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Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 µg/mL, respectively.
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Abies , Espécies em Perigo de Extinção , Endófitos , Policetídeos , Endófitos/química , Policetídeos/farmacologia , Policetídeos/isolamento & purificação , Policetídeos/química , Estrutura Molecular , China , Abies/química , Phomopsis/química , Testes de Sensibilidade Microbiana , Penicillium/química , Bactérias/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , 4-Butirolactona/análogos & derivados , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , 4-Butirolactona/químicaRESUMO
PURPOSES: Our aim is to build and evaluate models to screen for clinically significant nephrolithiasis in overweight and obesity populations using machine learning (ML) methodologies and simple health checkup clinical and urine parameters easily obtained in clinics. METHODS: We developed ML models to screen for clinically significant nephrolithiasis (kidney stone > 2 mm) in overweight and obese populations (body mass index, BMI ≥ 25 kg/m2) using gender, age, BMI, gout, diabetes mellitus, estimated glomerular filtration rate, bacteriuria, urine pH, urine red blood cell counts, and urine specific gravity. The data were collected from hospitals in Kaohsiung, Taiwan between 2012 and 2021. RESULTS: Of the 2928 subjects we enrolled, 1148 (39.21%) had clinically significant nephrolithiasis and 1780 (60.79%) did not. The testing dataset consisted of data collected from 574 subjects, 235 (40.94%) with clinically significant nephrolithiasis and 339 (59.06%) without. One model had a testing area under curve of 0.965 (95% CI, 0.9506-0.9794), a sensitivity of 0.860 (95% CI, 0.8152-0.9040), a specificity of 0.947 (95% CI, 0.9230-0.9708), a positive predictive value of 0.918 (95% CI, 0.8820-0.9544), and negative predictive value of 0.907 (95% CI, 0.8756-0.9371). CONCLUSION: This ML-based model was found able to effectively distinguish the overweight and obese subjects with clinically significant nephrolithiasis from those without. We believe that such a model can serve as an easily accessible and reliable screening tool for nephrolithiasis in overweight and obesity populations and make possible early intervention such as lifestyle modifications and medication for prevention stone complications.
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Diabetes Mellitus , Cálculos Renais , Nefrolitíase , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Nefrolitíase/diagnóstico , Nefrolitíase/epidemiologia , Nefrolitíase/etiologia , Obesidade/complicações , Obesidade/epidemiologia , Cálculos Renais/complicações , Índice de Massa CorporalRESUMO
With the increasing prevalence of Staphylococcus aureus infections, rapid emergence of drug resistance and the slow healing of infected wounds, developing an efficient antibiotic-free multifunctional wound dressing for inhibiting S. aureus and simultaneously facilitating wound healing have become a huge challenge. Due to their excellent biocompatibility and biodegradability, some carbopol hydrogels based on plant extracts or purified compounds have already been applied in wound healing treatment. In China, Euphorbia humifusa Willd. (EuH) has been traditionally used as a medicine and food homologous medicine for the treatment of furuncles and carbuncles mainly caused by S. aureus infection. In an earlier study, EuH-originated flavonoids quercetin (QU) and luteolin (LU) could serve as a potential source for anti-S. aureus drug discovery when used in synergy. However, the in vivo effects of QU and LU on S. aureus-infected wound healing are still unknown. In this study, we found a series of Carbopol 940-based hydrogels loading QU and LU in combination could disinfect S. aureus and also could promote wound healing. In the full-thickness skin defect mouse model infected with S. aureus, the wound contraction ratio, bacterial burden, skin hyperplasia and inflammation score, as well as collagen deposition and blood vessels were then investigated. The results indicate that the optimized QL2 [QU (32 µg mL-1)-LU (8 µg mL-1)] hydrogel with biocompatibility significantly promoted S. aureus-infected wound healing through anti-infection, anti-inflammation, collagen deposition, and angiogenesis, revealing it as a promising alternative for infected wound repair.
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An investigation on the secondary metabolites from a rice culture broth of the endophytic fungus Neurospora terricola HDF-Br-2 derived from the vulnerable conifer Pseudotsuga gaussenii led to the isolation and characterization of 34 structurally diverse polyketides (1-34). Seven of them are previously undescribed, including five unprecedented dihydropyran-containing (terricoxanthones A-E, 1-5, resp.) and one rare tetrahydrofuran-containing (terricoxanthone F, 6) dimeric xanthones. The structures were elucidated by spectroscopic methods and single-crystal X-ray diffraction analyses. Terricoxanthones each were obtained as a racemic mixture. Their plausible biosynthetic relationships were briefly proposed. Compounds 6, aspergillusone A (8), and alatinone (27) displayed considerable inhibition against Candida albicans with MIC values of 8-16 µg/mL. 4-Hydroxyvertixanthone (12) and 27 exhibited significant inhibitory activities against Staphylococcus aureus, with MIC values of 4-8 µg/mL. Furthermore, compounds 8 and 27 could disrupt biofilm of S. aureus and C. albicans at 128 µg/mL. The findings not only extend the skeletons of xanthone dimers and contribute to the diversity of metabolites of endophytes associated with the endangered Chinese conifer P. gaussenii, but could further reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics.
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Neurospora , Pseudotsuga , Traqueófitas , Xantonas , Staphylococcus aureus , Fungos , Xantonas/química , Estrutura Molecular , Testes de Sensibilidade MicrobianaRESUMO
Human brain microvascular endothelial cells (hBMECs) are the main component cells of the blood-brain barrier (BBB) and play a crucial role in responding to viral infections to prevent the central nervous system (CNS) from viral invasion. Interferon-inducible transmembrane protein 1 (IFITM1) is a multifunctional membrane protein downstream of type-I interferon. In this study, we discovered that hIFITM1 expression was highly upregulated in hBMECs during Japanese encephalitis virus (JEV) infection. Depletion of hIFITM1 with CRISPR/Cas9 in hBMECs enhanced JEV replication, while overexpression of hIFITM1 restricted the viruses. Additionally, overexpression of hIFITM1 promoted the monolayer formation of hBMECs with a better integrity and a higher transendothelial electrical resistance (TEER), and reduced the penetration of JEV across the BBB. However, the function of hIFITM1 is governed by palmitoylation. Mutations of palmitoylation residues in conserved CD225 domain of hIFITM1 impaired its antiviral capacity. Moreover, mutants retained hIFITM1 in the cytoplasm and lessened its interaction with tight junction protein Occludin. Taken together, palmitoylation of hIFITM1 is essential for its antiviral activity in hBMECs, and more notably, for the maintenance of BBB homeostasis.
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Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Humanos , Barreira Hematoencefálica/metabolismo , Vírus da Encefalite Japonesa (Espécie)/genética , Células Endoteliais/metabolismo , Lipoilação , Encefalite Japonesa/genética , Antivirais/metabolismo , Interferons/metabolismoRESUMO
Objective: To overcome limitations of open surgery artificial intelligence (AI) models by curating the largest collection of annotated videos and to leverage this AI-ready data set to develop a generalizable multitask AI model capable of real-time understanding of clinically significant surgical behaviors in prospectively collected real-world surgical videos. Design, Setting, and Participants: The study team programmatically queried open surgery procedures on YouTube and manually annotated selected videos to create the AI-ready data set used to train a multitask AI model for 2 proof-of-concept studies, one generating surgical signatures that define the patterns of a given procedure and the other identifying kinematics of hand motion that correlate with surgeon skill level and experience. The Annotated Videos of Open Surgery (AVOS) data set includes 1997 videos from 23 open-surgical procedure types uploaded to YouTube from 50 countries over the last 15 years. Prospectively recorded surgical videos were collected from a single tertiary care academic medical center. Deidentified videos were recorded of surgeons performing open surgical procedures and analyzed for correlation with surgical training. Exposures: The multitask AI model was trained on the AI-ready video data set and then retrospectively applied to the prospectively collected video data set. Main Outcomes and Measures: Analysis of open surgical videos in near real-time, performance on AI-ready and prospectively collected videos, and quantification of surgeon skill. Results: Using the AI-ready data set, the study team developed a multitask AI model capable of real-time understanding of surgical behaviors-the building blocks of procedural flow and surgeon skill-across space and time. Through principal component analysis, a single compound skill feature was identified, composed of a linear combination of kinematic hand attributes. This feature was a significant discriminator between experienced surgeons and surgical trainees across 101 prospectively collected surgical videos of 14 operators. For each unit increase in the compound feature value, the odds of the operator being an experienced surgeon were 3.6 times higher (95% CI, 1.67-7.62; P = .001). Conclusions and Relevance: In this observational study, the AVOS-trained model was applied to analyze prospectively collected open surgical videos and identify kinematic descriptors of surgical skill related to efficiency of hand motion. The ability to provide AI-deduced insights into surgical structure and skill is valuable in optimizing surgical skill acquisition and ultimately improving surgical care.
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Inteligência Artificial , Aprendizado de Máquina , Humanos , Estudos Retrospectivos , Gravação em Vídeo/métodos , Centros Médicos AcadêmicosRESUMO
This cross-sectional study assesses the level of adoption of 5 new tools that promote high quality and transparency in surgical research.
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Publicações Periódicas como Assunto , Humanos , Editoração , Revisão da Pesquisa por ParesRESUMO
Primary care providers (PCPs) are considered the first-line defenders in preventive care. Patients seeking service from the same PCP constitute that physician's panel, which determines the overall supply and demand of the physician. The process of allocating patients to physician panels is called panel design. This study quantifies patient overflow and builds a mathematical model to evaluate the effect of two implementable panel assignments. In specialized panel assignment, patients are assigned based on their medical needs or visit frequency. In equal panel assignment, patients are distributed uniformly to maintain a similar composition across panels. We utilize majorization theory and numerical examples to evaluate the performance of the two designs. The results show that specialized panel assignment outperforms when (1) patient demands and physician capacity are relatively balanced or (2) patients who require frequent visits incur a higher shortage penalty. In a simulation model with actual patient arrival patterns, we also illustrate the robustness of the results and demonstrate the effect of switching panel policy when the patient pool changes over time.
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Médicos , Humanos , Modelos Teóricos , Simulação por Computador , Instituições de Assistência Ambulatorial , Fatores de TempoRESUMO
BACKGROUND: Japanese encephalitis virus (JEV) remains a predominant cause of Japanese encephalitis (JE) globally. Its infection is usually accompanied by disrupted bloodâbrain barrier (BBB) integrity and central nervous system (CNS) inflammation in a poorly understood pathogenesis. Productive JEV infection in brain microvascular endothelial cells (BMECs) is considered the initial event of the virus in penetrating the BBB. Type I/III IFN and related factors have been described as negative regulators in CNS inflammation, whereas their role in JE remains ambiguous. METHODS: RNA-sequencing profiling (RNA-seq), real-time quantitative PCR, enzyme-linked immunosorbent assay, and Western blotting analysis were performed to analyze the gene and protein expression changes between mock- and JEV-infected hBMECs. Bioinformatic tools were used to cluster altered signaling pathway members during JEV infection. The shRNA-mediated immune factor-knockdown hBMECs and the in vitro transwell BBB model were utilized to explore the interrelation between immune factors, as well as between immune factors and BBB endothelial integrity. RESULTS: RNA-Seq data of JEV-infected hBMECs identified 417, 1256, and 2748 differentially expressed genes (DEGs) at 12, 36, and 72 h post-infection (hpi), respectively. The altered genes clustered into distinct pathways in gene ontology (GO) terms and KEGG pathway enrichment analysis, including host antiviral immune defense and endothelial cell leakage. Further investigation revealed that pattern-recognition receptors (PRRs, including TLR3, RIG-I, and MDA5) sensed JEV and initiated IRF/IFN signaling. IFNs triggered the expression of interferon-induced proteins with tetratricopeptide repeats (IFITs) via the JAK/STAT pathway. Distinct PRRs exert different functions in barrier homeostasis, while treatment with IFN (IFN-ß and IFN-λ1) in hBMECs stabilizes the endothelial barrier by alleviating exogenous destruction. Despite the complex interrelationship, IFITs are considered nonessential in the IFN-mediated maintenance of hBMEC barrier integrity. CONCLUSIONS: This research provided the first comprehensive description of the molecular mechanisms of hostâpathogen interplay in hBMECs responding to JEV invasion, in which type I/III IFN and related factors strongly correlated with regulating the hBMEC barrier and restricting JEV infection. This might help with developing an attractive therapeutic strategy in JE.
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Vírus da Encefalite Japonesa (Espécie) , Vírus da Encefalite Japonesa (Subgrupo) , Encefalite Japonesa , Interferon Tipo I , Humanos , Encefalite Japonesa/genética , Barreira Hematoencefálica , Interferon lambda , Células Endoteliais , Janus Quinases , Fatores de Transcrição STAT , Transdução de Sinais , InflamaçãoRESUMO
PURPOSE: To investigate the prevalence of bladder neck incompetence (BNI) and the anatomic differences between different types of urinary incontinence (UI) and overactive bladder (OAB) by transrectal sonography, and to investigate these differences among those with stress UI (SUI) or mixed UI (MUI) who exhibited de novo or persistent OAB symptoms following anti-incontinence surgery. METHODS: A retrospective analysis was conducted on a total of 184 patients with SUI, MUI, urge UI (UUI), or OAB dry who underwent transrectal ultrasound between 2017 and 2022. The presence of BNI and urethral incompetence assessed by transrectal ultrasound were recorded in all included patients, and recorded preoperatively and postoperatively among patients with SUI and MUI who underwent anti-incontinence surgery. RESULTS: Among the patients, 91%, 84%, 76%, and 71% exhibited BNI in MUI, SUI, UUI, OAB dry group, respectively. Significantly higher rate of patients with BNI were found in MUI than in OAB dry group. Patients with OAB symptoms after anti-incontinence surgery exhibited significantly higher rates of BNI and urethral incompetence than those who did not have postoperative OAB symptoms. Among MUI patients with preoperative BNI, significantly lower rate of postoperative BNI and urethral incompetence was observed in individuals who had improved OAB symptoms after surgery, compared to those without improvement. CONCLUSION: A higher BNI rate was observed in the MUI group. A significantly higher BNI rate was observed in women with OAB symptoms after anti-incontinence surgery. Patients with MUI had improved OAB symptoms if BNI was successfully corrected after anti-incontinence surgery.
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Bexiga Urinária Hiperativa , Incontinência Urinária por Estresse , Incontinência Urinária , Humanos , Feminino , Bexiga Urinária Hiperativa/epidemiologia , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/diagnóstico , Incontinência Urinária por Estresse/epidemiologia , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/cirurgia , Estudos Retrospectivos , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/cirurgia , Incontinência Urinária de Urgência/diagnósticoRESUMO
Open science practices are research tools used to improve research quality and transparency. These practices have been used by researchers in various medical fields, though the usage of these practices in the surgical research ecosystem has not been quantified. In this work, we studied the use of open science practices in general surgery journals. Eight of the highest-ranked general surgery journals by SJR2 were chosen and their author guidelines were reviewed. From each journal, 30 articles published between January 1, 2019 and August 11, 2021 were randomly chosen and analyzed. Five open science practices were measured (preprint publication prior to peer-reviewed publication, use of Equator guidelines, study protocol preregistration prior to peer-reviewed publication, published peer review, and public accessibility of data, methods, and/or code). Across all 240 articles, 82 (34%) used one or more open science practices. Articles in the International Journal of Surgery showed greatest use of open science practices, with a mean of 1.6 open science practices compared to 0.36 across the other journals (p<.001). Adoption of open science practices in surgical research remains low, and further work is needed to increase utilization of these tools.
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Four undescribed palmarumycin-type spirodioxynaphthalenes (phyligustricins A-D) and a known biogenetic precursor (palmarumycin BG1) were isolated from a solid fermentation of Phyllosticta ligustricola HDF-L-2, an endophyte associated with the endangered Chinese conifer Pseudotsuga gaussenii. The structures were elucidated by spectroscopic methods, single-crystal X-ray diffraction analyses, and electronic circular dichroism calculations. Both phyligustricins A and B have an unprecedented spirodioxynaphthalene-derived skeleton containing an extra 4H-furo [3,2-c]pyran-4-one moiety, while phyligustricins C and D are p-hydroxy-phenethyl substituted spirodioxynaphthalenes. The plausible biosynthetic relationships of the isolates were briefly proposed. Phyligustricins C and D and palmarumycin BG1 showed considerable antibacterial activity against Staphylococcus aureus, each with an MIC value of 16 µg/mL. Palmarumycin BG1 displayed significant inhibitory effects against ACL and ACC1, with IC50 values of 1.60 and 8.00 µM, respectively.
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Ascomicetos , Pseudotsuga , Ascomicetos/química , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
PURPOSE: Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. METHODS: The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. RESULTS: Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). CONCLUSION: Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.
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Bexiga Urinária Hiperativa , Humanos , Estudos Prospectivos , Micção/fisiologia , Antagonistas Muscarínicos/uso terapêutico , Biomarcadores , UrodinâmicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia humifusa Willd., known as Di-Jin-Cao in Chinese, has long been utilized as a traditional herb for the treatment of furuncles and carbuncles mainly caused by Staphylococcus aureus infection. Despite extensive chemical and pharmacological studies reported previously for E. humifusa, the antibacterial and antibiofilm activities against S. aureus as well as the related mechanism of action (MoA) remain largely obscure. AIM OF THE STUDY: To investigate the antibacterial and antibiofilm activities of the preferred fractions and compounds from E. humifusa against S. aureus and assess the associated MoA. MATERIALS AND METHODS: The bioactive fractions and compounds were obtained from the 75% ethanol extract of E. humifusa (75%-EEEH) with the assistance of the related antibacterial and antibiofilm screening. Their antibacterial activities were determined using the broth microdilution method, whilst the inhibition of biofilm formation and the disruption of preformed biofilm were assessed by crystal violet staining and confocal laser scanning microscopy (CLSM). To achieve more effective therapies, the combinatory effects of different components were also studied. The biofilm metabolic activities of isolated compounds were evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. The scanning electron microscopy (SEM) and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to explore the antibiofilm mechanism. RESULTS: Fractions DJC06 and DJC07 collected from the ethyl acetate extract of the 75%-EEEH exhibited antibacterial activity (MIC = 256 µg/mL) against S. aureus and further separation of these two fractions led to the isolation and characterization of 22 compounds. Among the isolates, luteolin (LU), quercetin (QU), and kaempferol (KA) are the verified components associated with the antibacterial and antibiofilm activities by displaying individual or combinational MIC values of 8-128 µg/mL and 70.9-99.7% inhibition for biofilm formation. Importantly, QU and KA can work in synergy with LU to significantly enhance the efficacy via destroying cell integrity, increasing membrane permeability, and down-regulating the biofilm-related gene expression. CONCLUSIONS: The preferred fractions and compounds from E. humifusa exerted desired antibacterial and antibiofilm efficacy against S. aureus via a MoA involving cell morphology disruption and altered genes expression. The findings herein not only support its traditional use in the treatment of furuncles and carbuncles, but reveal E. humifusa is a potential source for producing promising antibiofilm alternatives against S. aureus and highlight the isolated components (LU, QU, KA) that can potentiate the efficacy when used in synergy.
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Carbúnculo , Euphorbia , Furunculose , Infecções Estafilocócicas , Animais , Staphylococcus aureus , Antibacterianos/farmacologia , Infecções Estafilocócicas/microbiologia , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
This cross-sectional study uses the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis reporting guideline to assess 120 published studies about surgical prediction models.
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Modelos Estatísticos , Humanos , PrognósticoRESUMO
BACKGROUND: Despite meeting operative indications for primary hyperparathyroidism (PHPT), many patients never undergo parathyroidectomy. We hypothesized that patients with limited English proficiency (LEP) would be less likely to undergo parathyroidectomy than English-proficient (EP) patients. STUDY DESIGN: We retrospectively analyzed patients with PHPT from an institution-wide registry who met operative criteria between 2010 and 2018. The cohort was stratified by English proficiency. Univariate associations between sociodemographic and clinical factors with parathyroidectomy were assessed. A multivariable logistic regression model was created to assess independent predictors of parathyroidectomy. RESULTS: Among a cohort of 1,104 patients, 262 (24%) underwent parathyroidectomy. LEP patients (n = 135, 12%) were significantly younger (mean age 62 vs. 69, p < 0.001), more likely non-white race and ethnicity (p < 0.001), and less likely to have private insurance (p < 0.001). After adjusting for covariates, non-English and non-Spanish preferred language was an independent negative predictor of undergoing parathyroidectomy (OR 0.46, 95% CI 0.21-0.95, p = 0.037). CONCLUSIONS: Limited English proficiency may be an independent barrier to appropriate surgical management of PHPT. Systems-level and disease-specific interventions are needed to address this disparity faced by patients with LEP.
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Hiperparatireoidismo Primário , Proficiência Limitada em Inglês , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Paratireoidectomia , Etnicidade , Hiperparatireoidismo Primário/cirurgiaRESUMO
BACKGROUND: A majority of patients with primary hyperparathyroidism are not referred for surgical evaluation. We hypothesized that disparities in the rate of surgeon evaluation by language, race and ethnicity, and insurance contribute to this deficit. METHODS: We queried our institutional electronic health record registry for patients with first-incident hypercalcemia between 2010 and 2018 and subsequent biochemical diagnosis of primary hyperparathyroidism. We used the Kaplan-Meier method and Cox proportional hazards modeling to investigate estimated time to surgeon evaluation by language, race and ethnicity, and insurance status. RESULTS: Of 1,333 patients with a diagnosis of primary hyperparathyroidism, 74% were female, 67% were White, 44% were privately insured, and 88% preferred English. Fewer than one third (n = 377; 28%) were evaluated by a surgeon. After adjusting for demographic and clinical factors, Asian (hazard ratio = 0.38; 95% confidence interval, 0.18-0.84; P = .016) and Black or African American patients (hazard ratio = 0.59; 95% confidence interval, 0.39-0.90; P = .014) had a lower rate of surgeon evaluation compared to White patients. Although patients with Medicaid had a lower rate of surgeon evaluation compared to privately insured patients (hazard ratio = 0.52; 95% confidence interval, 0.35-0.77; P = .001), there was no difference in rate for those with Medicare or who were uninsured. Patients with non-English and non-Spanish language had a lower rate of evaluation compared to those who preferred English (hazard ratio = 0.47; 95% confidence interval, 0.23-0.98; P = .043). CONCLUSION: Rates of surgeon evaluation vary by race and ethnicity, insurance status, and preferred language. Evaluation of factors contributing to these disparities is needed to improve access to surgeon referral.
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Hiperparatireoidismo Primário , Medicare , Idoso , Humanos , Estados Unidos , Feminino , Masculino , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/cirurgia , Cobertura do Seguro , Pessoas sem Cobertura de Seguro de Saúde , Medicaid , Disparidades em Assistência à SaúdeRESUMO
The establishment of Japanese encephalitis virus (JEV) infection in brain microvascular endothelial cells (BMECs) is thought to be a critical step to induce viral encephalitis with compromised blood-brain barrier (BBB), and the mechanisms involved in this process are not completely understood. In this study, we found that epidermal growth factor receptor (EGFR) is related to JEV escape from interferon-related host innate immunity based on a STRING analysis of JEV-infected primary human brain microvascular endothelial cells (hBMECs) and mouse brain. At the early phase of the infection processes, JEV induced the phosphorylation of EGFR. In JEV-infected hBMECs, a rapid internalization of EGFR that co-localizes with the endosomal marker EEA1 occurred. Using specific inhibitors to block EGFR, reduced production of viral particles was observed. Similar results were also found in an EGFR-KO hBMEC cell line. Even though the process of viral infection in attachment and entry was not noticeably influenced, the induction of IFNs in EGFR-KO hBMECs was significantly increased, which may account for the decreased viral production. Further investigation demonstrated that EGFR downstream cascade ERK, but not STAT3, was involved in the antiviral effect of IFNs, and a lowered viral yield was observed by utilizing the specific inhibitor of ERK. Taken together, the results revealed that JEV induces EGFR activation, leading to a suppression of interferon signaling and promotion of viral replication, which could provide a potential target for future therapies for the JEV infection.
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BACKGROUND: Four-dimensional (4D) CT localization allows minimally invasive parathyroidectomy as treatment for primary hyperparathyroidism (PHPT), but false positive localization is frequent. We sought to characterize the ability of 4D CT to predict four-gland hyperplasia (HP) based on the size of candidate lesions. STUDY DESIGN: We retrospectively analyzed patients with PHPT who underwent 4D CT imaging and parathyroidectomy between 2014 and 2020 from a prospectively collected institutional database. The cohort was stratified into two groups, HP vs single adenoma (SA) and double adenoma (DA), based on operative findings and pathology. Logistic regression models assessed the association between the greatest diameter of the dominant candidate lesion on 4D CT and the outcomes of four-gland hyperplasia vs SA and DA. RESULTS: Among a cohort of 240 patients, 41 were found to have HP, and 199 had adenomas (SA = 155, DA = 44). Patients with HP were less likely to have a preoperative calcium level greater than 1 mg/dL above the upper limit of normal compared with patients with adenomas (63% vs 81%, p = 0.02) and more likely to report symptoms (61% vs 43%, p = 0.04). After adjusting for BMI, we found an estimated 13% reduction in odds of HP for every 1-mm increase in the greatest diameter of dominant candidate lesions identified on 4D CT scan (odds ratio 0.87, 95% CI 0.78 to 0.96, p = 0.009). CONCLUSIONS: A smaller size of the dominant lesion on 4D CT scan is associated with an increased risk of HP in PHPT. Use of 4D CT imaging localization may provide evidence for differentiating HP from adenomas.
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Adenoma , Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Adenoma/complicações , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Tomografia Computadorizada Quadridimensional/métodos , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/cirurgia , Hiperplasia/complicações , Hiperplasia/diagnóstico por imagem , Hiperplasia/cirurgia , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Estudos RetrospectivosRESUMO
There is a great need for a diagnostic tool using simple clinical information collected from patients to diagnose uric acid (UA) stones in nephrolithiasis. We built a predictive model making use of machine learning (ML) methodologies entering simple parameters easily obtained at the initial clinical visit. Socio-demographic, health, and clinical data from two cohorts (A and B), both diagnosed with nephrolithiasis, one between 2012 and 2016 and the other between June and December 2020, were collected before nephrolithiasis treatment. A ML-based model for predicting UA stones in nephrolithiasis was developed using eight simple parameters-sex, age, gout, diabetes mellitus, body mass index, estimated glomerular filtration rate, bacteriuria, and urine pH. Data from Cohort A were used for model training and validation (ratio 3:2), while data from Cohort B were used only for validation. One hundred and forty-six (13.3%) out of 1098 patients in Cohort A and 3 (4.23%) out of 71 patients in Cohort B had pure UA stones. For Cohort A, our model achieved a validation AUC (area under ROC curve) of 0.842, with 0.8475 sensitivity and 0.748 specificity. For Cohort B, our model achieved 0.936 AUC, with 1.0 sensitivity, and 0.912 specificity. This ML-based model provides a convenient and reliable method for diagnosing urolithiasis. Using only eight readily available clinical parameters, including information about metabolic disorder and obesity, it distinguished pure uric acid stones from other stones before treatment.