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Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org).

Objectives: This study compared the prevalence and odds of mental health service utilization among people of Asian ancestry with lifetime DSM-IV mood, anxiety, alcohol, and drug use disorders with utilization by members of other racial and ethnic groups with similar disorders.Methods: Between 2001 and 2002, a total of 43,093 noninstitutionalized individuals were assessed by the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) study of lifetime prevalence of DSM-IV psychiatric disorders and mental health service utilization among various ethnic and racial groups.Results: Among individuals with lifetime mood disorders, Asians had significantly lower mental health service utilization compared with whites (odds ratio [OR]=.31, 95% confidence interval [CI]=.21-.46), Hispanics (OR=.49, CI=.33-71), and Native Americans (OR=.27, CI=.15-.48) but similar utilization compared with blacks. There were no statistically significant differences in lifetime mental health service utilization for alcohol and drug use disorders among racial and ethnic groups.Conclusions: Asians with lifetime mood disorders underutilized mental health services even after adjustment was made for socioeconomic variables and years of residency in the United States. Future studies of culture-specific attitudes, correlates, and barriers to mental health service utilization are warranted. [ABSTRACT FROM AUTHOR]

RATIONALE: Administration of adjuvant corticosteroids to patients with pandemic influenza A/H1N1 2009 (pH1N1) may reduce inflammation and improve outcomes. OBJECTIVES: To assess the effect of adjuvant corticosteroid treatment on the outcome of critically ill patients with pH1N1 infection. METHODS: All adult patients with confirmed pH1N1 admitted to the intensive care unit of 28 hospitals in South Korea from September 2009 to February 2010 were enrolled. Patients with and without adjuvant corticosteroid treatment were retrospectively compared by two risk stratification models: (1) a retrospective cohort study that used propensity score analysis to adjust for confounding by treatment assignment and (2) a propensity-matched case-control study. MEASUREMENTS AND MAIN RESULTS: A total of 245 patients were enrolled in the cohort study, 107 of whom (44%) received adjuvant steroid treatment. In the cohort study, the 90-day mortality rate of patients given steroids (58%, 62 of 107) was significantly higher than that of those not given steroids (27%, 37 of 138) (P < 0.001). The steroid group was more likely to have superinfection such as secondary bacterial pneumonia or invasive fungal infection, and had more prolonged intensive care unit stays than the no-steroid group. Multivariate analysis indicated that steroid treatment was associated with increased 90-day mortality when independent predictors for 90-day mortality and propensity score were considered (adjusted odds ratio, 2.20; 95% confidence interval, 1.03-4.71). In the case-control study, the 90-day mortality rate in the steroid group was 54% (35 of 65) and 31% (20 of 65) in the no-steroid group (McNemar test, P = 0.004). CONCLUSIONS: Adjuvant corticosteroids were significantly associated with higher mortality in critically ill patients with pH1N1 infection. [ABSTRACT FROM AUTHOR]

Propolis is a sticky, resinous material that honey bees collect from various plants, and mix with wax and other secretions. The aim of this study was to evaluate the antidiabetic effect of propolis through an analysis of the expression and enzyme activity of glucose-6-phosphatase (G6Pase) and to elucidate the mechanism by which propolis inhibits G6Pase gene expression. When HepG2 cells were incubated in high glucose media (25 mm), G6Pase expression was induced. Propolis significantly reduced the expression and enzyme activity of G6Pase; however, the hypoglycemic effect was not abolished by the phosphoinositide 3-kinase inhibitor, LY294002, and by the mitogen-activated protein kinase (MAPK) inhibitor, U0126. Propolis inhibited the activity of GSK3α and β via the inhibition of serine and tyrosine phosphorylation, specifically, Y279 for GSK3α and Y216 for GSK3β. The phosphorylations of Y279 and Y216 occur through autophosphorylation by GSK3α/β and are involved in their own activity. Although propolis showed antioxidant activity, antidiabetic effect of propolis was not influenced by hydrogen peroxide and N-acetylcysteine. These results suggest that propolis inhibits the expression of G6Pase by inhibiting the autophosphorylation of Y279 and Y216 of GSK3α and β, respectively, which are involved in the activation of GSK3. These findings suggest that propolis may be a potential antidiabetic agent for the treatment of insulin-insensitive diabetes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Depression is a frequent neuropsychiatric complication of Alzheimer's Disease. METHODS: This study investigated the safety and effectiveness of escitalopram (LEXAPRO) for depression in AD (dAD) as defined by the NIMH consensus criteria in an 8-week, open-label treatment study. CONCLUSION: Escitalopram was efficacious and safe for the treatment of dAD in this study. Larger, controlled studies are warranted to further assess the efficacy for mood and behavioral disturbances in this medically fragile population. Copyright (c) 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

There is increasing evidence that reactive oxygen species (ROS) play a major role in the development of diabetic complications. Oxidative stress is increased in diabetes and in chronic kidney disease (CKD). High glucose upregulates transforming growth factor-[beta]1 (TGF-[beta]1) and angiotensin II (Ang II) in renal cells and high glucose, TGF-[beta]1, and Ang II all generate and signal through ROS. ROS mediate high glucose-induced activation of protein kinase C and nuclear factor-[kappa]B in renal cells. Intensive glycemic control and inhibition of Ang II delay the onset and progression of diabetic nephropathy, in part, through antioxidant activity. Conventional and catalytic antioxidants were shown to prevent or delay the onset of diabetic nephropathy. Transketolase activators and poly (ADP-ribose) polymerase inhibitors were shown to block major biochemical pathways of hyperglycemic damage. Combination of strategies to prevent overproduction of ROS, to increase the removal of preformed ROS, and to block ROS-induced activation of biochemical pathways leading to cellular damage may prove to the effective in preventing the development and progression of CKD in diabetes. [ABSTRACT FROM AUTHOR]

Histone deacetylase (HDAC) inhibitors are currently being tested as anticancer agents in clinical trials. Chromatin remodeling, such as through histone acetylation, is a fundamental phenomenon in eukaryotic cell biology, bearing implications to numerous physiological and pathological phenomena. Here, we discuss recent data from our own laboratory and those of others demonstrating antifibrotic and renoprotective effect of HDAC inhibitors in diabetic kidneys, and the possible mechanisms including the role of reactive oxygen species. HDAC inhibitors may prove to be a novel class of multitarget agents in the treatment of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Background: While several studies have suggested that bipolar disorder may elevate risk of cardiovascular disease, few studies have examined the relationship between mania or hypomania and cardiovascular disease. The purpose of this study is to examine history of manic and hypomanic episodes as an independent risk factor for cardiovascular disease (CVD) during an 11.5 year follow-up of the Baltimore Epidemiologic Catchment Area Follow-up Study.Methods: All participants were psychiatrically assessed face-to-face based on Diagnostic Interview Schedule in 1981 and 1982 and were categorized as having either history of manic or hypomanic episode (MHE; n=58), major depressive episode only (MDE; n=71) or no mood episode (NME; n=1339). Incident cardiovascular disease (CVD; n=67) was determined by self-report of either myocardial infarction (MI) or congestive heart failure (CHF) in 1993-6.Results: Compared with NME subjects, the odds ratio for incident CVD among MHE subjects was 2.97 (95% confidence interval: 1.40, 6.34) after adjusting for putative risk factors.Conclusions: These data suggest that a history of MHE increase the risk of incident CVD among community residents. Recognition of manic symptoms and addressing related CVD risk factors could have long term preventative implications in the development of cardiovascular disease in the community. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide, and classifying the developmental stages of HCC can help with early prognosis and treatment. This study aimed to investigate diagnostic and prognostic molecular signatures underlying the progression of HCC, including tumor initiation and growth, and to classify its developmental stages based on gene expression levels. We integrated data from two cancer systems, including 78 patients with Edmondson-Steiner (ES) grade and 417 patients with TNM stage cancer. Functional profiling was performed using identified signatures. Using a multinomial logistic regression model (MLR), we classified controls, early-stage HCC, and advanced-stage HCC. The model was validated in three independent cohorts comprising 45 patients (neoplastic stage), 394 patients (ES grade), and 466 patients (TNM stage). Multivariate Cox regression was employed for HCC prognosis prediction. We identified 35 genes with gradual upregulation or downregulation in both ES grade and TNM stage patients during HCC progression. These genes are involved in cell division, chromosome segregation, and mitotic cytokinesis, promoting tumor cell proliferation through the mitotic cell cycle. The MLR model accurately differentiated controls, early-stage HCC, and advanced-stage HCC across multiple cancer systems, which was further validated in various independent cohorts. Survival analysis revealed a subset of five genes from TNM stage (HR: 3.27, p < 0.0001) and three genes from ES grade (HR: 7.56, p < 0.0001) that showed significant association with HCC prognosis. The identified molecular signature not only initiates tumorigenesis but also promotes HCC development. It has the potential to improve clinical diagnosis, prognosis, and therapeutic interventions for HCC. This study enhances our understanding of HCC progression and provides valuable insights for precision medicine approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The excessive consumption of dietary sugar induces changes in gut microbiota, which is associated with obesity and metabolic dysregulation. This study investigated the effects of monosaccharide and fructooligosaccharide (FOS) intake on metabolic function and intestinal environment in germ-free (GF) mice lacking gut microbiota. GF mice were provided with a chow diet and administered a water solution containing 15 % glucose, fructose, or FOS for 4 weeks. Compared with FOS, glucose, and fructose induced increased hepatic lipid accumulation, increased adipocyte size in white adipose tissue, and upregulated hepatic lipogenic gene expression. FOS exhibited notably higher activation of hepatic AMP-activated protein kinase compared with those consuming glucose or fructose. Moreover, the number of goblet cells in the intestinal mucosa increased significantly with FOS consumption. Collectively, these findings indicate that while monosaccharides caused metabolic disorders in GF mice, FOS alleviated these disorders and increased the number of goblet cells in the intestinal mucosa. These results provide evidence for the occurrence of these effects independently of the gut microbiota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: NAD(P)-dependent steroid dehydrogenase-like protein (NSDHL), which is involved in breast tumor growth and metastasis, has been implicated in the maintenance of cancer stem cells. However, its role in regulating breast cancer stem-like cells (BCSCs) remains unclear. We have previously reported the clinical significance of NSDHL in patients with estrogen receptor-positive (ER +) breast cancer. This study aimed to elucidate the molecular mechanisms by which NSDHL regulates the capacity of BCSCs in the ER + human breast cancer cell line, MCF-7., Methods: NSDHL knockdown suppressed tumor spheroid formation in MCF-7 human breast cancer cells grown on ultralow-attachment plates. RNA sequencing revealed that NSDHL knockdown induced widespread transcriptional changes in the MCF-7 spheroids. TGF-β signaling pathway was the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway (fold change ≥ 2, P ≤ 0.05) identified in NSDHL-knockdown MCF-7 spheroids compared with the control. In orthotopic tumor models injected with NSDHL-knockdown MCF-7 spheroids, tumor initiation and growth were strongly suppressed compared with those in the control., Results: BCSC populations with CD44+/CD24- and CD49f+/EpCAM + phenotypes and high ALDH activity were decreased in NSDHL-knockdown MCF-7 spheroids and xenograft tumors relative to controls, along with decreased secretion of TGF-β1 and 3, phosphorylation of Smad2/3, and expression of SOX2. In RNA-sequencing data from The (TCGA) database, a positive correlation between the expression of NSDHL and SOX2 was found in luminal-type breast cancer specimens (n = 998). Our findings revealed that NSDHL plays an important role in maintaining the BCSC population and tumor-initiating capacity of ER-positive MCF-7 spheroids, suggesting that NSDHL is an attractive therapeutic target for eliminating BCSCs, thus preventing breast cancer initiation and progression., Conclusions: Our findings suggest that NSDHL regulates the BCSC/tumor-initiating cell population in MCF-7 spheroids and xenograft tumors., (© 2024. The Author(s).)

Importance: Young patients with breast cancer with estrogen receptor (ER)-positive, ERBB2-negative tumors have a poor prognosis. Understanding factors influencing late recurrence is crucial for improving management and outcomes., Objective: To determine whether age is an independent factor associated with late distant recurrence (DR) in young patients with ER-positive, ERBB2-negative cancers without distant metastasis within 5 years from surgery., Design, Setting, and Participants: This multicenter retrospective cohort study analyzed clinical records of patients with breast cancer who underwent surgery from January 2000 to December 2011 with at least 5 years of follow-up. The study was conducted at Samsung Medical Center, Gangnam Severance Hospital, and Seoul National University Hospital, including patients aged 45 years or younger with ER-positive, ERBB2-negative tumors, no DR within 5 years after surgery, no neoadjuvant chemotherapy, and at least 2 years of endocrine therapy. The data analysis period was from January 4, 2023, to March 21, 2024., Exposure: Age, grouped as 21 to 35 years, 36 to 40 years, and 41 to 45 years., Main Outcomes and Measures: The primary outcome was the incidence of late DR at 5 to 10 years after surgery. Survival outcomes, including late distant metastasis-free survival (DMFS), were evaluated in different age groups., Results: Among 2772 patients included, 370 (13.3%) were aged 21 to 35 years, 885 (31.9%) were aged 36 to 40 years, and 1517 (54.7%) were aged 41 to 45 years. The median (range) follow-up was 10.8 (5.0-21.4) years. The youngest group had a poorer histologic grade (eg, histologic grade 3: 107 patients aged 21-35 years [28.9%]; 149 patients aged 36-40 years [16.8%]; 273 patients aged 41-45 years [18.0%]) and more frequent chemotherapy (307 patients aged 21-35 years [83.0%]; 697 patients aged 36-40 years [78.8%]; 1111 patients aged 41-45 years [73.2%]). The youngest patients had significantly worse rates of locoregional recurrence-free survival (patients aged 21-35 years, 90.1% [95% CI, 86.8%-93.3%]; patients aged 36-40 years, 94.6% [95% CI, 93.0%-96.2%]; patients aged 41-45 years, 97.7% [95% CI, 96.9%-98.5%]), disease-free survival (patients aged 21-35 years, 79.3% [95% CI, 75.0%-83.9%]; patients aged 36-40 years, 88.7% [95% CI, 86.5%-91.0%]; patients aged 41-45 years, 94.4% [95% CI, 93.2%-95.7%]), and late DMFS (patients aged 21-35 years, 89.3% [95% CI, 86.0%-92.9%]; patients aged 36-40 years: 94.2% [95% CI, 92.5%-95.9%]; patients aged 41-45 years: 97.2% [95% CI, 96.3%-98.1%]) but not overall survival (patients aged 21-35 years, 96.9% [95% CI, 95.0%-98.9%]; patients aged 36-40 years, 98.2% [95% CI, 97.2%-99.2%]; patients aged 41-45 years, 98.9% [95% CI, 98.3%-99.5%]). Multivariable analysis showed lower hazard for late DR in the older groups compared with the youngest group (age 36-40 years: hazard ratio, 0.53; 95% CI, 0.34-0.82; P = .001; age 41-45 years: hazard ratio, 0.30; 95% CI, 0.20-0.47; P < .001)., Conclusions and Relevance: In this retrospective cohort study, age was an independent factor associated with late DR in young patients with ER-positive, ERBB2-negative breast cancer. Younger age was associated with worse locoregional recurrence-free survival, disease-free survival, and late DMFS, highlighting the importance of long-term monitoring and potential for personalized treatment approaches based on age, particularly for younger patients with ER-positive, ERBB2-negative breast cancer.

Background: Biological sex influences the risk of depression and cognitive impairment, but its role in relation to postoperative delirium is unclear. This analysis investigates sex differences in delirium risk after coronary artery bypass graft (CABG) surgery and sex-related differences in relation to affective and cognitive symptoms., Methods: This is a secondary analysis of the Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study, a single-site, observational study of a CABG surgery cohort (n = 149). Preoperative characteristics are stratified by sex, and baseline variables that differ by sex are evaluated to understand whether sex modifies their relationships with delirium. We also evaluate sex differences in one-month depression and cognition., Results: Female sex is associated with several delirium risk factors, including higher risk of preoperative depression and middle cerebral artery (MCA) stenosis. MCA stenosis was statistically associated with delirium only among women (OR 15.6, 95% CI 1.5, 164.4); mild cognitive impairment (MCI) was associated with delirium only in men (OR 4.6, 95% CI 1.2, 17.9). Other sex-based differences failed to reach statistical significance. Depression remained commoner among women 1 month post-CABG., Conclusions: Women in this CABG cohort were more likely to have depression at baseline and 1 month postoperatively, as well as MCA stenosis and postoperative delirium. Sex might modify the relationship between post-CABG delirium and its risk factors including MCA stenosis and MCI. Cerebrovascular disease deserves study as a potential explanation linking female sex and a range of poor outcomes among women with coronary heart disease., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There are few studies that have examined clinical and radiological outcomes at 5 years after isolated medial patellofemoral ligament (MPFL) reconstruction. To date, midterm outcomes after isolated double-bundle (DB) MPFL reconstruction are not well known., Hypothesis: Isolated DB MPFL reconstruction using a patellar suture anchor technique would lead to improved functional scores and radiological findings, and these improvements would remain stable over the 5-year postoperative period., Study Design: Case series; Level of evidence, 4., Methods: Isolated MPFL reconstruction was performed in patients with recurrent patellar instability between March 2013 and February 2017. Clinical and functional evaluations were performed via an interview using the Kujala, Lysholm, and Tegner scores preoperatively and at 6, 12, 24, and 60 months postoperatively. Radiographs were taken preoperatively, immediately postoperatively, and at 24 and 60 months after surgery. Radiographic assessments included measuring the modified Insall-Salvati ratio, congruence angle, and lateral patellofemoral angle., Results: A total of 31 patients (31 knees) underwent isolated MPFL reconstruction; 4 patients did not complete 5-year follow-up, and thus, 27 patients (27 knees) were enrolled in the study. The mean age at the time of surgery was 22.0 ± 6.4 years (range, 14-32 years). All clinical and functional scores significantly improved in the first 2 years ( P < .001), with the mean Kujala, Lysholm, and Tegner scores improving from 52.7 to 90.7, 49.6 to 92.7, and 2.9 to 5.1, respectively. There was no significant difference in scores between 2- and 5-year follow-up. All radiographic parameters significantly improved between preoperatively and immediately postoperatively ( P < .001), with mean values for the modified Insall-Salvati ratio, congruence angle, and lateral patellofemoral angle improving from 1.7° to 1.6°, 5.7° to -6.6°, and 3.0° to 5.9°, respectively. No significant differences were observed in radiographic measurements between the postoperative time points. No patients experienced a patellar redislocation or fracture., Conclusion: The prospective analysis of isolated DB MPFL reconstruction at 5-year follow-up showed that clinical and radiological outcomes significantly improved postoperatively and were maintained to 5 years. These midterm results suggest that isolated DB MPFL reconstruction is an effective treatment option for patients with patellar instability., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Ethnopharmacological Relevance: Orostachys japonica (rock pine) has been used as a folk remedy to treat inflammation, hepatitis, and cancer in East Asia., Aim of the Study: The aim of this study was to investigate the effect of rock pine extract (RPE) on high-fat diet-induced obesity in mice and to examine its effects on gut dysbiosis., Materials and Methods: The characteristic compound of RPE, kaempferol-3-O-rutinoside, was quantified using high-performance liquid chromatography. The prebiotic potential of RPE was evaluated by assessing the prebiotic activity score obtained using four prebiotic strains and high-fat (HF)-induced obesity C57BL/6 mice model. Analysis included examining the lipid metabolism and inflammatory proteins and evaluating the changes in gut permeability and metabolites to elucidate the potential signaling pathways involved., Results: In vitro, RPE enhanced the proliferation of beneficial probiotic strains, including Lactiplantibacillus and Bifidobacterium. HF-induced model showed that the administration of 100 mg/kg/day of RPE for 8 weeks significantly (p < 0.05) reduced the body weight, serum lipid levels, and insulin resistance, which were associated with notable changes in lipid metabolism and inflammation-related markers., Conclusions: Our results demonstrate that rock pine consumption could mitigate obesity and metabolic endotoxemia in HF-fed mice through enhancing intestinal environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Sleep-wake and circadian disruption (SCD) is a core feature of delirium. It has been hypothesized that SCD contributes to delirium pathogenesis; therefore, interventions that prevent or reverse SCD represent an array of promising opportunities in relation to delirium. This review explores the relationship between sleep-wake/circadian physiology and delirium pathophysiology with a focus on neurotransmitter systems. Across potential targets aimed at preventing or treating delirium, three broad approaches are considered: 1. Pharmacological mechanisms that contribute to physiological sleep may preserve or restore next-day cognition in patients with or at risk for delirium (e.g., alpha 2 agonists, dopamine 2 antagonists, serotonin 2 A antagonists, dual orexin receptor antagonists, or GHB agonists); 2. Pharmacological mechanisms that promote wakefulness during the day may combat hypoactive delirium (e.g., adenosine 2 A antagonists, dopamine transporter antagonists, orexin agonists, histamine 3 antagonists); and 3. Melatonergic and other circadian interventions could strengthen the phase or amplitude of circadian rhythms and ensure appropriately entrained timing in patients with or at risk for delirium (e.g., as informed by a person's preexisting circadian phase)., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: There is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established., Methods: The main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive., Results: Among 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % vs. 85.2 %, p = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor., Conclusions: This study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: To assess both the short- and longer-term impact of offering medications for opioid use disorder (MOUD, ie, methadone, buprenorphine, or naltrexone) on rates of all-cause emergency department (ED) visits and acute inpatient admissions (IP) over a 30-month period among Medicaid enrollees with opioid use disorder (OUD) residing in rural communities., Methods: A quasi-experimental retrospective analysis of longitudinal Medicaid claims data among continuously enrolled adult patients with OUD residing in 71 predominantly rural counties in the United States between 2018 and 2020. A cohort of patients receiving MOUD treatment was compared against a contemporaneous propensity score-matched comparison group consisting of those who received no MOUD during the period., Findings: The sample included 5370 patients with OUD in each group. At the index period (ie, the month in which any MOUD was used for the first time), buprenorphine was the most commonly used MOUD (82% of the MOUD treatment group). By the eighth month since the index period, MOUD use dropped below 60% among the MOUD treatment group. Over the 30-month post-MOUD period, MOUD treatment was associated with 24% (112 vs 148 per 1000 per month) and 52% (21 vs 44) lower rates of ED visit and IP admission rates, respectively (P < 0.001), relative to the comparison group. Moreover, the reductions persisted well after the 18th month period., Conclusions: Receipt of MOUD was associated with both immediate- and long-term lower rates in acute care utilization rates among adult Medicaid beneficiaries with OUD residing in rural communities despite significant treatment discontinuation., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Lactic acid bacteria (LAB) are probiotic microorganisms widely used for their health benefits in the food industry. However, recent concerns regarding their safety have highlighted the need for comprehensive safety assessments. In this study, we aimed to evaluate the safety of L. bulgaricus IDCC 3601, isolated from homemade plain yogurt, via genomic, phenotypic, and toxicity-based analyses. L. bulgaricus IDCC 3601 possessed a single circular chromosome of 1,865,001 bp, with a GC content of 49.72%, and 1910 predicted coding sequences. No virulence or antibiotic resistance genes were detected. Although L. bulgaricus IDCC 3601 exhibited antibiotic resistance to gentamicin and kanamycin, this resistance is an intrinsic feature of this species. L. bulgaricus IDCC 3601 did not produce biogenic amines and did not exhibit hemolytic activity. Phenotypic analysis of enzyme activity and carbohydrate fermentation profiles revealed the metabolic features of L. bulgaricus IDCC 3601. Moreover, no deaths or abnormalities were observed in single-dose oral toxicity tests, suggesting that L. bulgaricus IDCC 3601 has no adverse effect on human health. Finally, L. bulgaricus IDCC 3601 inhibited the growth of potential carbapenem-resistant Enterobacteriaceae . Therefore, our results suggest that L. bulgaricus IDCC 3601 is a safe probiotic strain for human consumption.

Background: The incidence of breast cancer among young Asian women is increasing, yet they remain underrepresented in global data. We analyzed the epidemiology and outcomes of Asian patients with breast cancer <40 years old across different subtypes to identify their clinical unmet needs., Patients and Methods: Female patients aged ≥20 years diagnosed with early breast cancer were analyzed from the prospective cohort of the Asian Breast Cancer Cooperative Group (ABCCG). For comparison, data from the Surveillance, Epidemiology, and End Results Program (SEER) cancer registry were used. Patients were categorized into three age groups: young (<40 years), alleged premenopausal mid-age (40-49 years), and alleged postmenopausal (aged ≥50 years). Multivariable Cox proportional hazards models for survival were adjusted for subtypes, histologic grade, T stage, nodal status, and study centers., Results: A total of 45 021 patients with breast cancer from Asian study centers, 496 332 SEER-White patients, and 18 279 SEER-Asian patients were included in the analysis. The median age at diagnosis was younger in the Asian cohort (51 years) compared with SEER-Whites (62 years) and SEER-Asians (58 years; P < 0.0001). In the young-age group, hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer was more prevalent among Asians and SEER-Asians compared with SEER-Whites (61.2% and 59.8% versus 54.7%). In the Asian population, young patients with HR+/HER2- breast cancer exhibited significantly inferior overall survival than the mid-age group (6-year overall survival 94.4% versus 96.6%; mid-age to young-age group hazard ratio 0.62; P < 0.001). Similarly, young patients in SEER-Whites showed an earlier decline in survival compared with the mid-age group (89.1% versus 94.0%; P < 0.001)., Conclusion: ABCCG-Asian patients with breast cancer <40 years old with HR+/HER2- subtypes were more likely to have worse survival outcomes than their mid-age counterparts. Our study highlights the poorer prognosis of young patients and underscores the need for a tailored therapeutic approach, such as ovarian function suppression, particularly considering ethnic factors., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)