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A novel approach was developed to simultaneously determine the contents of vitamins D2, D3, K1, and K2 in yogurt fortified with nanoencapsulated vitamins D and K. This method combines QuEChERS extraction with UPLC-APCI-MS/MS analysis. Optimization of the QuEChERS process included fine-tuning the addition of salts using response surface methodology based on the Box-Behnken design. Under the optimized conditions, the developed method exhibited an excellent linearity (R2 > 0.999) across concentrations ranging from 0.5 to 500 µg/L. The limits of detection and quantification (LOD and LOQ) were found to be 0.01-0.04 µg/L and 0.04-0.11 µg/L, respectively, with precision, accuracy, and recovery rates exceeding 94.88 %, and accompanied by acceptable relative standard deviations. Comparative analysis with traditional methodologies revealed the significant advantages of the proposed approach. Previous techniques such as liquid-liquid extraction combined with saponification are time-consuming and require high sample quantities. In addition, dispersive liquid-liquid microextraction requires a long analysis time and exhibits a poor sensitivity, particularly in terms of its LOD and LOQ values. In contrast, our method offers a straightforward, efficient, and reliable sample preparation technique suitable for detecting vitamins D2, D3, K1, and K2 in a yogurt matrix. This study not only demonstrates the feasibility of applying the QuEChERS method for stable vitamin quantification in yogurt, but it also represents an innovative contribution to enhancing the detection sensitivity and efficiency in food analysis. By emphasizing these methodological advancements and comparative benefits, this research underscores the significance of adopting advanced analytical approaches in food science.
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Avian pathogenic Escherichia coli (APEC) causes enormous economic losses and is a primary contributor to the emergence of multidrug resistance (MDR)-related problems in the poultry industry. Bacteriophage (phage) therapy has been successful in controlling MDR, but phage-resistant variants have rapidly emerged through the horizontal transmission of diverse phage defense systems carried on mobile genetic elements. Consequently, while multiple phage cocktails are recommended for phage therapy, there is a growing need to explore simpler and more cost-effective phage treatment alternatives. In this study, we characterized two novel O78-specific APEC phages, φWAO78-1 and φHAO78-1, in terms of their morphology, genome, physicochemical stability and growth kinetics. Additionally, we assessed the susceptibility of thirty-two O78 APEC strains to these phages. We analyzed the roles of highly susceptible cells in intestinal settlement and fecal shedding (susceptible cell-assisted intestinal settlement and shedding, SAIS) of phages in chickens via coinoculation with phages. Furthermore, we evaluated a new strategy, susceptible cell-assisted resistant cell killing (SARK), by comparing phage susceptibility between resistant cells alone and a mixture of resistant and highly susceptible cells in vitro. As expected, high proportions of O78 APEC strains had already acquired multiple phage defense systems, exhibiting considerable resistance to φWAO78-1 and φHAO78-1. Coinoculation of highly susceptible cells with phages prolonged phage shedding in feces, and the coexistence of susceptible cells markedly increased the phage susceptibility of resistant cells. Therefore, the SAIS and SARK strategies were demonstrated to be promising both in vivo and in vitro.
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Bacteriófagos , Infecções por Escherichia coli , Doenças das Aves Domésticas , Animais , Bacteriófagos/genética , Galinhas , Escherichia coli/genética , Colífagos , Morte Celular , Doenças das Aves Domésticas/terapiaRESUMO
Respiratory syncytial virus (RSV) constitutes a significant cause of respiratory illness and mortality among older adults, a demographic that is expanding with considerable impact on healthcare systems worldwide. The actual burden of RSV in this population may still be underestimated, owing to factors such as low awareness and suboptimal diagnostic sensitivity in adults, the lack of robust RSV surveillance systems, and the infrequent use of diagnostic testing. Recent advancements in respiratory virus detection have spurred further exploration into appropriate preventive and therapeutic strategies. The recent approval of two vaccines highlights the critical need for the precise estimation of the RSV disease burden to optimize the effectiveness and cost-efficiency of immunization programs. This narrative review aimed to summarize the existing knowledge of the RSV burden in adults with a particular focus on older adults, incorporating data from Korea. Overall, current estimates indicate that the annual RSV attack rate in the general adult population ranges from 1 - 7%, increasing to approximately 4 - 10% among elderly and high-risk groups. The in-hospital mortality rate can be estimated to be around 7 - 10%, rising up to 40% among intensive care unit-admitted patients. To elucidate RSV's disease burden, further continuing research, including population-based studies, is necessary.
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PURPOSE: To assess long-term clinical results following bilateral Tecnis Symfony ZXR00 intraocular lens implantation with mini-monovision. METHODS: The medical records of cataract patients who underwent bilateral implantation of ZXR00 with intended mini-monovision (target refraction of -0.3 diopters [D] in dominant eye and -0.6 D in nondominant eye) between April 2019 and March 2021 were assessed. Postoperative uncorrected distance visual acuity (UDVA), corrected distance VA (CDVA), uncorrected intermediate VA (UIVA), uncorrected near VA (UNVA), and rate of spectacle dependence for near distance were investigated at 3 months and 2 years after surgery. RESULTS: This study included 61 patients (122 eyes) with average age of 61.8 ± 7.7 years. At 2 years postoperatively, binocular logarithm of the minimum angle of resolution UDVA, UIVA, UNVA, and CDVA were 0.086 ± 0.094, 0.056 ± 0.041, 0.140 ± 0.045, and 0.012 ± 0.024, respectively. The monocular manifest refraction spherical equivalent was -0.31 ± 0.38 in the dominant eye and -0.53 ± 0.47 in the nondominant eye at 3 months postoperatively, and -0.38 ± 0.43 in the dominant eye and -0.61 ± 0.54 in the nondominant eye at 2 years postoperatively. Eight out of 61 patients (13.1%) needed glasses 3 months after surgery, and nine out of 61 patients (14.8%) needed glasses 2 years after surgery. CONCLUSIONS: The bilateral implantation of ZXR00s with mini-monovision allows for a good VA at wide range of distance from far to near, thereby resulting in high rate of spectacle independence. These results have held up well even after 2 years after surgery.
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Lentes Intraoculares , Facoemulsificação , Humanos , Pessoa de Meia-Idade , Idoso , Implante de Lente Intraocular , Visão Monocular , Acuidade Visual , Refração Ocular , Desenho de Prótese , Satisfação do Paciente , Visão BinocularRESUMO
BACKGROUND: Glioma is caused by multiple genomic alterations. The evolving classification of gliomas emphasizes the significance of molecular testing. Next generation sequencing (NGS) offers the assessment of parallel combinations of multiple genetic alterations and identifying actionable mutations that guide treatment. This study comprehensively analyzed glioma patients using multi-gene NGS panels, providing powerful insights to inform diagnostic classification and targeted therapies. METHODS: We conducted a targeted panel-based NGS analysis on formalin-fixed and paraffin-embedded nucleic acids extracted from a total of 147 glioma patients. These samples underwent amplicon capture-based library preparation and sequenced using the Oncomine Comprehensive Assay platform. The resulting sequencing data were then analyzed using the bioinformatics tools. RESULTS: A total of 301 mutations, were found in 132 out of 147 tumors (89.8%). These mutations were in 68 different genes. In 62 tumor samples (42.2%), copy number variations (CNVs) with gene amplifications occurred in 25 genes. Moreover, 25 tumor samples (17.0%) showed gene fusions in 6 genes and intragenic deletion in a gene. Our analysis identified actionable targets in several genes, including 11 with mutations, 8 with CNVs, and 3 with gene fusions and intragenic deletion. These findings could impact FDA-approved therapies, NCCN guideline-based treatments, and clinical trials. CONCLUSION: We analyzed precisely diagnosing the classification of gliomas, detailing the frequency and co-occurrence of genetic alterations and identifying genetic alterations with potential therapeutic targets by NGS-based molecular analysis. The high-throughput NGS analysis is an efficient and powerful tool to comprehensively support molecular testing in neurooncology.
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PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.
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Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Bacteriemia/mortalidade , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Fatores de RiscoRESUMO
Stressful circumstances are significant contributors to mental illnesses such as major depressive disorder. Anhedonia, defined as loss of the ability to enjoy pleasure in pleasurable situations, including rewarding activities or social contexts, is considered a key symptom of depression. Although stress-induced depression is associated with anhedonia in humans and animals, the underlying molecular mechanisms of anhedonic responses remain poorly understood. In this study, we demonstrated that synaptotagmin-4 (SYT4), which is involved in the release of neurotransmitters and neurotrophic factors, is implicated in chronic stress-induced anhedonia. Employing chronic unpredictable stress (CUS), we evaluated two subpopulations of mice, susceptible (SUS, anhedonic) and resilient (RES, nonanhedonic), based on sucrose preference, which was strongly correlated with social reward. The FosTRAP (targeted recombination in active populations) system and optogenetic approach revealed that neural activity in the medial prefrontal cortex (mPFC) was significantly associated with CUS-induced anhedonic behavioral phenotypes. By conducting weighted gene coexpression network analysis of RNA sequencing data from the mPFC of SUS and RES mice, we identified Syt4 as a hub gene in a gene network that was unique to anhedonia. We also confirmed that Syt4 overexpression in the mPFC was pro-susceptible, while Syt4 knockdown was pro-resilient; the pro-susceptible effects of SYT4 were mediated through a reduction in brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the mPFC. These findings suggest that SYT4-BDNF interactions in the mPFC represent a crucial regulatory mechanism of anhedonic susceptibility to chronic stress.
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Anedonia , Fator Neurotrófico Derivado do Encéfalo , Transtorno Depressivo Maior , Animais , Humanos , Camundongos , Fator Neurotrófico Derivado do Encéfalo/genética , Citoplasma , Córtex Pré-FrontalRESUMO
OBJECTIVES: To explore the clinical effect of Yang's pricking-cupping therapy and its central mechanism in treatment of eczema-induced pruritus using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Fifty patients with eczema-induced pruritus were enrolled in the observation group, and 50 healthy subjects were enrolled in the control group. No any intervention was delivered in the control group. Yang's pricking-cupping therapy was operated at Dazhui (GV 14) and bilateral Quchi (LI 11), Xuehai (SP 10) and Sanyinjiao (SP 6), once a week, lasting 6 weeks in the observation group. The scores of the 12-item pruritus severity scale (12-PSS), the eczema area and severity index (EASI), the dermatology life quality index (DLQI), the Pittsburgh sleep quality index (PSQI), and the self-rating anxiety scale (SAS) were compared before and after treatment in the observation group. The rs-fMRI scanning was conducted and the regional homogeneity (ReHo) analysis performed in all of the participants before and after treatment in the observation group, as well as at the time of subject enrollment in the control group. The correlation was analyzed between ReHo values in the different areas of the brain and the scores of the above scales. RESULTS: Compared with those before treatment, the scores of 12-PSS, EASI, DLQI, PSQI, and SAS were reduced after treatment in the observation group (P<0.01, P<0.05). ReHo values were increased in the right caudate nucleus, the right middle temporal gyrus, the right orbitofrontal gyrus, the right thalamus and the left angular gyrus before treatment in the observation group when compared with those in the control group (P<0.001); and ReHo values in the above areas of the brain were decreased after treatment when compared with those before treatment in the observation group (P<0.001). In comparison with the control group, ReHo values were reduced in the left middle temporal gyrus, the left superior parietal lobule and the left supplementary motor area in the observation group before treatment (P<0.001); while when compared with those before treatment, ReHo values in the above areas of the brain were elevated after treatment in the observation group (P<0.001). Before treatment, ReHo value in the left supplementary motor area was positively correlated with 12-PSS score (r=0.432, P=0.004), and the value in the right orbitofrontal gyrus was negatively correlated with PSQI score (r=-0.318, P=0.04) in the observation group. After treatment, ReHo value in the left superior parietal lobule was positively correlated with 12-PSS score (r=0.384, P=0.012) in the observation group. CONCLUSIONS: The abnormal cerebral functional activities are exhibited in multiple areas of the brain involved in stimulus response, emotional regulation, behavior control and attention in the patients with eczema-induced pruritus. Yang's pricking-cupping therapy can effectively relieve the pruritus symptoms and skin lesions of the patients, which may be related to reversing the abnormal cerebral functional activities induced by pruritus.
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Ventosaterapia , Eczema , Humanos , Imageamento por Ressonância Magnética , Prurido/diagnóstico por imagem , Prurido/etiologia , Prurido/terapia , Eczema/diagnóstico por imagem , Eczema/terapia , Encéfalo/diagnóstico por imagemRESUMO
Eccrine syringofibroadenoma (ESFA) is a tumor of eccrine ductal differentiation. ESFA is a rare disease, with only approximately 80 cases reported worldwide. ESFA can be classified into five subtypes. Senile gluteal dermatosis (SGD) was first reported in Japan in 1979. It is a relatively common geriatric dermatosis in East Asia, and characterized by hyperkeratotic lichenified skin lesions in the gluteal region. An 86-year-old woman presented with a solitary recurrent dark brown plaque in the sacral area. There was a hyperkeratotic lichenified brownish patch around the plaque, which was clinically considered SGD. Histopathological examination of biopsy specimen revealed thin anastomosing reticulated strands of basaloid cuboidal cells. The tumor extends from the basal layer of the epidermis to the dermis. These findings are consistent with those of ESFA. The patient was treated with total excision of the skin lesion. Reactive ESFA is related to tissue regeneration and remodeling after damage, such as trauma and burns. There is no literature reporting ESFA related to SGD so far, but there have been few reports of cases occurring in soles or buttocks, which are constantly under pressure. This is the first report on reactive ESFA related to SGD, and further research is needed to reveal the pathogenic mechanism.
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Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD). Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.
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In East Asia, severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus, which are common endemic tick- and mite-mediated diseases sharing common clinical manifestations, are becoming public health concerns. However, there are limited data on the comparative immunopathogenesis between the two diseases. We compared the cytokine profiles of SFTS and scrub typhus to further elucidate immune responses that occur during the disease courses. We prospectively enrolled 44 patients with confirmed SFTS and 49 patients with scrub typhus from July 2015 to December 2020. In addition, 10 healthy volunteers were enrolled as healthy controls. A cytometric bead array was used to analyze plasma samples for 16 cytokines. A total of 68 plasma samples, including 31 (45.6%) from patients with SFTS and 37 (54.4%) from patients with scrub typhus, were available for cytokine measurement. There were three cytokine expression patterns: increased levels in both SFTS and scrub typhus (interleukin 6 [IL-6], IL-10, interferon gamma induced protein 10 [IP-10], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), highest levels in SFTS (interferon alpha [IFN-α], IFN-γ, granulocyte-CSF [G-CSF], monocyte chemotactic protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], and IL-8), and distinct levels in scrub typhus (IL-12p40, tumor necrosis factor alpha [TNFα], IL-1ß, regulated on activation and normally T-cell expressed and secreted [RANTES], IL-17A, and vascular endothelial growth factor [VEGF]). Although patients with acute SFTS and scrub typhus exhibited partly shared expression patterns of cytokines related to disease severity, the different profiles of cytokines and chemokines might contribute to higher mortality in SFTS than in scrub typhus. Discrete patterns of helper T cell-related cytokines and VEGF might reflect differences in CD4 T-cell responses and vascular damage between these diseases.
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Phlebovirus , Tifo por Ácaros , Febre Grave com Síndrome de Trombocitopenia , Humanos , Quimiocinas , Citocinas , República da Coreia , Fator A de Crescimento do Endotélio Vascular , Estudos ProspectivosRESUMO
Background: The Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS) is largely used for assessing disease activity in patients with AS. Objectives: We aimed to investigate the predictability of ASDAS on drug survival in patients with low Bath AS Disease Activity Index (BASDAI) during biologic therapy. Design: Using data from multi-center, prospective, observational prospective cohort, Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Methods: The study population consisted of patients enrolled in the KOBIO registry from December 2012 to December 2018. The baseline demographic data and variables such as extra-articular manifestations, HLA-B27 positivity, family history of spondyloarthritis, ASDAS C-reactive protein (CRP), BASDAI, and Bath AS Functional Index scores were collected from the database. The disease activity indices were followed yearly after initiating a tumor necrosis factor (TNF) inhibitor (TNFi). Disease activities were defined as high (ASDAS-CRP ⩾ 2.1, BASDAI ⩾ 4) and low (ASDAS-CRP < 2.1, BASDAI < 4). Results: Data from 1773 patients were analyzed. Among 269 patients with low BASDAI at baseline, 151 (56.1%) patients had high ASDAS-CRP, yet in 142 patients with low ASDAS-CRP at baseline, only 24 (16.9%) patients had a high BASDAI. High ASDAS-CRP captured more patients who had initiated or switched to a TNFi than those with high BASDAI (92.5% versus 84.8%, respectively, p < 0.001). Moreover, among AS patients with low BASDAI after 1 year of therapy, drug persistence in the following year was significantly lower in patients with high ASDAS than in those with low ASDAS (68.7% versus 82.5%, p < 0.001). Conclusion: ASDAS-CRP not only has its advantages over BASDAI in assessing disease activity but also low ASDAS-CRP at 1 year can be a marker of long-term drug survival of TNFi therapy.
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Introduction: This study examines how teacher support and practicum stress affect art therapy graduate students' burnout. Methods: A total of 125 master's and doctoral students from art therapy graduate schools in Korea participated in the study. We conducted a correlation analysis and multiple regression analysis to explore the relationship between the variables. Results: The correlation analysis results showed that burnout, practicum stress, and social support are significantly interrelated. The regression analysis results indicated that practicum stress increases burnout while social support decreases it. When we used the sub-factors of social support as independent variables, we found that professor support rather than the support of colleagues or family significantly reduced burnout. When we divided the perceived teacher support into emotional support and academic support, our analysis identified that academic support was more important than emotional support to reduce students' burnout. Conclusion: Art therapy students' practicum stress can cause psychological burnout, while teacher support-especially academic support-can lower the possibility of experiencing such burnout.
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The monoamine hypothesis has significantly improved our understanding of mood disorders and their treatment by linking monoaminergic abnormalities to the pathophysiology of mood disorders. Even 50 years after the monoamine hypothesis was established, some patients do not respond to treatments for depression, including selective serotonin reuptake drugs. Accumulating evidence shows that patients with treatment-resistant depression (TRD) have severe abnormalities in the neuroplasticity and neurotrophic factor pathways, indicating that different treatment approaches may be necessary. Therefore, the glutamate hypothesis is gaining attention as a novel hypothesis that can overcome monoamine restrictions. Glutamate has been linked to structural and maladaptive morphological alterations in several brain areas associated with mood disorders. Recently, ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has shown efficacy in TRD treatment and has received the U.S. Food and Drug Administration approval, revitalizing psychiatry research. However, the mechanism by which ketamine improves TRD remains unclear. In this review, we re-examined the glutamate hypothesis, bringing the glutamate system onboard to join the modulation of the monoamine systems, emphasizing the most prominent ketamine antidepressant mechanisms, such as NMDAR inhibition and NMDAR disinhibition in GABAergic interneurons. Furthermore, we discuss the animal models used in preclinical studies and the sex differences in the effects of ketamine.
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BACKGROUND: Facial erythema is a common problem among patients visiting dermatologists. However, data on the clinical characteristics of facial erythema in healthy people are lacking. We aimed to compare and analyze the severity and pattern of facial vascularity in healthy subjects based on their age and gender. MATERIALS AND METHODS: This study included 198 Korean volunteers (126 females and 72 males) with Fitzpatrick skin types II, III, or IV. Fourteen different anatomical areas on the face were divided into facial erythema units. Each unit was scored from one (least erythematous) to five (most erythematous) according to the observed level of erythema on the red images implemented as hemoglobin content. We also evaluated the presence of facial telangiectatic macules. RESULTS: On average, the perinasal, nasal, and cheek units were the most hypervascular regions. In contrast, the degree of facial erythema was lowest in the labial (perioral), neck, and temporal regions. The average value of erythema was higher in males than in females. Additionally, the severity of erythema tended to increase with age. In both males and females, the number of telangiectatic macules increased with age. CONCLUSIONS: We analyzed the clinical characteristics of erythema in healthy subjects with Fitzpatrick skin types II, III, or IV in the Korean population. This study is expected to be used to identify the neurovascular pathogenesis of the most common regions of facial dermatosis in the future.
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Face , Dermatoses Faciais , Telangiectasia , Feminino , Humanos , Masculino , Povo Asiático , Eritema/patologia , República da Coreia/epidemiologia , Voluntários Saudáveis , Face/irrigação sanguíneaRESUMO
The synthesis of functionalized carbazoles as privileged nitrogen heterocycles has emerged as a central topic in drug discovery and material science. We herein disclose the rhodium(III)-catalyzed cross-coupling reaction between indolyl nitrones and 2-methylidene cyclic carbonate as an allylating surrogate, resulting in the formation of C2-formylated carbazoles via tandem C-H allylation, [3 + 2] cycloaddition, aromatization, and benzylic oxidation. The synthetic utility of this protocol is highlighted by a variety of post-transformations of C2-formylated carbazoles.
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Carbazóis , Óxidos de Nitrogênio , Catálise , CarbonatosRESUMO
Background: Severe respiratory syncytial virus (RSV)-associated pneumonia in adults has rarely been addressed. We investigated the burden and clinical characteristics of severe RSV-associated pneumonia in critically ill adult patients. Methods: We analyzed a prospective cohort of 2865 adults with severe pneumonia who were admitted to the intensive care unit in a 2700-bed tertiary care hospital from 2010 to 2019. The epidemiology, characteristics, and outcomes of 92 cases of severe RSV-associated pneumonia and 163 cases of severe influenza virus (IFV)-associated pneumonia were compared. Results: Of 1589 cases of severe community-acquired pneumonia, the incidence of RSV-associated pneumonia was less than half that of IFV-associated pneumonia (3.4% vs 8.1%). However, among 1276 cases of severe hospital-acquired pneumonia (HAP), there were slightly more cases of RSV-associated than IFV-associated pneumonia (3.8% vs 3.5%). During the 9 epidemic seasons, RSV-A (5 seasons) and RSV-B (4 seasons) predominated alternately. Structural lung disease, diabetes mellitus, and malignancy were common underlying diseases in both groups. Immunocompromise (57.6% vs 34.4%; P < .001) and hospital acquisition (47.8% vs 23.9%; P < .001) were significantly more common in the RSV group. Coinfection with Streptococcus pneumoniae (3.3% vs 9.8%; P = .08) and methicillin-susceptible Staphylococcus aureus (1.1% vs 6.8%; P = .06) tended to be less frequent in the RSV group. The 90-day mortality was high in both groups (39.1% vs 40.5%; P = .89). Conclusions: RSV infection was associated with substantial morbidity and mortality in critically ill adult patients, similar to IFV. The relatively higher incidence of RSV in severe HAP suggests that the transmissibility of RSV can exceed that of IFV in a hospital setting.
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Dispersive liquid-liquid microextraction was used in conjunction with liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry to quantitate vitamins K1 and K2 in vitamin-fortified emulsions, and vital microextraction parameters were optimized using response surface methodology coupled with Box-Behnken design. Under optimal microextraction conditions, highly linear (R 2 > .999) calibration curves were obtained for both vitamins in a broad concentration range (1-1000 µg/L), and vitamin recoveries exceeded 90%. The detection and quantitation limits equaled 1.89 and 5.72 µg/L for vitamin K1, respectively, and 5.00 and 15.15 µg/L for vitamin K2, respectively. When applied to vitamin-K-loaded nanoemulsions and solid lipid nanoparticles, the developed method achieved excellent results, outperforming the currently employed Korean Food Code method, and therefore holding great promise for the quantitation of vitamin K in vitamin-fortified food products.
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Background: Limited data is available between metabolic syndrome (MetS) and the development of peripheral arterial disease (PAD) or venous thromboembolism (VTE) in the Asian population. We investigated the incidence of PAD and VTE according to the prevalence of MetS and evaluated the impact of individual components in MetS on the development of PAD and VTE using Korean national data. Methods: Data obtained from national health screening examinations of the Korean National Health Insurance Service from January 1, to December 31, 2009. In total, 9,927,538 participants, 7,830,602 participants were included in this study and the incidence rate of PAD and VTE was investigated retrospectively during a 7-year follow-up. Using the National Cholesterol Education Program Adult Treatment Panel III criteria, patients were placed into one of three groups depending on MetS component numbers: 0 (normal), 1-2 (Pre-MetS), or 3-5 (MetS). Results: The incidence rates of PAD and VTE in MetS were 2.25% and 0.71%, respectively. After multivariable adjustment, the risk of PAD was significantly associated with MetS (hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.42-1.49), the risk of VTE was not associated with MetS (HR 1.01, 95% CI 0.96-1.05). When subgroup analyses were conducted according to MetS components, elevated fasting glucose (HR 1.26, 95% CI 1.23-1.27), abdominal obesity (HR 1.15, 95% CI 1.12-1.17), and elevated blood pressure (HR 1.13, 95% CI 1.12-1.15) were the most related to PAD. Abdominal obesity (HR 1.104, 95% CI 1.064-1.146) was associated with an increased risk of VTE. Conclusions: MetS was significantly associated with an increased incidence rate of PAD among the general Korean population. On the other hand, MetS was not associated with the VTE incidence rate. Of the MetS components, only abdominal obesity was a significant predictor of VTE.