Boosting with variant-matched adenovirus-based vaccines promotes neutralizing antibody responses against SARS-CoV-2 Omicron sublineages in mice.

Global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron subvariants, such as BA.4, BA.5 and XBB.1.5, has been leading the recent wave of coronavirus disease 2019 (COVID-19). Unique mutations in the spike proteins of these emerging Omicron subvariants caused immune evasion from the pre-existing protective immunity induced by vaccination or natural infection. Previously, we developed AdCLD-CoV19-1, a non-replicating recombinant adenoviral vector that encodes the receptor binding domain of the spike protein of the ancestral SARS-CoV-2 strain. Based on the same recombinant adenoviral vector platform, updated vaccines that cover unique mutations found in each Omicron subvariant, including BA.1, BA.2, BA.4.1 and BA.5, were constructed. Preclinical studies revealed that each updated vaccine as a booster shot following primary vaccination targeting the ancestral strain improved neutralizing antibody responses against the pseudovirus of its respective strain most effectively. Of note, boosting with a vaccine targeting the BA.1 or BA.2 Omicron subvariant was most effective in neutralization against the pseudovirus of the BA.2.75 strain, whereas BA.4.1/5-adapted booster shots were most effective in neutralization against the BQ.1, BQ1.1 and BF.7 strains. Therefore, it is imperative to develop a vaccination strategy that can cover the unique spike mutations of currently circulating Omicron subvariants in order to prevent the next wave of COVID-19.

Impact of long-acting injectable aripiprazole on the concomitant medication and antipsychotic polypharmacy: a retrospective, observational study of 127 patients with psychosis.

Antipsychotic polypharmacy (APP) has become prevalent over the years, but several concerns have been raised over APP. Accumulating evidence suggests that aripiprazole long-acting injectable (LAI) may reduce the rate of APP, but the association remains speculative. This retrospective observational study included 127 patients with psychosis and observed them for 1.8 ±â€…1.3 years, up to 4 years. Prescription data of antipsychotics (APs), mood stabilisers, benzodiazepines, and anti-extrapyramidal side effect medications were obtained at baseline and the last observation. Daily chlorpromazine equivalent (CPZ) dose of APs decreased from 124.40 ±â€…235.35 mg to 77.95 ±â€…210.36 mg (P = 0.027). The daily dose of anticholinergics and beta-blockers also significantly decreased after introducing aripiprazole LAI. Among the patients having APP, the number of concurrent APs along with daily CPZ dose of APs decreased after initiation of aripiprazole LAI from 1.28 ±â€…0.62 to 0.85 ±â€…0.73 (P < 0.001) and 298.33 ±â€…308.70 mg to 155.43 ±â€…280.53 mg (P = 0.004), respectively. Treatment with aripiprazole LAI for up to 4 years in patients with psychosis was associated with a reduced number of prescribed APs in patients having an APP and a reduced dose of APs and concurrent psychotropic medications.

Comparison of Postoperative Nausea and Vomiting Incidence between Remimazolam and Sevoflurane in Tympanoplasty with Mastoidectomy: A Single-Center, Double-Blind, Randomized Controlled Trial.

Background and Objectives: Postoperative nausea and vomiting (PONV) is a common adverse effect of general anesthesia, especially in middle ear surgery. Remimazolam is a newer benzodiazepine recently approved for use in general anesthesia. This study aimed to compare the incidence rate of PONV after tympanoplasty with mastoidectomy between using remimazolam and sevoflurane. Materials and Methods: This study included 80 patients undergoing elective tympanoplasty with mastoidectomy. The patients were randomly assigned to either the remimazolam or sevoflurane group. The primary outcome was the incidence rate of PONV 12 h after surgery. The secondary outcomes were the incidence rate of PONV 12-24 and 24-48 h after surgery, severity of PONV, incidence rate of vomiting, administration of rescue antiemetics, hemodynamic stability, and recovery profiles. Results: The incidence rate of PONV 0-12 h after tympanoplasty with mastoidectomy was significantly lower in the remimazolam group compared with that in the sevoflurane group (28.9 vs. 57.9%; p = 0.011). However, the incidence rate of delayed PONV did not differ between the two groups. PONV severity in the early periods after the surgery was significantly lower in the remimazolam group than in the sevoflurane group. The incidence rate of adverse hemodynamic events was lower in the remimazolam group than in the sevoflurane group, but there was no difference in the overall trends of hemodynamic data between the two groups. There was no difference in recovery profiles between the two groups. Conclusions: Remimazolam can significantly reduce the incidence rate of early PONV after tympanoplasty with mastoidectomy under general anesthesia.

Evaluating Biliary Malignancy with Measured and Calculated Ultra-high b-value Diffusion-weighted MR Imaging at 3T.

PURPOSE: Although diffusion-weighted imaging (DWI) with ultra-high b-values is reported to be advantageous in the detection of some tumors, its applicability is not yet known in biliary malignancy. Therefore, this study aimed to evaluate the impact of measured b = 1400 s/mm2 (M1400) and calculated b = 1400 s/mm2 (C1400) DWI on image quality and quality of lesion discernibility using a modern 3T MR system compared to conventional b = 800 s/mm2 DWI (M800). METHODS: We evaluated 56 patients who had pathologically proven biliary malignancy. All the patients underwent preoperative or baseline 3T MRI using DWI (b = 50, 400, 800, and 1400 s/mm2). The calculated DWI was obtained using a conventional DWI set (b = 50, 400, and 800). The tumor-to-bile contrast ratio (CR) and tumor SNR were compared between the different DWI images. Likert scores were given on a 5-point scale to assess the overall image quality, overall artifacts, ghost artifacts, misregistration artifacts, margin sharpness, and lesion discernibility. Repeated-measures analysis of variance with post hoc analyses was used for statistical evaluations. RESULTS: The CR of the tumor-to-bile was significantly higher in both M1400 and C1400 than in M800 (Pa < 0.01). SNRs were significantly higher in M800, followed by C1400 and M1400 (Pa < 0.01). Lesion discernibility was significantly improved for M1400, followed by C1400 and M800 for both readers (Pa < 0.01). CONCLUSION: Using a 3T MRI, both measured and calculated DWI with an ultra-high b-value offer superior lesion discernibility for biliary malignancy compared to the conventional DWI.

Comparison of parameter types for the calibration of noninvasive continuous cardiac output monitoring of patients undergoing lumbar spinal surgery in the prone position.

BACKGROUND: Cardiac output (CO) decreases on reversing the patient's position to the prone position. Estimated continuous cardiac output (esCCO) systems can noninvasively and continuously monitor CO calibrated by patient information or transesophageal echocardiogram (TEE). OBJECTIVE: To compare the accuracy, precision, and trending ability of two calibration methods of CO estimation in patients in prone position. METHODS: The CO estimates calibrated by TEE (esT) and patient information (esP) of 26 participants were included. CO was collected at four time points. The accuracy and precision of agreement were evaluated using the Bland-Altman method. A four-quadrant plot was used for trending ability analysis. RESULTS: The bias between esP and TEE and between esT and TEE was 0.2594 L/min (95% limits of agreement (LoA): -1.8374 L/min to 2.3562 L/min) and 0.0337 L/min (95% LoA: -0.7381 L/min to 0.8055 L/min), respectively. A strong correlation was found between ΔesP and ΔTEE (p< 0.001, CCC = 0.700) and between ΔesT and ΔTEE (p< 0.001, CCC = 0.794). The concordance rates between ΔesP and ΔTEE and between ΔesT and ΔTEE were 91.9% and 97.1%, respectively. CONCLUSION: Despite limited accuracy and precision, esP showed acceptable trending ability. The trending ability of esCCO calibrated by the reference TEE value was comparable with that of TEE.

Comparing the Pericapsular Nerve Group Block and the Lumbar Plexus Block for Hip Fracture Surgery: A Single-Center Randomized Double-Blinded Study.

Lumbar plexus blocks (LPBs) are routinely employed for analgesia in hip fracture surgery; however, a novel regional technique, the pericapsular nerve group (PENG) block, potentially offers comparable pain reduction while preserving motor function. Patients aged 45-90 years who underwent hip fracture surgery were allocated to receive either a PENG block or an LPB for analgesia. The primary outcome was the incidence of quadriceps motor block (defined as the paresis or paralysis of the knee extension) at 12 h postoperatively. The secondary outcomes included the performance time, the time to first analgesic requirement, postoperative intravenous (IV) fentanyl consumption, the ability to undergo physiotherapy at 24 and 48 h, complications, sensory and motor block assessments, postoperative numeric rating scale (NRS) pain scores, and patient outcome questionnaires. There was a significantly lower incidence of quadriceps motor block at 6 h (26.7% vs. 80.0%; p < 0.001) and at 12 h (20.0% vs. 56.7%; p = 0.010). The PENG block provided better preservation of the sensory block as well as better performance time (p < 0.001) and time to first analgesia requirement (p = 0.034), whereas the LPB resulted in lower postoperative IV fentanyl consumption at 24 h (p = 0.013). The PENG block demonstrated superiority over the LPB in preserving quadriceps strength and patient satisfaction without any substantial complications, despite higher opioid consumption within the first 24 h post-surgery.

Reduced Opioid Consumption with Pericapsular Nerve Group Block for Hip Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

The pericapsular nerve group (PENG) block targets the nerves innervating the anterior hip surface; however, few studies on this technique are currently available. We investigated the effects of the PENG block on postoperative opioid consumption after a hip surgery. This was a randomized, double-blind, placebo-controlled study conducted at a single institution. Fifty patients undergoing hip surgery were randomly allocated, 25 in each group, to receive a PENG block either using 25 mL of 0.5% ropivacaine (PENG group) or 25 mL of saline (control group). The primary outcome was the total opioid consumption 24 h postoperatively. The secondary outcomes were postoperative pain scores, time to first opioid demand, sensory block efficiency, quadriceps muscle strength, complications, and patient satisfaction. Compared with those in the control group, patients in the PENG group had a significantly lower total opioid consumption 24 h postoperatively (440.72 ± 242.20 µg vs. 611.07 ± 313.89 µg, P = 0.037) and significantly lower pain scores at 30 min postblock and 6 postoperatively (P < 0.001 and P < 0.001, respectively). The time to first opioid demand was significantly shorter in the control group than in the PENG group (P < 0.001). Sensory block effectiveness was better in the PENG group 30 min postblock and 6 and 12 h postoperatively than in the control group. Patient satisfaction was also better in the PENG group than in the control group. There were no differences in the other outcomes. The PENG block reduced the total opioid consumption in the first 24 h after hip surgery with no significant effects on quadriceps muscle strength and complication rate. This study was registered at the Korea Clinical Research Information Service (cris.nih.go.kr; Reg. No. KCT0006348) on July 16, 2021.

Anesthetic Management of Upper Tracheal Cancer Resection and Reconstruction: A Case Report.

Tracheal tumor resection and reconstruction is the primary treatment for tracheal tumors. The trachea is the surgical site as well as an important channel to ensure ventilation and maintain oxygenation during surgery. In this report, we describe the successful management of an upper tracheal tumor in a 50-year-old patient. The tumor was situated approximately 2-3 cm below the vocal cords, occluding the tracheal lumen by 80%. Conventional orotracheal intubation was expected to be impossible, and the patient was managed with an I-Gel supraglottic airway for mechanical ventilation with the assistance of venovenous extracorporeal membrane oxygenation (VV ECMO). After securing tracheal intubation via the tracheostomy site, VV ECMO was weaned off, and mechanical ventilation was changed to tracheal intubation. Eventually, tracheal tumor resection and reconstruction were successfully performed under general anesthesia. No specific events occurred during anesthetic management. Careful preoperative planning and good teamwork made the procedure possible without complications.

Hypervascular transformation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid-enhanced MRI: long-term follow-up in a surveillance cohort.

OBJECTIVES: With the increasing use of gadoxetic acid-enhanced MRI for HCC surveillance, hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) are frequently encountered. We investigated the rate of these nodules with hypervascular transformation, which suggests hepatocarcinogenesis, by using a prospectively collected longitudinal surveillance cohort data. METHODS: This study included 382 prospectively enrolled patients at high risk for developing HCC who underwent 1-3 rounds of bi-annual surveillance gadoxetic acid-enhanced MRI. MRI was analyzed to detect HBP hypointense nodules without APHE. Follow-up dynamic CTs and MRIs were evaluated to detect hypervascular transformation of the nodules. Cox proportional hazards regression analyses were used to find predictors for hypervascular transformation. RESULTS: A total of 76 HBP hypointense nodules without APHE were found in 48 patients, giving a prevalence of 12.6% (48/382). The mean nodule size was 10.8 mm, with 43.4% (33/76) being ≥ 10 mm. Over a median follow-up of 78.6 months, 19 nodules (25.0%) showed hypervascular transformation, all of which demonstrated typical imaging features of HCC. On multivariable Cox-regression analysis, size (≥ 10 mm) was the only independent predictor of hypervascular transformation (hazard ratio, 3.31; 95% confidence interval, 1.21-9.05). The cumulative incidence of hypervascular transformation at 12 and 60 months of nodules ≥ 10 mm was 12.3% and 50.4%, respectively, while that of nodules < 10 mm was 2.5% and 13.9%, respectively. CONCLUSIONS: About half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC at 5 years of follow-up, indicating the necessity for cautious monitoring with an augmented and extended follow-up schedule for these nodules. KEY POINTS: • The prevalence of HBP hypointense nodules without APHE was 12.6% in a prospectively recruited population at high risk of developing HCC. • Nodule size ≥ 10 mm was significantly associated with hypervascular transformation, and approximately half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC during 5 years of follow-up. • Given the risk of malignant transformation, HBP hypointense nodules ≥ 10 mm without APHE should be closely monitored.

Improving the Safety of Mesenchymal Stem Cell-Based Ex Vivo Therapy Using Herpes Simplex Virus Thymidine Kinase.

Human mesenchymal stem cells (MSCs) are multipotent stem cells that have been intensively studied as therapeutic tools for a variety of disorders. To enhance the efficacy of MSCs, therapeutic genes are introduced using retroviral and lentiviral vectors. However, serious adverse events (SAEs) such as tumorigenesis can be induced by insertional mutagenesis. We generated lentiviral vectors encoding the wild-type herpes simplex virus thymidine kinase (HSV-TK) gene and a gene containing a point mutation that results in an alanine to histidine substitution at residue 168 (TK(A168H)) and transduced expression in MSCs (MSC-TK and MSC-TK(A168H)). Transduction of lentiviral vectors encoding the TK(A168H) mutant did not alter the proliferation capacity, mesodermal differentiation potential, or surface antigenicity of MSCs. The MSC-TK(A168H) cells were genetically stable, as shown by karyotyping. MSC-TK(A168H) responded to ganciclovir (GCV) with an half maximal inhibitory concentration (IC50) value 10-fold less than that of MSC-TK. Because MSC-TK(A168H) cells were found to be non-tumorigenic, a U87-TK(A168H) subcutaneous tumor was used as a SAE-like condition and we evaluated the effect of valganciclovir (vGCV), an oral prodrug for GCV. U87-TK(A168H) tumors were more efficiently ablated by 200 mg/kg vGCV than U87-TK tumors. These results indicate that MSC-TK(A168H) cells appear to be pre-clinically safe for therapeutic use. We propose that genetic modification with HSV-TK(A168H) makes allogeneic MSC-based ex vivo therapy safer by eliminating transplanted cells during SAEs such as uncontrolled cell proliferation.

Alterations in blood proteins in the prodromal stage of bipolar II disorders.

Although early intervention may help prevent the progression of bipolar disorder, there are some controversies over early pharmacological intervention. In this study, we recruited 40 subjects in the prodromal stage of BD-II (BP), according to bipolar at-risk state criteria. We compared the expression of their plasma proteins with that of 48 BD-II and 75 healthy control (HC) to identify markers that could be detected in a high-risk state. The multiple reaction monitoring method was used to measure target peptide levels with high accuracy. A total of 26 significant peptides were identified through analysis of variance with multiple comparisons, of which 19 were differentially expressed in the BP group when compared to the BD-II and HC groups. Two proteins were overexpressed in the BP group; and were related to pro-inflammation and impaired neurotransmission. The other under-expressed peptides in the BP group were related to blood coagulation, immune reactions, lipid metabolism, and the synaptic plasticity. In this study, significant markers observed in the BP group have been reported in patients with psychiatric disorders. Overall, the results suggest that the pathophysiological changes included in BD-II had already occurred with BP, thus justifying early pharmacological treatment to prevent disease progression.

Acute Abdominal Pain due to Accessory Splenic Infarction in an Adult: A Case Report.

Accessory spleens are common congenital anatomic variations that are usually asymptomatic. On the other hand, they can be clinically significant if complicated by hemorrhage, torsion, or infarction. This paper describes a case of an infarcted accessory spleen in a 30-year-old male who presented with abdominal pain. Abdominal CT and MRI revealed an isolated mass, 4.5 cm in size, in the perisplenic area. An infarcted accessory spleen was suspected. The patient underwent laparoscopic accessory splenectomy. Histopathology identified the mass as splenic tissue that had undergone ischemic necrosis. A definitive diagnosis of an infarcted accessory spleen was made, and the patient was discharged on day 5 after surgery symptom-free.

Intramuscular and Intermuscular Abdominal Fat Infiltration in COPD: A Propensity Score Matched Study.

Purpose: Low-attenuation muscle area (LAMA) and normal-attenuation muscle area (NAMA) indicate lipid-rich and lipid-poor skeletal muscle areas, respectively. Additionally, intermuscular adipose tissue (IMAT) indicates localized fat between muscle groups. In this study, we aimed to evaluate the intramuscular and intermuscular fat infiltration in individuals with chronic obstructive pulmonary disease (COPD) by performing quantitative assessment of the LAMA, NAMA, and IMAT observed on abdominopelvic computed tomography (APCT) images. Patients and Methods: We performed a cross-sectional study using data of subjects who underwent a general health examination with APCT at Ulsan University Hospital between March 2014 and June 2019. We classified the subjects into control and COPD groups based on age, smoking history, and pulmonary function results. We compared the attenuation and body mass index adjusted area of intra-abdominal components between the two groups using propensity score matching. We also evaluated these outcomes in COPD subgroups (mild and moderate stage subjects). Results: Overall, 6,965 subjects were initially enrolled, and 250 pairs of control and COPD subjects were selected after propensity score matching. The NAMA attenuation (unstandardized ß=-1.168, P<0.001) was lower, and the IMAT (unstandardized ß=0.042, P=0.006) and LAMA (unstandardized ß=0.120, P<0.001) indexes were greater in the COPD group than in the control group. In subgroup analysis, those with mild and moderate COPD also had high IMAT (unstandardized ß=0.037, P=0.009 and unstandardized ß=0.045, P<0.001) and LAMA (unstandardized ß=0.089, P=0.002 and unstandardized ß=0.147, P<0.001) indexes compared to the control subjects. However, the NAMA attenuation (unstandardized ß=-1.075, P<0.001) and NAMA index (unstandardized ß=-0.133, P=0.015) were significantly lower in moderate COPD subjects only. Conclusion: Our study showed that intramuscular and intermuscular abdominal fat infiltration could be present in subjects with mild COPD, and it might be exacerbated in those with moderate COPD.

Comparison of postoperative pulmonary complications between sugammadex and neostigmine in lung cancer patients undergoing video-assisted thoracoscopic lobectomy: a prospective double-blinded randomized trial.

BACKGROUND: Reversal of neuromuscular blockade (NMB) at the end of surgery is important for reducing postoperative residual NMB; this is associated with an increased risk of postoperative pulmonary complications (PPCs). Moreover, PPCs are associated with poor prognosis after video-assisted thoracoscopic surgery (VATS) for lobectomy. We compared the effects of two reversal agents, sugammadex and neostigmine, on the incidence of PPCs and duration of hospital stay in patients undergoing VATS lobectomy. METHODS: After VATS lobectomy was completed under neuromuscular monitoring, the sugammadex group (n = 46) received sugammadex 2 mg/kg, while the neostigmine group (n = 47) received neostigmine 0.05 mg/kg with atropine 0.02 mg/kg after at least the third twitch in response to the train of four stimulation. The primary outcome was incidence of PPCs. The secondary outcomes were duration of hospital stay and intensive care unit (ICU) admission. RESULTS: There was no significant difference in the incidence of PPCs for both the sugammadex and neostigmine groups (32.6% and 40.4%, respectively; risk difference = 0.08; 95% confidence interval = [-0.12, 0.27]; P = 0.434). The lengths of hospital (P = 0.431) and ICU (P = 0.964) stays were not significantly different between the two groups. CONCLUSIONS: The clinical use of sugammadex and neostigmine in NMB reversal for patients undergoing VATS lobectomy was not significantly different in the incidence of PPCs and duration of hospital and ICU stay.

ERK Regulates NeuroD1-mediated Neurite Outgrowth via Proteasomal Degradation.

Neurogenic differentiation 1 (NeuroD1) is a class B basic helix-loop-helix (bHLH) transcription factor and regulates differentiation and survival of neuronal and endocrine cells by means of several protein kinases, including extracellular signal-regulated kinase (ERK). However, the effect of phosphorylation on the functions of NeuroD1 by ERK has sparked controversy based on context-dependent differences across diverse species and cell types. Here, we evidenced that ERK-dependent phosphorylation controlled the stability of NeuroD1 and consequently, regulated proneural activity in neuronal cells. A null mutation at the ERK-dependent phosphorylation site, S274A, increased the half-life of NeuroD1 by blocking its ubiquitin-dependent proteasomal degradation. The S274A mutation did not interfere with either the nuclear translocation of NeuroD1 or its heterodimerization with E47, its ubiquitous partner and class A bHLH transcription factor. However, the S274A mutant increased transactivation of the E-box-mediated gene and neurite outgrowth in F11 neuroblastoma cells, compared to the wild-type NeuroD1. Transcriptome and Gene Ontology enrichment analyses indicated that genes involved in axonogenesis and dendrite development were downregulated in NeuroD1 knockout (KO) mice. Overexpression of the S274A mutant salvaged neurite outgrowth in NeuroD1-deficient mice, whereas neurite outgrowth was minimal with S274D, a phosphomimicking mutant. Our data indicated that a longer protein half-life enhanced the overall activity of NeuroD1 in stimulating downstream genes and neuronal differentiation. We propose that blocking ubiquitin-dependent proteasomal degradation may serve as a strategy to promote neuronal activity by stimulating the expression of neuron-specific genes in differentiating neurons.

Characterization of a human monoclonal antibody generated from a B-cell specific for a prefusion-stabilized spike protein of Middle East respiratory syndrome coronavirus.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection and continues to infect humans, thereby contributing to a high mortality rate (34.3% in 2019). In the absence of an available licensed vaccine and antiviral agent, therapeutic human antibodies have been suggested as candidates for treatment. In this study, human monoclonal antibodies were isolated by sorting B cells from patient's PBMC cells with prefusion stabilized spike (S) probes and a direct immunoglobulin cloning strategy. We identified six receptor-binding domain (RBD)-specific and five S1 (non-RBD)-specific antibodies, among which, only the RBD-specific antibodies showed high neutralizing potency (IC50 0.006-1.787 µg/ml) as well as high affinity to RBD. Notably, passive immunization using a highly potent antibody (KNIH90-F1) at a relatively low dose (2 mg/kg) completely protected transgenic mice expressing human DPP4 against MERS-CoV lethal challenge. These results suggested that human monoclonal antibodies isolated by using the rationally designed prefusion MERS-CoV S probe could be considered potential candidates for the development of therapeutic and/or prophylactic antiviral agents for MERS-CoV human infection.

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders.

Increasing evidence suggests estrogen and estrogen signaling pathway disturbances across psychiatric disorders. Estrogens are not only crucial in sexual maturation and reproduction but are also highly involved in a wide range of brain functions, such as cognition, memory, neurodevelopment, and neuroplasticity. To add more, the recent findings of its neuroprotective and anti-inflammatory effects have grown interested in investigating its potential therapeutic use to psychiatric disorders. In this review, we analyze the emerging literature on estrogen receptors and psychiatric disorders in cellular, preclinical, and clinical studies. Specifically, we discuss the contribution of estrogen receptor and estrogen signaling to cognition and neuroprotection via mediating multiple neural systems, such as dopaminergic, serotonergic, and glutamatergic systems. Then, we assess their disruptions and their potential implications for pathophysiologies in psychiatric disorders. Further, in this review, current treatment strategies involving estrogen and estrogen signaling are evaluated to suggest a future direction in identifying novel treatment strategies in psychiatric disorders.

Comparison of clinical performance of i-gelⓇ and Baska MaskⓇ during laparoscopic cholecystectomy.

BACKGROUND: The supraglottic airway device is an appropriate alternative to tracheal intubation in laparoscopic surgery. We compared the Baska MaskⓇ with i-gelⓇ by measuring the oropharyngeal leak pressure (OLP) and hemodynamic and respiratory parameters during laparoscopic cholecystectomy. METHODS: A total of 97 patients were randomly allocated to either i-gel group (n = 49) or Baska Mask group (n = 48). Insertion time, number of insertion attempts, fiber-optic view of the glottis, and OLP were recorded. Heart rate, mean arterial pressure, peak airway pressure (PAP), lung compliance, and perioperative complications were assessed before, during, and after pneumoperitoneum. RESULTS: There were no significant differences between the two groups regarding demographic data, insertion time, fiber-optic view of the glottis, and the use of airway manipulation. The OLP was higher in the Baska Mask group than in the i-gel group (29.6 ± 6.8 cmH2O and 26.7 ± 4.5 cmH2O, respectively; P = 0.014). Heart rate, mean arterial pressure, PAP, and lung compliance were not significantly different between the groups. The incidence of perioperative complications was small and not statistically significant. CONCLUSIONS: Both the i-gel and Baska Mask provided a satisfactory airway during laparoscopic cholecystectomy. Compared with the i-gel, the Baska Mask demonstrated a higher OLP.

Adjunctive use of anti-inflammatory drugs for schizophrenia: A meta-analytic investigation of randomized controlled trials.

OBJECTIVE: Recent evidence suggests that adjuvant anti-inflammatory agents could improve the symptoms of patients with schizophrenia. However, the effects of the adjuvant anti-inflammatory agents on cognitive function, general functioning and side effects have not yet been systematically investigated. The present meta-analysis aimed to explore the effects of anti-inflammatory agents in patients with schizophrenia comprehensively. METHOD: We performed a literature search in online databases, including PubMed, EMBASE and the Cochrane Database of Systematic Reviews. Randomized, placebo-controlled double-blind studies that investigated clinical outcomes including psychopathology, neurocognition, general functioning and extrapyramidal side effects were included. The examined anti-inflammatory agents included aspirin, celecoxib, omega-3 fatty acids, estrogen, selective estrogen receptor modulator, pregnenolone, N-acetylcysteine, minocycline, davunetide and erythropoietin. RESULTS: Sixty-two double-blind randomized clinical trials studying 2914 patients with schizophrenia met the inclusion criteria for quantitative analysis. Significant overall effects were found for anti-inflammatory agents for reducing total, positive and negative symptom scores in the Positive and Negative Syndrome Scale. Cognitive improvements were significant with minocycline and pregnenolone augmentation therapy. General functioning was significantly enhanced by overall anti-inflammatory agents. There were no significant differences in side effects compared with placebo. Baseline total Positive and Negative Syndrome Scale score and illness duration were identified as moderating factors in the effects of anti-inflammatory augmentation on psychiatric symptom improvements. CONCLUSION: The comparative evaluation of efficacy and safety supported the use of anti-inflammatory adjuvant therapy over the use of antipsychotics alone. However, future studies could focus on patients with homogeneous clinical profile to figure out more detailed effects of anti-inflammatory therapy.

Bacterial Outer Membrane Vesicles Provide Broad-Spectrum Protection against Influenza Virus Infection via Recruitment and Activation of Macrophages.

Influenza A virus (IAV) poses a constant worldwide threat to human health. Although conventional vaccines are available, their protective efficacy is type or strain specific, and their production is time-consuming. For the control of an influenza pandemic in particular, agents that are immediately effective against a wide range of virus variants should be developed. Although pretreatment of various Toll-like receptor (TLR) ligands have already been reported to be effective in the defense against subsequent IAV infection, the efficacy was limited to specific subtypes, and safety concerns were also raised. In this study, we investigated the protective effect of an attenuated bacterial outer membrane vesicle -harboring modified lipid A moiety of lipopolysaccharide (fmOMV) against IAV infection and the underlying mechanisms. Administration of fmOMV conferred significant protection against a lethal dose of pandemic H1N1, PR8, H5N2, and highly pathogenic H5N1 viruses; this broad antiviral activity was dependent on macrophages but independent of neutrophils. fmOMV induced recruitment and activation of macrophages and elicited type I IFNs. Intriguingly, fmOMV showed a more significant protective effect than other TLR ligands tested in previous reports, without exhibiting any adverse effect. These results show the potential of fmOMV as a prophylactic agent for the defense against influenza virus infection.