thoracic surgery and take corresponding measures in advance to reduce the incidence of CPSP and improve their life quality.

Cross-talk between GABAergic postsynapse and microglia regulate synapse loss after brain ischemia.

Microglia interact with neurons to facilitate synapse plasticity; however, signal(s) contributing to microglia activation for synapse elimination in pathology are not fully understood. Here, using in vitro organotypic hippocampal slice cultures and transient middle cerebral artery occlusion (MCAO) in genetically engineered mice in vivo, we report that at 24 hours after ischemia, microglia release brain-derived neurotrophic factor (BDNF) to downregulate glutamatergic and GABAergic synapses within the peri-infarct area. Analysis of the cornu ammonis 1 (CA1) in vitro shows that proBDNF and mBDNF downregulate glutamatergic dendritic spines and gephyrin scaffold stability through p75 neurotrophin receptor (p75NTR) and tropomyosin receptor kinase B (TrkB) receptors, respectively. After MCAO, we report that in the peri-infarct area and in the corresponding contralateral hemisphere, similar neuroplasticity occurs through microglia activation and gephyrin phosphorylation at serine-268 and serine-270 in vivo. Targeted deletion of the Bdnf gene in microglia or GphnS268A/S270A (phospho-null) point mutations protects against ischemic brain damage, neuroinflammation, and synapse downregulation after MCAO.

[Retracted] Silencing NOB1 enhances doxorubicin antitumor activity of the papillary thyroid carcinoma in vitro and in vivo.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting assay data shown in Figs. 2 and 5, and the tumour images shown in Fig. 6A, were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 33: 1551-1559, 2015; DOI: 10.3892/or.2015.3730].

Stabilization of Spine Synaptopodin by mGluR1 Is Required for mGluR-LTD.

Dendritic spines, actin-rich protrusions forming the postsynaptic sites of excitatory synapses, undergo activity-dependent molecular and structural remodeling. Activation of Group 1 metabotropic glutamate receptors (mGluR1 and mGluR5) by synaptic or pharmacological stimulation, induces LTD, but whether this is accompanied with spine elimination remains unresolved. A subset of telencephalic mushroom spines contains the spine apparatus (SA), an enigmatic organelle composed of stacks of smooth endoplasmic reticulum, whose formation depends on the expression of the actin-bundling protein Synaptopodin. Allocation of Synaptopodin to spines appears governed by cell-intrinsic mechanisms as the relative frequency of spines harboring Synaptopodin is conserved in vivo and in vitro Here we show that expression of Synaptopodin/SA in spines is required for induction of mGluR-LTD at Schaffer collateral-CA1 synapses of male mice. Post-mGluR-LTD, mushroom spines lacking Synaptopodin/SA are selectively lost, whereas spines harboring it are preserved. This process, dependent on activation of mGluR1 but not mGluR5, is conserved in mature mouse neurons and rat neurons of both sexes. Mechanistically, we find that mGluR1 supports physical retention of Synaptopodin within excitatory spine synapses during LTD while triggering lysosome-dependent degradation of the protein residing in dendritic shafts. Together, these results reveal a cellular mechanism, dependent on mGluR1, which enables selective preservation of stronger spines containing Synaptopodin/SA while eliminating weaker ones and potentially countering spurious strengthening by de novo recruitment of Synaptopodin. Overall, our results identify spines with Synaptopodin/SA as the locus of mGluR-LTD and underscore the importance of the molecular microanatomy of spines in synaptic plasticity.SIGNIFICANCE STATEMENT Long-term changes in functional synaptic strength are associated with modification of synaptic connectivity through stabilization or elimination of dendritic spines, the postsynaptic locus of excitatory synapses. How heterogeneous spine microanatomy instructs spine remodeling after long-term synaptic depression (LTD) remains unclear. Metabotropic glutamate receptors mGluR1 and mGluR5 induce a form of LTD critical to circuit function in physiological and disease conditions. Our results identify spines containing the protein Synaptopodin, which enables local assembly of a spine apparatus, as the locus of expression of mGluR-LTD and demonstrate a specific role of mGluR1 in promoting selective loss after mGluR-LTD of mature dendritic spines lacking Synaptopodin/spine apparatus. These findings highlight the fundamental contribution of spine microanatomy in selectively enabling functional and structural plasticity.

Novel ADNP Syndrome Mice Reveal Dramatic Sex-Specific Peripheral Gene Expression With Brain Synaptic and Tau Pathologies.

BACKGROUND: ADNP is essential for embryonic development. As such, de novo ADNP mutations lead to an intractable autism/intellectual disability syndrome requiring investigation. METHODS: Mimicking humans, CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 editing produced mice carrying heterozygous Adnp p.Tyr718∗ (Tyr), a paralog of the most common ADNP syndrome mutation. Phenotypic rescue was validated by treatment with the microtubule/autophagy-protective ADNP fragment NAPVSIPQ (NAP). RESULTS: RNA sequencing of spleens, representing a peripheral biomarker source, revealed Tyr-specific sex differences (e.g., cell cycle), accentuated in females (with significant effects on antigen processing and cellular senescence) and corrected by NAP. Differentially expressed, NAP-correctable transcripts, including the autophagy and microbiome resilience-linked FOXO3, were also deregulated in human patient-derived ADNP-mutated lymphoblastoid cells. There were also Tyr sex-specific microbiota signatures. Phenotypically, Tyr mice, similar to patients with ADNP syndrome, exhibited delayed development coupled with sex-dependent gait defects. Speech acquisition delays paralleled sex-specific mouse syntax abnormalities. Anatomically, dendritic spine densities/morphologies were decreased with NAP amelioration. These findings were replicated in the Adnp+/- mouse, including Foxo3 deregulation, required for dendritic spine formation. Grooming duration and nociception threshold (autistic traits) were significantly affected only in males. Early-onset tauopathy was accentuated in males (hippocampus and visual cortex), mimicking humans, and was paralleled by impaired visual evoked potentials and correction by acute NAP treatment. CONCLUSIONS: Tyr mice model ADNP syndrome pathology. The newly discovered ADNP/NAP target FOXO3 controls the autophagy initiator LC3 (microtubule-associated protein 1 light chain 3), with known ADNP binding to LC3 augmented by NAP, protecting against tauopathy. NAP amelioration attests to specificity, with potential for drug development targeting accessible biomarkers.

The effect of the head-up position on cardiopulmonary resuscitation: a systematic review and meta-analysis.

OBJECTIVE: Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. METHODS: Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). RESULTS: Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11-13.64; p < 0.01; I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84-13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD - 13.66; 95% CI - 18.6 to -8.71; p < 0.01; I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD - 1.63; 95% CI - 10.77-7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31-2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression-decompression (ACD) and impedance threshold (ITD) devices. CONCLUSION: In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Comparative effectiveness of ultrasound-guided and anatomic landmark percutaneous dilatational tracheostomy: A systematic review and meta-analysis.

INTRODUCTION: Ultrasound-guided tracheostomy (UGT) and bronchoscope-guided tracheostomy (BGT) have been well compared. However, the differences in benefits between UGT and landmark tracheostomy (LT) have not been addressed and, in particular, lack a detailed meta-analysis. We aimed to compare the first-pass success, complication rate, major bleeding rate, and tracheostomy procedure time between UGT and LT. METHODS: In a systematic review, relevant databases were searched for studies comparing UGT with LT in intubated patients. The primary outcome was the odds ratio (OR) of first-pass success. The secondary outcomes were the OR of complications, OR of major bleeding, and standardized mean difference (SMD) of the total tracheostomy procedure time. RESULTS: The meta-analysis included three randomized controlled studies (RCTs) and one nonrandomized controlled study (NRS), comprising 474 patients in total. Compared with LT, UGT increased first-pass success (OR: 4.287; 95% confidence interval [CI]: 2.308 to 7.964) and decreased complications (OR: 0.422; 95% CI: 0.249 to 0.718). However, compared with LT, UGT did not significantly reduce major bleeding (OR: 0.374; 95% CI: 0.112 to 1.251) or the total tracheostomy placement time (SMD: -0.335; 95% CI: -0.842 to 0.172). CONCLUSIONS: Compared with LT, real-time UGT increases first-pass success and decreases complications. However, UGT was not associated with a significant reduction in the major bleeding rate. The total tracheostomy placement time comparison between UGI and LT was inconclusive.

Clinical treatment and medication in decreasing the development of major depression caused by spinal fracture.

BACKGROUND: Chronic pain and limited activities of daily living after spinal fracture may induce the occurrence of major depression (MD); however, risk factors regarding medications, surgical intervention, and severity of fracture are unclear. We aimed to analyze risk factors of MD development after spinal fracture. METHODS: This was a retrospective database study, using the health care database of the Taiwan government. We included 11,225 patients with new spinal fracture (study group), and 33,675 matched patients without fracture (comparison group). We respectively reviewed data of each participant for 3 years to assess the development of MD. The Cox proportional hazards model was used to determine the prevalence of MD, after adjusting for patient demographics, medications, surgical interventions, spinal cord involvement, and postfracture comorbidities. RESULTS: In total, 187 fracture patients (1.7%) and 281 nonfracture patients (0.8%) developed new-onset MD (hazard ratio [HR]:1.96, (95% confidence interval [CI]: 1.63-2.36)). Spinal cord involvement (HR: 2.96, 95% CI: 2.54-3.42) and postfracture comorbidities (HR: 3.51, 95% CI: 2.86-3.97) obviously increased the risk of MD. CONCLUSIONS: Patients with spinal fracture (spinal cord involvement and postfracture comorbidities) were more likely to develop MD. Early surgical interventions (vertebroplasty) and medications (narcotics) may decrease the risk of MD.

Long-Term Adverse Effects of Oxidative Stress on Rat Epididymis and Spermatozoa.

Oxidative stress is a common culprit of several conditions associated with male fertility. High levels of reactive oxygen species (ROS) promote impairment of sperm quality mainly by decreasing motility and increasing the levels of DNA oxidation. Oxidative stress is a common feature of environmental pollutants, chemotherapy and other chemicals, smoke, toxins, radiation, and diseases that can have negative effects on fertility. Peroxiredoxins (PRDXs) are antioxidant enzymes associated with the protection of mammalian spermatozoa against oxidative stress and the regulation of sperm viability and capacitation. In the present study, we aimed to determine the long-term effects of oxidative stress in the testis, epididymis and spermatozoa using the rat model. Adult male rats were treated with tert-butyl hydroperoxide (t-BHP) or saline (control group), and reproductive organs and spermatozoa were collected at 3, 6, and 9 weeks after the end of treatment. We determined sperm DNA oxidation and motility, and levels of lipid peroxidation and protein expression of antioxidant enzymes in epididymis and testis. We observed that cauda epididymal spermatozoa displayed low motility and high DNA oxidation levels at all times. Lipid peroxidation was higher in caput and cauda epididymis of treated rats at 3 and 6 weeks but was similar to control levels at 9 weeks. PRDX6 was upregulated in the epididymis due to t-BHP; PRDX1 and catalase, although not significant, followed similar trend of increase. Testis of treated rats did not show signs of oxidative stress nor upregulation of antioxidant enzymes. We concluded that t-BHP-dependent oxidative stress promoted long-term changes in the epididymis and maturing spermatozoa that result in the impairment of sperm quality.

Multicenter analysis of long-term oncologic outcomes of hepatectomy for elderly patients with hepatocellular carcinoma.

BACKGROUND: Aging of the population and prolonged life expectancy have significantly increased the number of elderly patients undergoing hepatectomy for hepatocellular carcinoma (HCC). However, potential benefits, especially long-term oncologic outcomes of hepatectomy for elderly patients with HCC remain unclear. METHOD: Patients treated with curative-intent hepatectomy for HCC in 8 Chinese hospitals were enrolled. Patients were divided into the elderly (≥70 years old) and younger (<70 years old) groups. Overall survival (OS), cancer-specific survival (CSS), and time-to-recurrence (TTR) were compared. Risk factors of CSS and TTR were evaluated by univariable and multivariable competing-risk regression analyses. RESULTS: Of 2134 patients, 259 (12.1%) and 1875 (87.9%) were elderly and younger aged, respectively. Postoperative 30-day and 90-day mortality was comparable among elderly and younger patients. Compared with younger patients, the elderly had a worse 5-year OS (49.4% vs. 55.3%, P = 0.032), yet a better 5-year CCS (74.5% vs. 61.0%, P = 0.005) and a lower 5-year TTR (33.7% vs. 44.9%, P < 0.001), respectively. Multivariable analyses identified that elder age was independently associated with more favorable CSS (HR 0.74, 95%CI 0.58-0.90, P = 0.011) and TTR (0.69, 0.53-0.88, P < 0.001) but was not associated with OS (P = 0.136). CONCLUSIONS: Age by itself is not a contraindication to surgery, and selected elderly patients with HCC can benefit from hepatectomy. Compared with younger patients, elderly patients have noninferior oncologic outcomes following hepatectomy for HCC.