A transcriptional regulatory mechanism of genes in the tricarboxylic acid cycle in the heart.

The tricarboxylic acid (TCA) cycle plays a crucial role in mitochondrial ATP production in the healthy heart. However, in heart failure, the TCA cycle becomes dysregulated. Understanding the mechanism by which TCA cycle genes are transcribed in the healthy heart is an important prerequisite to understanding how these genes become dysregulated in the failing heart. PPARγ coactivator 1α (PGC-1α) is a transcriptional coactivator that broadly induces genes involved in mitochondrial ATP production. PGC-1α potentiates its effects through the coactivation of coupled transcription factors, such as estrogen-related receptor (ERR), nuclear respiratory factor 1 (Nrf1), GA-binding protein-a (Gabpa), and Yin Yang 1 (YY1). We hypothesized that PGC-1α plays an essential role in the transcription of TCA cycle genes. Thus, utilizing localization peaks of PGC-1α to TCA cycle gene promoters would allow the identification of coupled transcription factors. PGC-1α potentiated the transcription of 13 out of 14 TCA cycle genes, partly through ERR, Nrf1, Gabpa, and YY1. ChIP-sequencing showed PGC-1α localization peaks in TCA cycle gene promoters. Transcription factors with binding elements that were found proximal to PGC-1α peak localization were generally essential for the transcription of the gene. These transcription factor binding elements were well conserved between mice and humans. Among the four transcription factors, ERR and Gabpa played a major role in potentiating transcription when compared to Nrf1 and YY1. These transcription factor-dependent PGC-1α recruitment was verified with Idh3a, Idh3g, and Sdha promoters with DNA binding assay. Taken together, this study clarifies the mechanism by which TCA cycle genes are transcribed, which could be useful in understanding how those genes are dysregulated in pathological conditions.

The transcription factor NFIL3/E4BP4 regulates the developmental stage-specific acquisition of basophil function.

BACKGROUND: Basophils are rare but important effector cells in many allergic disorders. Contrary to their early progenitors, the terminal developmental processes of basophils in which they gain their unique functional properties are unknown. OBJECTIVE: We sought to identify a novel late-stage basophil precursor and a transcription factor regulating the terminal maturation of basophils. METHODS: Using flow cytometry, transcriptome analysis, and functional assays, we investigated the identification and functionality of the basophil precursors as well as basophil development. We generated mice with basophil-specific deletion of nuclear factor IL-3 (NFIL3)/E4BP4 and analyzed the functional impairment of NFIL3/E4BP4-deficient basophils in vitro and in vivo using an oxazolone-induced murine model of allergic dermatitis. RESULTS: We report a new mitotic transitional basophil precursor population (referred to as transitional basophils) that expresses the FcεRIα chain at higher levels than mature basophils. Transitional basophils are less responsive to IgE-linked degranulation but produce more cytokines in response to IL-3, IL-33, or IgE cross-linking than mature basophils. In particular, we found that the expression of NFIL3/E4BP4 gradually rises as cells mature from the basophil progenitor stage. Basophil-specific deletion of NFIL3/E4BP4 reduces the expression of genes necessary for basophil function and impairs IgE receptor signaling, cytokine secretion, and degranulation in the context of murine atopic dermatitis. CONCLUSIONS: We discovered transitional basophils, a novel late-stage mitotic basophil precursor cell population that exists between basophil progenitors and postmitotic mature basophils. We demonstrated that NFIL3/E4BP4 augments the IgE-mediated functions of basophils, pointing to a potential therapeutic regulator for allergic diseases.

Dynamic bidirectional regulation of NLRC3 and gammaherpesviruses during viral latency in B lymphocytes.

While most NOD-like receptors (NLRs) are predominately expressed by innate immune cells, NLRC3, an inhibitory NLR of immune signaling, exhibits the highest expression in lymphocytes. The role of NLRC3 or any NLRs in B lymphocytes is completely unknown. Gammaherpesviruses, including human Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV-68), establish latent infection in B lymphocytes, which requires elevated NF-κB. This study shows that during latent EBV infection of human B cells, viral-encoded latent membrane protein 1 (LMP1) decreases NLRC3 transcript. LMP1-induced-NF-κB activation suppresses the promoter activity of NLRC3 via p65 binding to the promoter. Conversely, NLRC3 inhibits NF-κB activation by promoting the degradation of LMP1 in a proteasome-dependent manner. In vivo, MHV-68 infection reduces Nlrc3 transcripts in splenocytes, and Nlrc3-deficient mice show greater viral latency than controls. These results reveal a bidirectional regulatory circuit in B lymphocytes, where viral latent protein LMP1 reduces NLRC3 expression, while NLRC3 disrupts gammaherpesvirus latency, which is an important step for tumorigenesis.

Assessment of Adaptive Functioning and the Impact of Seizures in KBG Syndrome.

This study aimed to examine the adaptive functioning status and the impact of epileptic seizures on neurocognitive outcomes in KBG syndrome, a rare genetic neurodevelopmental disorder characterized by pathogenic variants in ANKRD11. A single clinician interviewed individuals and families with genetically confirmed cases of KBG syndrome. Trained professionals also conducted assessments using the Vineland-3 Adaptive Behavior Scales. The assessment covered the domains of communication, daily living skills, socialization, and maladaptive behaviors, and then compared individuals with and without epilepsy. Further comparisons were made with data from interviews and participants' medical records. Thirty-nine individuals (22 males, 17 females) with KBG syndrome, confirmed through genetic analysis, were interviewed via videoconferencing, followed by Vineland-3 assessment by trained raters. Individuals with KBG syndrome came from 36 unique families spanning 11 countries. While the KBG cohort displayed lower overall adaptive behavior composite scores compared with the average population, several members displayed standard scores at or higher than average, as well as higher scores compared with those with the neurodevelopmental disorder Ogden syndrome. Within the KBG cohort, males consistently scored lower than females across all domains, but none of these categories reached statistical significance. While the group with epilepsy exhibited overall lower scores than the nonseizure group in every category, statistical significance was only reached in the written communication subdomain. Our research provides insights that can aid in epilepsy screening and inform assessment strategies for neurocognitive functioning in those with this condition. The cohort performed overall higher than expected, with outliers existing in both directions. Although our results suggest that seizures might influence the trajectory of KBG syndrome, the approaching but overall absence of statistical significance between study groups underscores the need for a more extensive cohort to discern subtle variations in functioning.

A non-catalytic role of IPMK is required for PLCγ1 activation in T cell receptor signaling by stabilizing the PLCγ1-Sam68 complex.

BACKGROUND: Phospholipase C gamma 1 (PLCγ1) is an important mediator of the T cell receptor (TCR) and growth factor signaling. PLCγ1 is activated by Src family kinases (SFKs) and produces inositol 1,4,5-triphosphate (InsP3) from phosphatidylinositol 4,5-bisphosphate (PIP2). Inositol polyphosphate multikinase (IPMK) is a pleiotropic enzyme with broad substrate specificity and non-catalytic activities that mediate various functional protein-protein interactions. Therefore, IPMK plays critical functions in key biological events such as cell growth. However, the contribution of IPMK to the activation of PLCγ1 in TCR signaling remains mostly unelucidated. The current study aimed to elucidate the functions of IPMK in TCR signaling and to uncover the mode of IPMK-mediated signaling action in PLCγ1 activation. METHODS: Concanavalin A (ConA)-induced acute hepatitis model was established in CD4+ T cell-specific IPMK knockout mice (IPMKΔCD4). Histological analysis was performed to assess hepatic injury. Primary cultures of naïve CD4+ T cells were used to uncover the role of mechanisms of IPMK in vitro. Western blot analysis, quantitative real-time PCR, and flow cytometry were performed to analyze the TCR-stimulation-induced PLCγ1 activation and the downstream signaling pathway in naïve CD4+ T cells. Yeast two-hybrid screening and co-immunoprecipitation were conducted to identify the IPMK-binding proteins and protein complexes. RESULTS: IPMKΔCD4 mice showed alleviated ConA-induced acute hepatitis. CD4+ helper T cells in these mice showed reduced PLCγ1 Y783 phosphorylation, which subsequently dampens calcium signaling and IL-2 production. IPMK was found to contribute to PLCγ1 activation via the direct binding of IPMK to Src-associated substrate during mitosis of 68 kDa (Sam68). Mechanistically, IPMK stabilizes the interaction between Sam68 and to PLCγ1, thereby promoting PLCγ1 phosphorylation. Interfering this IPMK-Sam68 binding interaction with IPMK dominant-negative peptides impaired PLCγ1 phosphorylation. CONCLUSIONS: Our results demonstrate that IPMK non-catalytically promotes PLCγ1 phosphorylation by stabilizing the PLCγ1-Sam68 complex. Targeting IPMK in CD4+ T cells may be a promising strategy for managing immune diseases caused by excessive stimulation of TCR.

Effects of plant- and animal-based-protein meals for a day on serum nitric oxide and peroxynitrite levels in healthy young men.

Plant-based diets that replace animal-based proteins with plant-based proteins have received increased attention for cardiovascular protection. Nitric oxide (NO) plays an essential role in the maintenance of endothelial function. However, under higher oxidative stress, NO generation produces peroxynitrite, a powerful oxidant and vasoconstrictor. Diet-replaced protein sources has been reported to decrease oxidative stress. However, the effects of plant-based protein on NO and peroxynitrite have not yet been clarified. Therefore, this study aimed to compare the effects of plant- and animal-based-protein meals for a day on NO, peroxynitrite, and NO/peroxynitrite balance. A crossover trial of two meal conditions involving nine healthy men was performed. Participants ate standard meals during day 1. On day 2, baseline measurements were performed and the participants were provided with plant-based-protein meals or animal-based-protein meals. The standard and test meals consisted of breakfast, lunch, and dinner and were designed to be isocaloric. Plant-based-protein meals contained no animal protein. Blood samples were collected in the morning after overnight fasting before and after the test meals consumption. In the plant-based-protein meal condition, serum NOx levels (the sum of serum nitrite and nitrate) significantly increased, while serum peroxynitrite levels did not change significantly. Animal-based-protein meals significantly increased serum peroxynitrite levels but showed a trend of reduction in the serum NOx levels. Furthermore, serum NO/peroxynitrite balance significantly increased after plant-based-protein meals consumption, but significantly decreased after animal-based-protein meals consumption. These results suggest that, compared with animal-based-protein meals, plant-based-protein meals increase NO levels and NO/peroxynitrite balance, which reflects increased endothelial function.

Iconicity mediates semantic networks of sound symbolisma).

One speech sound can be associated with multiple meanings through iconicity, indexicality, and/or systematicity. It was not until recently that this "pluripotentiality" of sound symbolism attracted serious attention, and it remains uninvestigated how pluripotentiality may arise. In the current study, Japanese, Korean, Mandarin, and English speakers rated unfamiliar jewel names on three semantic scales: size, brightness, and hardness. The results showed language-specific and cross-linguistically shared pluripotential sound symbolism. Japanese speakers associated voiced stops with large and dark jewels, whereas Mandarin speakers associated [i] with small and bright jewels. Japanese, Mandarin, and English speakers also associated lip rounding with darkness and softness. These sound-symbolic meanings are unlikely to be obtained through metaphorical or metonymical extension, nor are they reported to colexify. Notably, in a purely semantic network without the mediation of lip rounding, softness can instead be associated with brightness, as illustrated by synesthetic metaphors such as yawaraka-na hizashi /jawaɾakanaçizaɕi/ "a gentle (lit. soft) sunshine" in Japanese. These findings suggest that the semantic networks of sound symbolism may not coincide with those of metaphor or metonymy. The current study summarizes the findings in the form of (phono)semantic maps to facilitate cross-linguistic comparisons of pluripotential sound symbolism.

Nonalcoholic fatty liver disease and accelerated loss of skeletal muscle mass: A longitudinal cohort study.

BACKGROUND AND AIMS: Whether subjects with NAFLD are at increased risk of sarcopenia is not well established. APPROACH AND RESULTS: This is a cohort study of 52,815 men and women of 20 years of age or older who underwent at least two health check-up exams with bioelectrical impedance analysis and abdominal ultrasound imaging. Bioelectrical impedance analysis was used to calculate appendicular skeletal muscle mass (ASM). NAFLD was assessed by ultrasonography, and its severity was assessed by the NAFLD fibrosis score (NFS). We estimated the 5-year change in ASM comparing participants with and without NAFLD at baseline using mixed linear models. The 5-year change in ASM in participants without and with NAFLD was -225.2 g (95% CI -232.3, -218.0) and -281.3 g (95% CI -292.0, -270.6), respectively (p < 0.001). In multivariable adjusted analysis, the difference in 5-year change in ASM comparing participants with and without NAFLD was -39.9 g (95% CI -53.1, -26.8). When participants with NAFLD were further divided by NAFLD severity, ASM loss was much faster in participants with NAFLD with intermediate to high NFS than in those with low NFS. CONCLUSIONS: Participants with NAFLD were at increased risk of sarcopenia, indicated by faster loss of skeletal muscle mass. Patients with NAFLD may need screening and early intervention to mitigate skeletal muscle mass loss.

Mechanisms underlying probiotic effects on neurotransmission and stress resilience in fish via transcriptomic profiling.

In recent years, studies have highlighted the significant impact of probiotic treatment on the central nervous system (brain) and stress regulation through the microbiota-gut-brain axis, yet there have been limited knowledge on this axis in fish. Therefore, this study aimed to enhance the current understanding of the mechanisms underlying probiotic effects on neurotransmission and stress alleviation in fish through transcriptomic profiling. In this study, olive flounders (Paralichthys olivaceus) were subjected to two trial setups: a 1-month lab-scale trial and a 6-month field-scale trial, with and without the probiotic strain Lactococcus lactis WFLU12. RNA-Seq analysis was performed using liver samples collected from fish at one-month post-feeding (mpf) in both trials. Additionally, fish growth was monitored monthly, and serological parameters were measured at one mpf in the field-scale experiment. The results of the lab-scale trial showed that probiotic administration significantly upregulated genes related to neurotransmission, such as htr3a, mao, ddc, ntsr1, and gfra2. These findings highlight the impact of probiotics on modulating neurotransmission via the microbiota-gut-brain axis. In the field-scale experiment, fish growth was significantly promoted and the sera levels of AST, LDH, and cortisol were significantly higher in the control group compared to the probiotics group. Furthermore, genes involved in stress responses (e.g. hsp70, hsp90B1, hspE1, prdx1, and gss) and transcriptional regulators (e.g. fos, dusp1, and dusp2) exhibited significant upregulation in the control group compared to the probiotics group, indicating that probiotic administration can alleviate stress levels in fish. Overall, this study provides valuable insights into the mechanisms underlying the beneficial effects of probiotics in fish, specifically regarding their impact on neurotransmission and stress alleviation.

Molecular mechanisms underlying the vulnerability of Pacific abalone (Haliotis discus hannai) to Vibrio harveyi infection at higher water temperature.

Climate change is one of the most important threats to farmed abalone worldwide. Although abalone is more susceptible to vibriosis at higher water temperatures, the molecular mode of action underlying this has not been fully elucidated. Therefore, this study aimed to address the high susceptibility of Halitotis discus hannai to V. harveyi infection using abalone hemocytes exposed to low and high temperatures. Abalone hemocytes were divided into four groups, 20C, 20 V, 25C, and 25 V, depending on co-culture with (V)/without (C) V. harveyi (MOI = 12.8) and incubation temperature (20 °C or 25 °C). After 3 h of incubation, hemocyte viability and phagocytic activity were measured, and RNA sequencing was performed using Illumina Novaseq. The expression of several virulence-related genes in V. harveyi was analyzed using real-time PCR. The viability of hemocytes was significantly decreased in the 25 V group compared to cells in the other groups, whereas phagocytic activity at 25 °C was significantly higher than at 20 °C. Although a number of immune-associated genes were commonly upregulated in abalone hemocyte exposed to V. harveyi, regardless of temperature, pathways and genes regarding pro-inflammatory responses (interleukin-17 and tumor necrosis factor) and apoptosis were significantly overexpressed in the 25 V group compared to the 25C group. Notably, in the apoptosis pathway, genes encoding executor caspases (casp3 and casp7) and pro-apoptotic factor, bax were significantly up-regulated only in the 25 V group, while the apoptosis inhibitor, bcl2L1 was significantly up-regulated only in the 20 V group compared to the control group at the respective temperatures. The co-culture of V. harveyi with abalone hemocytes at 25 °C up-regulated several virulence-related genes involved in quorum sensing (luxS), antioxidant activity (katA, katB, and sodC), motility (flgI), and adherence/invasion (ompU) compared to those at 20 °C. Therefore, our results showed that H. discus hannai hemocytes exposed to V. harveyi at 25 °C were highly stressed by vigorously activated inflammatory responses and that the bacterial pathogen overexpressed several virulence-related genes at the high temperature tested. The transcriptomic profile of both abalone hemocytes and V. harveyi in the present study provide insight into differential host-pathogen interactions depending on the temperature conditions and the molecular backgrounds related to increased abalone vulnerability upon global warming.

Molecular-level chemical composition of aerosol and its potential source tracking at Antarctic Peninsula.

Marine organic aerosols play crucial roles in global climatic systems. However, their chemical properties and relationships with various potential organic sources still need clarification. This study employed high-resolution mass spectrometry to investigate the identity, origin, and transportation of organic aerosols in pristine Antarctic environments (King Sejong Station; 62.2°S, 58.8°W), where complex ocean-cryosphere-atmosphere interactions occur. First, we classified the aerosol samples into three clusters based on their air mass transport history. Next, we investigated the relationship between organic aerosols and their potential sources, including organic matter dissolved in the open ocean, coastal waters, and runoff waters. Cluster 1 (C1), in which the aerosols mainly originated from the open ocean area (i.e., pelagic zone-influenced), exhibited a higher abundance of lipid-like and protein-like organic aerosols than cluster 3 (C3), with ratios 1.8- and 1.6-times higher, respectively. In contrast, C3, characterized by longer air mass retention over sea ice and land areas (i.e., inshore-influenced), had higher lignin- and condensed aromatic structures (CAS)-like organic aerosols by 2.2- and 3.4-times compared to C1. Cluster 2 (C2) has intermediate characteristics between C1 and C3 concerning the chemical properties of the aerosols and air mass travel history. Notably, the chemical properties of the aerosols assigned to C1 are closely related to those of phytoplankton-derived organics enriched in the open ocean. In contrast, those of C3 are comparable to those of terrestrial plant-derived organics enriched in coastal and runoff waters. These findings help evaluate the source-dependent properties of organic aerosols in changing Antarctic environment.

Nurses' Perceptions About Smart Beds in Hospitals.

The purpose of this study was to examine nurses' perceptions of the smart mattress equipped with Internet of things, which are incorporated into patients' beds. In addition, their concerns and suggestions about smart mattress were explored. A total of 349 nurses in a tertiary hospital participated in a cross-sectional survey. Data were collected using questionnaires. Descriptive statistical analysis was used for survey data, whereas content analysis was used for qualitative data from open-ended questions. The participants' intention to accept the smart mattresses was 12.5 (SD, 1.73) on average, indicating a high level of acceptance. The participants expected the smart mattresses to decrease their physical work burden, improve work efficiency, and prevent pressure ulcers. However, they were concerned about an increase in other aspects of their workload and in patient safety problems due to false alarms, inaccuracies, and malfunctions of the device. Nurses suggested various features that can be integrated into smart mattress. It is critical to address nurses' perceptions, expectations, and concerns during the conceptual and developmental stage of new technology in order to improve the usability, acceptance, and adoption of smart mattresses and other new innovations in hospital settings.

Association between body composition and chronic low back pain in Korean adults aged over 50 years: The Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2011.

Background The relationship between overweight or obesity and low back pain (LBP) has previously been investigated. Several recent studies have focused on the relationship between other indicators of obesity, particularly indicators of fat and the risk of LBP. However, the results of body composition and LBP have been inconsistent. Methods All data for the present retrospective, cross-sectional study was extracted from the Korea National Health and Nutrition Examination Survey (KNHANES) versions V-1 and 2 conducted in 2010 and 2011 by the Korean Centers for Disease Control and Prevention. In KNHANES V-1 (2010) and V-2 (2011), those over 50 years of age completed the surveys on LBP, body weight, and body composition assessed using dual-energy X-ray absorptiometry (DXA) were included. The multivariable logistic regression analysis was used to examine the relationship between the presence of chronic LBP and body composition adjusting for confounders. Results We analyzed 3,579 persons who completed the question. In the multivariable analyses adjusting for age and sex, none of the variables, including fat mass and fat-free mass, remained positively or negatively associated with LBP. Additionally, when depression, smoking, alcohol intake, physical activity, diabetes mellitus, and fat or lean tissue mass were included in the multivariable logistic model, no significant associations were found between all measures of fat mass, fat-free mass, and LBP Conclusion This study is contrary to previous studies that concluded that there is a correlation between obesity and fat mass and LBP. LBP is not associated with increased levels of obesity and fat mass.

Body Map of Droplet Distributions During Oropharyngeal Suction to Protect Health Care Workers From Airborne Diseases.

PURPOSE: Health care workers (HCWs), and in particular anesthesia providers, often must perform aerosol-generating medical procedures (AGMPs). However, no studies have analyzed droplet distributions on the bodies of HCWs during AGMPs. Therefore, the purpose of this study was to assess and analyze droplet distributions on the bodies of HCWs during suction of oral cavities with and without oral airways and during extubations. DESIGN: Using a quasi-experiemental design, we assumed the HCWs perform suction and extubation on intubated patients, and we prepared an intubated mannequin mimicking a patient. This study performed the oral suction and extubation on the intubated mannequin (with or without oral airways in place) and analyzed the droplet distributions. METHODS: We prepared a mannequin intubated with an 8.0 mm endotracheal tube, assuming the situation of general anesthesia. We designed the body mapping gown, and divided it into 10 areas including the head, neck, chest, abdomen, upper arms, forearms, and hands. We classified experiments into group O when suctions were performed on the mannequin with an oral airway, and into group X when the suctions were performed on the mannequin without an oral airway. An experienced board-certified anesthesiologist performed 10 oral suctions on each mannequin, and 10 extubations. We counted the droplets on the anesthesiologist's gown according to the divided areas after each procedure. FINDINGS: The mean droplet count after suction was 6.20 ± 2.201 in group O and 13.6 ± 4.300 in group X, with a significant difference between the two groups (P < .001). The right and left hands were the most contaminated areas in group O (2.8 ± 1.033 droplets and 2.0 ± 0.943 droplets, respectively). The abdomen, right hand, left forearm, and left hand showed many droplets in group X. (1.3 ± 1.337 droplets, 3.1 ± 1.792 droplets, 3.2 ± 3.910 droplets, and 4.3 ± 2.214 droplets, respectively). The chest, abdomen, and left hand presented significantly more droplets in group X than in group O. The trunk area (chest and abdomen) was exposed to more droplets during extubations than during suctions. CONCLUSIONS: During suctions, more droplets are splattered from mannequins without oral airways than from those with oral airways. The right and left hands were the most contaminated areas in group O. Moreover, the abdomen, right hand, left forearm, and left hand presented a lot of droplets in group X. In addition, extubations contaminate wider areas (the head, neck, chest and abdomen) of an HCW than suctions.

Dynamic Arterial Elastance as a Predictor of Supine-to-Prone Hypotension (SuProne Study): An Observational Study.

Background and Objectives: Supine-to-prone hypotension is caused by increased intrathoracic pressure and decreased venous return in the prone position. Dynamic arterial elastance (Eadyn) indicates fluid responsiveness and can be used to predict hypotension. This study aimed to investigate whether Eadyn can predict supine-to-prone hypotension. Materials and Methods: In this prospective, observational study, 47 patients who underwent elective spine surgery in the prone position were enrolled. Supine-to-prone hypotension is defined as a decrease in Mean Arterial Pressure (MAP) by more than 20% in the prone position compared to the supine position. Hemodynamic parameters, including systolic blood pressure (SAP), diastolic blood pressure, MAP, stroke volume variation (SVV), pulse pressure variation (PPV), stroke volume index, cardiac index, dP/dt, and hypotension prediction index (HPI), were collected in the supine and prone positions. Supine-to-prone hypotension was also assessed using two different definitions: MAPprone < 65 mmHg and SAPprone < 100 mmHg. Hemodynamic parameters were analyzed to determine the predictability of supine-to-prone hypotension. Results: Supine-to-prone hypotension occurred in 13 (27.7%) patients. Eadyn did not predict supine-to-prone hypotension [Area under the curve (AUC), 0.569; p = 0.440]. SAPsupine > 139 mmHg (AUC, 0.760; p = 0.003) and dP/dtsupine > 981 mmHg/s (AUC, 0.765; p = 0.002) predicted supine-to-prone hypotension. MAPsupine, SAPsupine, PPVsupine, and HPIsupine predicted MAPprone <65 mm Hg. MAPsupine, SAPsupine, SVVsupine, PPVsupine, and HPIsupine predicted SAPprone < 100 mm Hg. Conclusions: Dynamic arterial elastance did not predict supine-to-prone hypotension in patients undergoing spine surgery. Systolic arterial pressure > 139 mmHg and dP/dt > 981 mmHg/s in the supine position were predictors for supine-to-prone hypotension. When different definitions were employed (mean arterial pressure < 65 mmHg in the prone position or systolic arterial pressure < 100 mmHg in the prone position), low blood pressures in the supine position were related to supine-to-prone hypotension.

Simultaneous measurement of OH radical, H2O concentration, and temperature in a premixed CH4/air flame using TDLAS with an improved analysis method.

The OH radical concentration was measured by applying tunable diode laser absorption spectroscopy, which is an in situ optical method. An optical absorption region (P7.5ff transition at 1502.7 nm) of the OH radical was selected in the near-infrared range to measure the OH radicals quantitatively in premixed CH4/air flames. An improved direct absorption spectroscopy (DAS) method based on wavelength division multiplexing was proposed to extract the H2O absorption signal that interfered with the OH light absorption signal, and the integral intensity of OH* chemiluminescence was compared to the measured OH radical concentration based on the improved DAS method.

Mesoporous platinum nanoparticles as a peroxidase mimic for the highly sensitive determination of C-reactive protein.

The generation of a mesoporous structure in platinum nanoparticles can effectively enhance physical and chemical properties. In this study, mesoporous platinum nanoparticles (MPNs) were synthesized by a soft template-mediated one-pot chemical method. To develop a mesoporous structure, Pluronic F-127 was employed. The Pluronic F-127 surfactant forms self-assembled micelles, and the micelles act as the pore-directing agents in the synthesis of nanoparticles. Scanning electron microscopy results revealed that the MPN had a uniform size of 70 nm on average and a distinct mesoporous structure. The development of a concave mesoporous structure on the surface of the MPNs can increase the surface area and facilitate the efficient transport of reactants. The synthesized MPNs exhibited peroxidase-like activity. Furthermore, the MPNs showed excellent catalytic efficiency compared to HRP, due to the high surface area derived from the presence of the mesoporous structure. The peroxidase-like MPNs were applied to the enzyme-linked immunosorbent assay (ELISA) of C-reactive protein (CRP). The MPN-based ELISA exhibited sensitive CRP detection in the range from 0.24 to 7.8 ng/mL with a detection limit of 0.13 ng/mL. Moreover, the recoveries of the CRP concentrations in spiked human serum were 98.6% and 102%. These results demonstrate that as a peroxidase mimic, the MPNs can replace the natural enzymes in conventional ELISA for sensitive CRP detection.

Management of chimeric antigen receptor T-cell induced cytokine release syndrome: Current and emerging approaches.

The most common adverse event associated with chimeric antigen receptor T-cell therapy is cytokine release syndrome, which is characterized by fever, hypoxia, and hypotension in varying degrees of severity. In severe cases, cytokine release syndrome can result in life-threatening symptoms such as multi-organ failure. The widely accepted first-line therapy for cytokine release syndrome management is tocilizumab with or without corticosteroids, but there is very limited guidance on the proper management of patients unresponsive to this regimen. There are emerging strategies that target cytokine release syndrome through novel mechanisms, showing promise in treating or preventing severe cytokine release syndrome. Although further clinical investigation is necessary to assess the applicability of the emerging approaches, these exploratory therapies may shape the future landscape of chimeric antigen receptor T-cell induced cytokine release syndrome management. This review article provides a comprehensive overview of the current and emerging therapies for the management of chimeric antigen receptor T-cell induced cytokine release syndrome, especially cases that are refractory to tocilizumab and steroids.

Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines.

BACKGROUND: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. OBJECTIVE: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). METHODS: The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. RESULTS: PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1+/- AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of TH2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinase-dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. CONCLUSIONS: PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.

Subscapularis-sparing deltopectoral approach in reverse total shoulder arthroplasty.

PURPOSE: This study compared the clinical and radiologic results of reverse shoulder arthroplasty (RSA) using either the subscapularis-sparing deltopectoral approach (SSDA) or traditional deltopectoral approach (TDA) in cuff tear arthropathy patients. MATERIALS AND METHOD: We retrospectively evaluated 71 patients who underwent RSA for cuff tear arthropathy between July 2014 and December 2018. Patients were divided into two groups according to the surgical approach: TDA (34 cases) and SSDA (37 cases). The mean patient age was 78.6 years, and the mean (range) follow-up period was 23.5 (12-48) months. Clinical results were assessed using the Visual Analogue pain Scale (VAS), American Shoulder and Elbow Surgeon score (ASES), Korean Shoulder Scoring System (KSS), and Constant score. Radiographic indicators prosthesis-scapular neck angle (PSNA), peg-glenoid rim distance (PGRD), inferior overhang, acromion-greater tuberosity (AT) distance, and glenoid-greater tuberosity (GT) distance) were assessed, and notching severity was assessed according to the Nerot-Sirveaux classification. RESULTS: The radiographic indicator results of the TDA and SSDA groups were as follows: PSNA (131.4° ± 17.2°, 136.1° ± 7.7°), PGRD (18.7 mm ± 2.9 mm, 21.4 mm ± 2.0 mm), AT distance (38.3 mm ±6.9 mm, 37.5 mm ± 6.8 mm), GT distance (51.6 mm ± 6.3 mm, 51.4 mm ± 5.3 mm), and inferior overhang (4.4 mm ± 2.2 mm, 2.9 mm ± 1.3 mm). PGRD and inferior overhang showed statistically significant differences between groups, but the clinical results showed no significant differences. There were no complications such as neurovascular injury, implant loosening, surgical site infection, or acromion fracture in either group. CONCLUSION: SSDA for RSA showed no significant differences in clinical and radiological results compared with TDA. Therefore, SSDA is a viable alternative for RSA in cuff tear arthropathy.