Ventral pallidum GABA and glutamate neurons drive approach and avoidance through distinct modulation of VTA cell types.

The ventral pallidum (VP) contains GABA and glutamate neurons projecting to ventral tegmental area (VTA) whose stimulation drives approach and avoidance, respectively. Yet little is known about the mechanisms by which VP cell types shape VTA activity and drive behavior. Here, we found that both VP GABA and glutamate neurons were activated during approach to reward or by delivery of an aversive stimulus. Stimulation of VP GABA neurons inhibited VTA GABA, but activated dopamine and glutamate neurons. Remarkably, stimulation-evoked activation was behavior-contingent such that VTA recruitment was inhibited when evoked by the subject's own action. Conversely, VP glutamate neurons activated VTA GABA, as well as dopamine and glutamate neurons, despite driving aversion. However, VP glutamate neurons evoked dopamine in aversion-associated ventromedial nucleus accumbens (NAc), but reduced dopamine release in reward-associated dorsomedial NAc. These findings show how heterogeneous VP projections to VTA can be engaged to shape approach and avoidance behaviors.

How should I approach and manage adult-onset oscillopsia?

Oscillopsia is the sensation of illusory movement within the visual percept leading to a degradation of visual functioning and quality of life. The constellation of conditions manifesting with oscillopsia marks the overlap between ophthalmology and otorhinolaryngology. The purpose of this article is therefore to review the aetiologies of oscillopsia and provide pathways for investigation and treatment of processes that associate oscillopsia with intrusive ocular movement and for processes manifesting as oscillopsia in the absence of intrusive ocular movement. Points for referral are also included for the diagnoses that are more appropriately investigated and managed by allied medical specialties.

Mycoplasma genitalium infection and resistance-associated mutations to macrolides and fluoroquinolones among high-risk patients in Taiwan.

BACKGROUND: Mycoplasma genitalium is an emerging etiology of sexually transmitted infections (STIs) with increasing resistance to antimicrobials. Surveillance on the epidemiology of M. genitalium infection and antimicrobial resistance is warranted. METHODS: Between September 2021 and August 2023, people with HIV (PWH) and people without HIV (PWoH) at risk of STIs were screened for M. genitalium infection using a multiplex polymerase-chain-reaction assay of specimens collected from the rectum, urethra, oral cavity, and vagina. The prevalences of resistance-associated mutations (RAMs) of M. genitalium to fluoroquinolones, macrolides, and tetracycline were investigated. RESULTS: During the 2-year study period, 1021 participants were enrolled, including 531 PWH and 490 PWoH. Overall, 83 (8.1%) and 34 (7.6%) participants had M. genitalium infection at baseline and during follow-up, respectively, with the rectum being the most common site of detection (61.5%). With the first course of antimicrobial treatment, 27 of 63 (42.9%) participants with M. genitalium infection were cured during follow-up, including 24 of 58 (41.4%) who received doxycycline monotherapy. The prevalence of RAMs to macrolides, fluoroquinolones, and tetracyclines at baseline were 24.3%, 22.4%, and 7.9%, respectively. Though PWH had more M. genitalium infection (10.2% vs 5.9%, p = 0.01), a higher rate of RAMs to macrolides (41.0% vs 14.7%, p < 0.01) was found in PWoH. CONCLUSIONS: Among high-risk populations, the prevalence of M. genitalium infection was 8.1%. The overall genotypic resistance of M. genitalium to macrolides and fluoroquinolones was moderately high in Taiwan. Detection of M. genitalium infection and antimicrobial resistance is warranted to ensure resistance-guided antimicrobial treatments to be administered.

Sexually transmitted coinfections among at-risk HIV-positive MSM: implications for optimal preemptive treatment.

Background: Concurrent sexually transmitted infections (STIs) are common in sexually active populations. We aimed to estimate the prevalence and coinfection rates of bacterial STIs among sexually active, HIV-positive men who have sex with men (MSM), and to assess the potential benefits of different combination treatment regimens in managing concurrent bacterial STIs. Methods: From September 2021 to September 2023, HIV-positive MSM underwent STI testing when they had symptoms suggestive of STIs or recently acquired hepatitis C virus (HCV) infection or early syphilis. The oral rinse, rectal swab, and urethral swab specimens were tested for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma spp., Ureaplasma spp., and Trichomonas vaginalis with the use of multiplex real-time polymerase-chain-reaction assays. The estimated coinfection rates were used to evaluate the benefits of different combination treatment regimens for managing coinfections. Results: During the study period, 535 participants (median age, 37 years; and CD4 count, 615 cells/mm3) were enrolled. On their first visits, at least one bacterial pathogen was detected in 57.9% and concomitant bacterial infections were found in 32.9% of the participants. The most commonly identified pathogen was U. urealyticum (36.3%), followed by C. trachomatis (22.8%), and N. gonorrhoeae (19.8%). The factors associated with any bacterial STIs included older age (per 1-year increase, adjusted odds ratio [AOR], 0.97; 95% confidence interval [CI], 0.95-1.00), early syphilis (AOR, 1.87; 95% CI, 1.22-2.84), and having more than 5 sex partners in the preceding 3 months (AOR, 2.08, 95% CI, 1.07-4.06). A combination therapy of benzathine penicillin G with a 7-day course of doxycycline could simultaneously treat 27.1% of C. trachomatis coinfections in participants with early syphilis, while a combination therapy of ceftriaxone with doxycycline could simultaneously treat 40.6% of chlamydial coinfections in participants with gonorrhea. Conclusion: Bacterial STIs were prevalent and concomitant infections were not uncommon among sexually active, HIV-positive MSM, supporting regular screening for bacterial STIs. The effectiveness of preemptive use of doxycycline as combination therapy for concurrent STIs warrants more investigations.

Increasing Preterm Delivery and Small for Gestational Age Trends in South Carolina during the COVID-19 Pandemic.

Preterm delivery (PTD) complications are a major cause of childhood morbidity and mortality. We aimed to assess trends in PTD and small for gestational age (SGA) and whether trends varied between race-ethnic groups in South Carolina (SC). We utilized 2015-2021 SC vital records linked to hospitalization and emergency department records. PTD was defined as clinically estimated gestation less than (<) 37 weeks (wks.) with subgroup analyses of PTD < 34 wks. and < 28 wks. SGA was defined as infants weighing below the 10th percentile for gestational age. This retrospective study included 338,532 (243,010 before the COVID-19 pandemic and 95,522 during the pandemic) live singleton births of gestational age ≥ 20 wks. born to 260,276 mothers in SC. Generalized estimating equations and a change-point during the first quarter of 2020 helped to assess trends. In unadjusted analyses, pre-pandemic PTD showed an increasing trend that continued during the pandemic (relative risk (RR) = 1.04, 95% CI: 1.02-1.06). PTD < 34 wks. rose during the pandemic (RR = 1.07, 95% CI: 1.02-1.12) with a significant change in the slope. Trends in SGA varied by race and ethnicity, increasing only in Hispanics (RR = 1.02, 95% CI: 1.00-1.04) before the pandemic. Our study reveals an increasing prevalence of PTD and a rise in PTD < 34 wks. during the pandemic, as well as an increasing prevalence of SGA in Hispanics during the study period.

Using Virtual Reality in a Rehabilitation Program for Patients With Breast Cancer: Phenomenological Study.

Background: Surgery is an essential treatment for early-stage breast cancer. However, various side effects of breast cancer surgery, such as arm dysfunction and lymphedema, remain causes for concern. Rehabilitation exercises to prevent such side effects should be initiated within 24 hours after surgery. Virtual reality (VR) can assist the process of rehabilitation; however, the feasibility of applying VR for rehabilitation must be explored, in addition to experiences of this application. Objective: This study explored patients' attitudes toward and experiences of using VR for their rehabilitation to determine the feasibility of such VR use and to identify potential barriers. Methods: A phenomenological qualitative study was conducted from September to December 2021. A total of 18 patients with breast cancer who had undergone surgical treatment were interviewed using open-ended questions. The Colaizzi 7-step procedure for phenomenological analysis was used for data analysis. To ensure high study reliability, this study followed previously reported quality criteria for trustworthiness. Results: Three themes were identified: (1) VR was powerful in facilitating rehabilitation, (2) early and repetitive upper limb movements were an advantage of VR rehabilitation, and (3) extensive VR use had challenges to be overcome. Most of the interviewed patients reported positive experiences of using VR for rehabilitation. Specifically, VR helped these patients identify appropriate motion and angle limits while exercising; in other words, knowledge gained through VR can play a key role in the rehabilitation process. In addition, the patients reported that the use of VR provided them company, similar to when a physiotherapist is present. Finally, the gamified nature of the VR system seemed to make VR-based rehabilitation more engaging than traditional rehabilitation, particularly with respect to early rehabilitation; however, the high cost of VR equipment made VR-based rehabilitation difficult to implement at home. Conclusions: The interviewed patients with breast cancer had positive experiences in using VR for rehabilitation. The high cost of both VR equipment and software development presents a challenge for applying VR-based rehabilitation.

Proteomic Analysis of Lysine Acetylation and Succinylation to Investigate the Pathogenicity of Virulent Pseudomonas syringae pv. tomato DC3000 and Avirulent Line Pseudomonas syringae pv. tomato DC3000 avrRpm1 on Arabidopsis thaliana.

Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is able to infect many economically important crops and thus causes substantial losses in the global agricultural economy. Pst DC3000 can be divided into virulent lines and avirulent lines. For instance, the pathogen effector avrRPM1 of avirulent line Pst-avrRpm1 (Pst DC3000 avrRpm1) can be recognized and detoxified by the plant. To further compare the pathogenicity mechanisms of virulent and avirulent Pst DC3000, a comprehensive analysis of the acetylome and succinylome in Arabidopsis thaliana was conducted following infection with virulent line Pst DC3000 and avirulent line Pst-avrRpm1. In this study, a total of 1625 acetylated proteins encompassing 3423 distinct acetylation sites were successfully identified. Additionally, 229 succinylated proteins with 527 unique succinylation sites were detected. A comparison of these modification profiles between plants infected with Pst DC3000 and Pst-avrRpm1 revealed significant differences. Specifically, modification sites demonstrated inconsistencies, with a variance of up to 10% compared to the control group. Moreover, lysine acetylation (Kac) and lysine succinylation (Ksu) displayed distinct preferences in their modification patterns. Lysine acetylation is observed to exhibit a tendency towards up-regulation in Arabidopsis infected with Pst-avrRpm1. Conversely, the disparity in the number of Ksu up-regulated and down-regulated sites was not as pronounced. Motif enrichment analysis disclosed that acetylation modification sequences are relatively conserved, and regions rich in polar acidic/basic and non-polar hydrophobic amino acids are hotspots for acetylation modifications. Functional enrichment analysis indicated that the differentially modified proteins are primarily enriched in the photosynthesis pathway, particularly in relation to light-capturing proteins. In conclusion, this study provides an insightful profile of the lysine acetylome and succinylome in A. thaliana infected with virulent and avirulent lines of Pst DC3000. Our findings revealed the potential impact of these post-translational modifications (PTMs) on the physiological functions of the host plant during pathogen infection. This study offers valuable insights into the complex interactions between plant pathogens and their hosts, laying the groundwork for future research on disease resistance and pathogenesis mechanisms.

Comparative analysis of sipeimine content, metabolome and chloroplast genome in cultivated and wild varieties of Fritillaria taipaiensis.

BACKGROUND: The wild variety Fritillaria taipaiensis E.B (EB) is known for its superior therapeutic effects, but its limited production cannot meet demand. As a result, the cultivated variety F. taipaiensis P. Y. Li (PY) has been widely grown. In this study, we conducted a comprehensive analysis comparing EB and PY in terms of external features, sipeimine content, metabolome and chloroplast genome to differentiate these two varieties. RESULTS: Our research revealed that the petals and pods of EB are green, while those of PY have purple markings. The bulbs of EB contain significantly higher levels of sipeimine compared to those of PY. Metabolomic analysis identified 56 differentially expressed metabolites (DMs), with 23 upregulated and 33 downregulated in EB bulbs. Particularly, 3-hydroxycinnamic acid and secoxyloganin may serve as distinctive DMs. These DMs were associated with 17 KEGG pathways, including pyrimidine metabolism, alanine, aspartate and glutamate metabolism, and galactose metabolism. Differences in the length of the chloroplast genome were primarily observed in the large single-copy (LSC) region, with the largest variation in the trnH-GUC-psbA region. The placement of the trnH gene and the rps gene in proximity to the LSC/IRb boundary differs between EB and PY. CONCLUSION: The results of this study provide valuable insights for the introduction and comprehensive development of wild F. taipaiensis from a scientific perspective. © 2024 Society of Chemical Industry.

Two-dimensional monolayer C5-10-16: a metallic carbon allotrope as an anode material for high-performance sodium/potassium-ion batteries.

Carbonaceous materials are promising candidates as anode materials for non-lithium-ion batteries (NLIBs) due to their appealing properties such as good electrical conductivity, low cost, and high safety. However, graphene, a classic two-dimensional (2D) carbon material, is chemically inert to most metal atoms, hindering its application as an electrode material for metal-ion batteries. Inspired by the unique geometry of a four-penta unit, we explore a metallic 2D carbon allotrope C5-10-16 composed of 5-10-16 carbon rings. The C5-10-16 monolayer is free from any imaginary frequencies in the whole Brillouin zone. Due to the introduction of a non-sp2 hybridization state into C5-10-16, the extended conjugation of π-electrons is disrupted, leading to the enhanced surface activity toward metal ions. We investigate the performance of C5-10-16 as the anode for sodium/potassium-ion batteries by using first-principles calculations. The C5-10-16 sheet has high theoretical specific capacities of Na (850.84 mA h g-1) and K (743.87 mA h g-1). Besides, C5-10-16 exhibits a moderate migration barrier of 0.63 (0.32) eV for Na (K), ensuring rapid charging/discharging processes. The average open-circuit voltages of Na and K are 0.33 and 0.62 V, respectively, which are within the voltage acceptance range of anode materials. The fully sodiated (potassiated) C5-10-16 shows tiny lattice expansions of 1.4% (1.3%), suggesting the good reversibility. Moreover, bilayer C5-10-16 significantly affects both the adsorption strength and the mobility of Na or K. All these results show that C5-10-16 could be used as a promising anode material for NLIBs.

A 12-week randomized double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine.

Omega-3 polyunsaturated fatty acids (PUFAs) may benefit migraine improvement, though prior studies are inconclusive. This study evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine (EM) prevention. Seventy individuals with EM participated in a 12-week randomized, double-blind, placebo-controlled trial from March 2020 and May 2022. They were randomly assigned to either the EPA (N = 35, 2 g fish oil with 1.8 g of EPA as a stand-alone treatment daily), or the placebo group (N = 35, 2 g soybean oil daily). Migraine frequency and headache severity were assessed using the monthly migraine days, visual analog scale (VAS), Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and Pittsburgh Sleep Quality Index (PSQI) in comparison to baseline measurements. The EPA group significantly outperformed the placebo in reducing monthly migraine days (-4.4 ± 5.1 days vs. - 0.6 ± 3.5 days, p = 0.001), days using acute headache medication (-1.3 ± 3.0 days vs. 0.1 ± 2.3 days, p = 0.035), improving scores for headache severity (ΔVAS score: -1.3 ± 2.4 vs. 0.0 ± 2.2, p = 0.030), disability (ΔMIDAS score: -13.1 ± 16.2 vs. 2.6 ± 20.2, p = 0.001), anxiety and depression (ΔHADS score: -3.9 ± 9.4 vs. 1.1 ± 9.1, p = 0.025), and quality of life (ΔMSQ score: -11.4 ± 19.0 vs. 3.1 ± 24.6, p = 0.007). Notably, female particularly benefited from EPA, underscoring its potential in migraine management. In conclusion, high-dose EPA has significantly reduced migraine frequency and severity, improved psychological symptoms and quality of life in EM patients, and shown no major adverse events, suggesting its potential as a prophylactic for EM.

Neuron-derived neurotensin promotes pancreatic cancer invasiveness and gemcitabine resistance via the NTSR1/Akt pathway.

Perineural invasion and neurogenesis are frequently observed in pancreatic ductal adenocarcinoma (PDAC) and link to poor outcome. However, how neural factors affect PDAC prognosis and the underlying mechanism as well as counteracting therapeutic are still unclear. In silico systematic analysis was performed with PROGgene to identify potential neural factor and its receptor in pancreatic cancer. In vitro assays including migration, invasion, 3D recruitment, and gemcitabine resistance were performed to study the effect of neuron-derived neurotensin (NTS) on pancreatic cancer behavior. Orthotopic animal study was used to validate the in vitro findings. Gene set enrichment analysis (GSEA) was performed to confirm the results from in silico to in vivo. Expression of NTS and its receptor 1 (NTSR1) predicted poor prognosis in PDAC. NTS synthetic peptide or neuron-derived condition medium promoted pancreatic cancer invasiveness and recruitment in 2D and 3D assays. NTS-induced effects depended on NTSR1 and PI3K activation. GDC-0941, a clinically approved PI3K inhibitor, counteracted NTS-induced effects in vitro. Inhibition of NTSR1 in pancreatic cancer cells resulted in decreased tumor dissemination and diminished PI3K activation in vivo. NTS boosted gemcitabine resistance via NTSR1 in pancreatic cancer. Our results suggest that neural cell-secreted NTS plays an important role in promoting PDAC.

Unravelling the Role of Free Radicals in Photocatalysis.

Free radicals are increasingly recognized as active intermediate reactive species that can participate in various redox processes, significantly influencing the mechanistic pathways of reactions. Numerous researchers have investigated the generation of one or more distinct photogenerated radicals, proposing various hypotheses to explain the reaction mechanisms. Notably, recent research has demonstrated the emergence of photogenerated radicals in innovative processes, including organic chemical reactions and the photocatalytic dissolution of precious metals. To harness the potential of these free radicals more effectively, it is imperative to consolidate and analyze the processes and action modes of these photogenerated radicals. This conceptual paper delves into the latest advancements in understanding the mechanics of photogenerated radicals.

Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

Risk factors of early disease progression and decreased survival for multiple myeloma patients after upfront autologous stem cell transplantation.

Multiple myeloma (MM) stands as the second most prevalent hematological malignancy, constituting approximately 10% of all hematological malignancies. Current guidelines recommend upfront autologous stem cell transplantation (ASCT) for transplant-eligible MM patients. This study seeks to delineate factors influencing post-ASCT outcomes in MM patients. Our cohort comprised 150 MM patients from Taipei Veterans General Hospital, with progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint. A Cox proportional hazards model was employed to discern potential predictive factors for survival. ASCT age ≥ 65 (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.08-3.47) and the presence of extramedullary disease (HR 2.53, 95% CI 1.53-4.19) negatively impacted PFS. Conversely, treatment response ≥ VGPR before ASCT (HR 0.52, 95% CI 0.31-0.87) and total CD34+ cells collected ≥ 4 × 106 cells/kg on the first stem cell harvesting (HR 0.52, 95% CI 0.32-0.87) were positively associated with PFS. For OS, patients with ISS stage III (HR 2.06, 95% CI 1.05-4.04), the presence of extramedullary disease (HR 3.92, 95% CI 2.03-7.58), light chain ratio ≥ 100 before ASCT (HR 7.08, 95% CI 1.45-34.59), post-ASCT cytomegalovirus infection (HR 9.43, 95% CI 3.09-28.84), and a lower conditioning melphalan dose (< 140 mg/m2; HR 2.75, 95% CI 1.23-6.17) experienced shorter OS. In contrast, post-ASCT day + 15 absolute monocyte counts (D15 AMC) > 500/µl (HR 0.36, 95% CI 0.17-0.79) and post-ASCT day + 15 platelet counts (D15 PLT) > 80,000/µl (HR 0.48, 95% CI 0.24-0.94) were correlated with improved OS. Significantly, early PLT and AMC recovery on day + 15 predicting longer OS represents a novel finding not previously reported. Other factors also align with previous studies. Our study provides real-world insights for post-ASCT outcome prediction beyond clinical trials.

Effectiveness and evolution of anti-SARS-CoV-2 spike protein titers after three doses of COVID-19 vaccination in people with HIV.

BACKGROUND: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). METHODS: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-µg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. RESULTS: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-µg mRNA-1273, 467 (32.8%) 50-µg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-µg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). CONCLUSIONS: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-µg mRNA-1273 could generate a higher antibody response than with 50-µg mRNA-1273 and BNT162b2 vaccine.

Molecular characterization of a carbon dioxide-dependent Proteus mirabilis small-colony variant isolated from a clinical specimen.

INTRODUCTION: Carbon dioxide-dependent Proteus mirabilis has been isolated from clinical specimens. It is not clear whether mutations in carbonic anhydrase are responsible for the carbon dioxide dependence of P. mirabilis. The pathogenicity of carbon dioxide-dependent P. mirabilis also remains unclear. The purpose of this study was to determine the cause carbon dioxide dependence of P. mirabilis and its pathogenicity. METHODS: The DNA sequence of can encoding carbonic anhydrase of a carbon dioxide-dependent P. mirabilis small colony variant (SCV) isolate was analyzed. To confirm that impaired carbonic anhydrase activity is responsible for the formation of the carbon dioxide-dependent SCV phenotype of P. mirabilis, we performed complementation experiments using plasmids with intact can. Additionally, mouse infection experiments were performed to confirm the change in virulence due to the mutation of carbonic anhydrase. RESULTS: We found that the can gene of the carbon dioxide-dependent P. mirabilis SCV isolate showed had a frameshift mutation with a deletion of 1 bp (c. 173delC). The can of P. mirabilis encodes carbonic anhydrase was also found to function in Escherichia coli. The cause of the carbon dioxide-dependent SCV phenotype of P. mirabilis was an abnormality in carbonic anhydrase. Nevertheless, no changes were observed in virulence due to the mutation of carbonic anhydrase in mouse infection experiments. CONCLUSIONS: The can gene is essential for the growth of P. mirabilis in ambient air. The mechanisms underlying this fitness advantage in terms of infection warrant further investigation.

Comparing transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets: an analysis using propensity score matching.

Transfusion reactions induced by platelet transfusions may be reduced and alleviated by leukocyte reduction of platelets. Although leukoreduction of apheresis platelets can be performed either pre-storage or post-storage, seldom studies directly compare the incidence of transfusion reaction in these two different blood products. We conducted a retrospective study to compare the transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets. We reviewed the general characteristics and the transfusion reactions, symptoms, and categories for inpatients who received pre-storage or post-storage leukoreduced apheresis platelets. Propensity-score matching was performed to adjust for baseline differences between groups. A total of 40,837 leukoreduction apheresis platelet orders were reviewed. 116 (0.53%) transfusion reactions were reported in 21,884 transfusions with pre-storage leukoreduction, and 174 (0.91%) reactions were reported in 18,953 transfusions with post-storage leukoreduction. Before propensity-score matching, the odds ratio for transfusion reactions in the pre-storage group relative to the post-storage group was 0.57 (95% confidence interval [CI] 0.45-0.72, P < 0.01); the odds ratio after matching was 0.63 (95% CI 0.49-0.80, P < 0.01). A two-proportion z-test revealed pre-storage leukoreduction significantly decreases the symptoms of chills, fever, itching, urticaria, dyspnea, and hypertension as compared with those in post-storage leukoreduction. Pre-storage leukoreduced apheresis platelet significantly decreased febrile non-hemolytic transfusion reaction as compared with post-storage groups. This study suggests pre-storage leukoreduction apheresis platelet significantly decreases the transfusion reaction as compared with those in post-storage leukoreduction.

LC-MS/MS analysis of Shenghui decoction component and its effect on learning and memory and neuroprotection in sleep deprivation model mice.

BACKGROUND: In recent years, sleep problems have emerged as a significant factor in the development of diseases that influence cognitive function. The inflammatory response may have a role in the neurobiological processes of sleep deprivation, resulting in impairment of memory and learning. Shenghui Decoction (SHD) is a classic formula in Chinese medicine used to treat forgetfulness and insomnia. However, it remains unclear whether the anti-inflammatory effects of SHD are specifically linked to the inhibition of P2X7R and p38MAPK. METHODS: Analysis of chemical constituents of Shenghui Decoction based on UPLC-Q-TOF-MS / MS. The learning and memory competency of the mice was assessed using the new object recognition and Morris water maze tests. The morphology of hippocampus neurons was observed using HE staining, and the expression of inflammatory factors was measured using ELISA and immunofluorescence. The expression of P2X7R and p38MAPK in the hippocampus was analyzed via real-time PCR and Western blotting. Additionally, the components absorbed into the bloodstream of SHD were analyzed. RESULTS: The study found that SHD contains 47 chemical constituents, including phenolic acids, flavonoids, iridoids, and triterpenoids. In addition, it was observed that SHD significantly improved the learning and memory abilities of the mice. SHD also improved the morphology of hippocampus neurons. The expression of inflammatory factors was decreased in the SHD-treated mice. Additionally, the expression of P2X7R and p38MAPK was decreased in the hippocampus of the SHD-treated mice. Fifteen prototype chemical constituents were detected in blood. CONCLUSIONS: The study suggests that SHD could be a viable treatment for cognitive impairments associated with brain inflammation. The therapeutic effects of SHD are likely due to its chemical components, including phenolic acids, flavonoids, iridoids, and triterpenoids. SHD can improve learning and memory impairment caused by sleep deprivation through the P2X7R/p38MAPK inflammatory signaling pathways.

RNF43 Inactivation Enhances the B-RAF/MEK Signaling and Creates a Combinatory Therapeutic Target in Cancer Cells.

RING finger 43 (RNF43), a RING-type E3 ubiquitin ligase, is a key regulator of WNT signaling and is mutated in 6-10% of pancreatic tumors. However, RNF43-mediated effects remain unclear, as only a few in vivo substrates of RNF43 are identified. Here, it is found that RNF43-mutated pancreatic cancer cells exhibit elevated B-RAF/MEK activity and are highly sensitive to MEK inhibitors. The depletion of RNF43 in normal pancreatic ductal cells also enhances MEK activation, suggesting that it is a physiologically regulated process. It is confirmed that RNF43 ubiquitinates B-RAF at K499 to promote proteasome-dependent degradation, resulting in reduced MEK activity and proliferative ability in cancer cells. In addition, phosphorylation of B-RAF at T491 suppresses B-RAF ubiquitination by decreasing the interaction between RNF43 and B-RAF. Mutations at K499 in B-RAF are identified in various cancer types. MEK and WNT inhibitors synergistically suppress the growth of RNF43-mutated pancreatic cancer cells in vitro and in vivo. Collectively, the research reveals a novel mechanism by which RNF43 inhibits B-RAF/MEK signaling to suppress tumor growth and provide a new strategy for the treatment of RNF43-inactivated pancreatic cancer.

Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005-2018.

Background: This retrospective study aimed to determine the risk of venous thromboembolism (VTE) in patients with PsA after surgery for lumbar degenerative disease (LDD). Methods: The study data of adults aged ≥20 years admitted to U.S. hospitals with diagnoses of LDD and undergoing spinal decompression or fusion between 2005 and 2018 were extracted from the National Inpatient Sample (NIS) database. Patients were further divided into two groups based on a diagnosis of PsA or not via codes ICD-9: 696.0 and ICD-10: L40.50. Patients with missing information were excluded. Propensity score matching (PSM) was employed to enhance comparability between groups. Logistic regression was used to determine associations between PsA and various outcomes, including complications, unfavorable discharge, and prolonged length of stay (LOS). Results: Data on 471,283 patients with LDD was extracted from the NIS database.from 2005 to 2018. Before propensity score matching, patients with PsA had higher proportions of overall morbidity (8.8 % vs. 6.9 %), VTE (1.4 % vs. 0.7 %), and unfavorable discharge (20.8 % vs. 16.9 %). After matching, patients with PsA still had higher VTE incidence and unfavorable discharge proportions. After adjustments, multivariable regression analysis indicated that patients with PsA had a higher risk of unfavorable discharge (aOR: 1.26, 95 % CI: 1.03-1.55) and VTE (aOR: 1.99, 95 % CI: 1.05-3.75). Conclusions: Among patients undergoing surgery for LDD, pre-existing PsA may be associated with increased risks of unfavorable discharge and VTE occurrence. The findings may benefit preoperative risk stratifications before LDD surgeries.