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1.
Bioresour Technol ; 352: 127079, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35367324

RESUMO

To apply the anammox processes into the mainstream of domestic wastewater treatment plants, two laboratory-scale sequence batch reactors have been developed and used with two different activated sludges seeded in each sequence batch reactors with gradually increases influent total nitrogen concentrations under low nitrogen loading rates. During 320 days of operation, both sequence batch reactors showed high specific anammox activity (0.68 - 0.75 kgN kg-1VSS d-1) and a nitrogen removal efficiency of 97.50%. To monitor changes in microbial community dynamics during enrichment, high-throughput sequencing analysis was performed. Members taxonomically affiliated with Candidatus Jettenia were markedly enriched and predominant in both sequence batch reactors in response to the increasing influent total nitrogen concentrations. These results suggest that Candidatus Jettenia might be a prominent anammox genus under low nitrogen loading rate with high total nitrogen concentration conditions and could be suitably applied to the mainstream process of domestic wastewater treatment systems.


Assuntos
Reatores Biológicos , Nitrogênio , Anaerobiose , Nitrogênio/análise , Oxirredução , Esgotos , Águas Residuárias/análise
2.
J Reconstr Microsurg ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35426085

RESUMO

INTRODUCTION: Despite the extensive use of various imaging modalities, there is limited literature on comparing the reliability between indocyanine green (ICG) lymphography, MR Lymphangiogram (MRL), and high frequency color Doppler ultrasound (HFCDU) to identify lymphatic vessels. METHOD: In this study of 124 patients, the correlation between preoperative image findings to the actual lymphatic vessel leading to lymphovenous anastomosis (LVA) was evaluated. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and simple detection were calculated. Subgroup analysis was also performed according to the severity of lymphedema. RESULTS: Total of 328 LVAs were performed. The HFCDU overall had significantly higher sensitivity for identifying lymphatic vessels (99%) over MRL (83.5%) and ICG lymphography (82.3%)(p < 0.0001). Both ICG lymphography and HFCDU had 100% specificity and PPV. The NPV was 3.6%, 6.5% and 57.1% respectively for MRL, ICG lymphography, and HFCDU. All modalities showed high sensitivity for early stage 2 lymphedema while HFCDU showed a significantly higher sensitivity for late stage 2 (MRL:79.7%, ICG:83.1%, HFCDU:97%) and stage 3 (MRL:79.7%, ICG:79.7%, HFCDU:100%) over the other two modalities (p < 0.0001). CONCLUSION: This study demonstrated while all three modalities are able to provide good information, the sensitivity may alter as the severity of lymphedema progresses. The HFCDU will provide the best detection for lymphatic vessels throughout all stages of lymphedema. However, as each modality provides different and unique information, combining and evaluating the data according to the stage of lymphedema will be able to maximize the chance for a successful surgical outcome.

3.
Transl Lung Cancer Res ; 11(1): 14-23, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35242624

RESUMO

BACKGROUND: Thoracic lymph node (LN) evaluation is essential for the accurate diagnosis of lung cancer and deciding the appropriate course of treatment. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered a standard method for mediastinal nodal staging. This study aims to build a deep convolutional neural network (CNN) for the automatic classification of metastatic malignancies involving thoracic LN, using EBUS-TBNA. METHODS: Patients who underwent EBUS-TBNAs to assess the presence of malignancy in mediastinal LNs during a ten-month period at Severance Hospital, Seoul, Republic of Korea, were included in the study. Corresponding LN ultrasound images, pathology reports, demographic data, and clinical history were collected and analyzed. RESULTS: A total of 2,394 endobronchial ultrasound (EBUS) images of 1,459 benign LNs from 193 patients, and 935 malignant LNs from 177 patients, were collected. We employed the visual geometry group (VGG)-16 network to classify malignant LNs using only traditional cross-entropy for classification loss. The sensitivity, specificity, and accuracy of predicting malignancy were 69.7%, 74.3%, and 72.0%, respectively, and the overall area under the curve (AUC) was 0.782. We applied the new loss function to train the network and, using the modified VGG-16, the AUC improved to a value of 0.8. The sensitivity, specificity, and accuracy improved to 72.7%, 79.0%, and 75.8%, respectively. In addition, the proposed network can process 63 images per second on a single mainstream graphics processing unit (GPU) device, making it suitable for real-time analysis of EBUS images. CONCLUSIONS: Deep CNNs can effectively classify malignant LNs from EBUS images. Selecting LNs that require biopsy using real-time EBUS image analysis with deep learning is expected to shorten the EBUS-TBNA procedure time, increase lung cancer nodal staging accuracy, and improve patient safety.

4.
Exp Neurobiol ; 31(1): 29-41, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35256542

RESUMO

Abnormal aggregation of α-synuclein is a key element in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-synuclein aggregation spreads through various brain regions during the course of disease progression, a propagation that is thought to be mediated by the secretion and subsequent uptake of extracellular α-synuclein aggregates between neuronal cells. Thus, aggregated forms of this protein have emerged as promising targets for disease-modifying therapy for PD and related diseases. Here, we generated and characterized conformation-specific antibodies that preferentially recognize aggregated forms of α-synuclein. These antibodies promoted phagocytosis of extracellular α-synuclein aggregates by microglial cells and interfered with cell-to-cell propagation of α-synuclein. In an α-synuclein transgenic model, passive immunization with aggregate-specific antibodies significantly ameliorated pathological phenotypes, reducing α-synuclein aggregation, gliosis, inflammation, and neuronal loss. These results suggest that conformation-specific antibodies targeting α-synuclein aggregates are promising therapeutic agents for PD and related synucleinopathies.

5.
Respir Res ; 23(1): 73, 2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35346198

RESUMO

BACKGROUND: For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model. METHODS: Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV ± DMSO; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 µL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 and EphA2 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined. RESULTS: Cell counts from BALFs were significantly lower in the NOX4 KO with HTV group (p < 0.01) and EphA2 KO with HTV group (p < 0.001) compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p < 0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p < 0.001). In patients with respiratory disease, NOX4 and EphA2 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit. CONCLUSION: In the VILI model with high tidal volume, NOX4 KO, EphA2 KO or monoclonal antibodies attenuated the VILI. NOX4 and EphA2 levels were significantly higher in patients with pneumonia and especially in mechanical ventilated in the ICU. Inhibition of Nox4 is a potential therapeutic target for the prevention and reduction of VILI.


Assuntos
NADPH Oxidase 4 , Lesão Pulmonar Induzida por Ventilação Mecânica , Animais , Humanos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Transdução de Sinais , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo
6.
Ann Dermatol ; 34(1): 1-6, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35221588

RESUMO

BACKGROUND: The morphology of hair regrowth in alopecia areata (AA) patches could be classified into four types, namely diffuse, irregular, marginal, and targetoid patterns, according to the DIMT classification. However, factors affecting hair regrowth patterns have not been investigated. OBJECTIVE: We investigated whether the DIMT-classified hair regrowth patterns of AA patches are associated with treatment modality and patch size. METHODS: We conducted a retrospective, cross-sectional study of 152 AA patches with hair regrowth. RESULTS: The associations between the diffuse pattern and patch size >2 cm (p=0.006; odds ratio [OR]: 0.36, 95% confidence interval [CI]: 0.17~0.74), between the irregular pattern and triamcinolone acetonide intralesional injection (p<0.001; OR: 274.87, 95% CI: 25.75~2,933.56), between the marginal pattern and systemic and topical corticosteroid (p=0.018; OR: 4.89, 95% CI: 1.31~18.27), and between the targetoid pattern and patch size >2 cm (p=0.028; OR: 2.50, 95% CI: 1.10~5.68) were statistically significant. CONCLUSION: Treatment modalities and patch size are the factors affecting hair regrowth patterns in AA patches.

7.
Int J Rheum Dis ; 25(5): 523-531, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35187866

RESUMO

AIM: To provide in-depth understanding of real-world tumor necrosis factor inhibitor (TNFi) treatment patterns in patients with ankylosing spondylitis (AS) and treatment satisfaction, productivity loss, and associated factors. METHODS: This was a multicenter observational hybrid retrospective chart review and cross-sectional survey study. Disease activity and physical functioning were measured using the Bath AS Disease Activity Index and Bath AS Functional Index, respectively. Treatment satisfaction was determined with the Treatment Satisfaction Questionnaire for Medication (TSQM). Productivity loss was evaluated using the Korean version of the World Health Organization-Health and Work Performance Questionnaire. RESULTS: A total of 497 patients were enrolled (mean age 40.3 years, 85.3% male, mean AS duration 10 years). The mean duration of TNFi treatment was 6.2 years. Among the four TNFi considered, adalimumab (39.6%) and etanercept (23.5%) were most commonly used at study enrollment. The TSQM convenience domain score was lower than scores in the effectiveness, adverse effects, and global satisfaction domains. Subcutaneous syringe-type injection and intravenous injection were associated with lower patient convenience satisfaction than subcutaneous pen-type injection. Increased costs of lost productivity time were associated with female sex, unemployed status, and higher disease activity. CONCLUSIONS: The most frequently prescribed TNFi was adalimumab, followed by etanercept. Etanercept was used for the longest duration. More convenient treatment options may enhance overall treatment satisfaction. Considerable loss in productivity due to AS was observed in this study. To reflect patients' perspectives, further attention should be paid to factors associated with treatment satisfaction and productivity loss when selecting treatment options.


Assuntos
Antirreumáticos , Espondilite Anquilosante , Adalimumab/efeitos adversos , Adulto , Antirreumáticos/efeitos adversos , Estudos Transversais , Etanercepte/efeitos adversos , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Satisfação do Paciente , Satisfação Pessoal , República da Coreia , Estudos Retrospectivos , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/tratamento farmacológico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Fator de Necrose Tumoral alfa
8.
Anticancer Res ; 42(3): 1615-1622, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220259

RESUMO

BACKGROUND/AIM: Non-small cell lung cancers (NSCLCs) harboring uncommon epidermal growth factor receptor (EGFR) mutations are heterogeneous and show variable prevalence and clinical responses to EGFR tyrosine kinase inhibitors. We investigated the characteristics of uncommon EGFR mutations and the clinical efficacy of afatinib in patients with NSCLC harboring uncommon EGFR mutations. PATIENTS AND METHODS: In this multicenter, retrospective study, we analyzed patients with NSCLC with uncommon EGFR mutations in 16 South Korean institutes. Mutations were categorized according to their incidence: 1) major uncommon mutations (G719X and L861Q), 2) compound mutations, and 3) minor uncommon mutations (exon 20 insertion, S768I, and de novo T790M). RESULTS: Of 703 patients with EGFR-mutant NSCLC, 64 (9.1%) had uncommon EGFR mutations. Afatinib demonstrated activity against tumors harboring major uncommon mutations [median time of treatment (TOT): 20.3 months, 95% confidence interval (CI)=15.1-25.5; overall survival (OS): 30.6 months, 95% CI=26.3-34.8] and compound mutations (median TOT: 12.3 months, 95% CI=7.7-17.0; OS: 29.1 months, 95% CI=20.4-37.7) but not against tumors harboring minor uncommon mutations (median TOT: 3.8 months, 95% CI=1.7-6.0; OS: 8.5 months, 95% CI=5.2-11.7). The S768I mutation was present in 14 patients (1.99%). The median TOT and OS were not significantly different between S768I mutations and resistant exon 20 mutations. CONCLUSION: Afatinib is effective in patients with NSCLC harboring major uncommon and compound EGFR mutations.


Assuntos
Afatinib/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Afatinib/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Éxons , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Seul , Fatores de Tempo , Resultado do Tratamento
9.
J Cachexia Sarcopenia Muscle ; 13(2): 955-965, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35170229

RESUMO

BACKGROUND: Diagnostic cutoff points for sarcopenia in chest computed tomography (CT) have not been established although CT is widely used for investigating skeletal muscles. This study aimed to determine reference values for sarcopenia of thoracic skeletal muscles acquired from chest CT scans and to analyse variables related to sarcopenia using the cutoff values determined in a general Asian population. METHODS: We retrospectively reviewed chest CT scans of 4470 participants (mean age 54.8 ± 9.9 years, 65.8% male) performed at a check-up centre in South Korea (January 2016-August 2017). To determine cutoffs, 335 participants aged 19-39 years (mean age 35.2 ± 3.6 years, 75.2% male) were selected as the healthy and younger reference group, and 4135 participants aged ≥40 years (mean age 56.4 ± 8.4 years, 65.1% male) were selected as the study group. We measured the following: cross-sectional area (CSA) of the pectoralis, intercostalis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA ); T4CSA divided by height2 (T4MI); pectoralis muscle area (PMCSA ); and PMCSA divided by height2 (PMI) at the 4th vertebral region. Sarcopenia cutoff was defined as sex-specific values of less than -2 SD below the mean from the reference group. RESULTS: In the reference group, T4CSA , T4MI, PMCSA , and PMI cutoffs for sarcopenia were 100.06cm2 , 33.69cm2 /m2 , 29.00cm2 , and 10.17cm2 /m2 in male, and 66.93cm2 , 26.01cm2 /m2 , 18.29cm2 , and 7.31cm2 /m2 in female, respectively. The prevalence of sarcopenia in the study group measured with T4CSA , T4MI, PMCSA and PMI cutoffs were 11.4%, 8.7%, 8.5%, and 10.1%, respectively. Correlations were observed between appendicular skeletal mass divided by height2 measured by bioelectrical impedance analysis (BIA) and T4CSA (r = 0.82; P < 0.001)/T4MI (r = 0.68; P < 0.001), and ASM/height2 measured by BIA and PMCSA (r = 0.72; P < 0.001)/PMI (r = 0.63; P < 0.001). In the multivariate logistic regression models, sarcopenia defined by T4CSA /T4MI were related to age [odds ratio (95% confidence interval), P-values: 1.09 (1.07-1.11), <0.001/1.05 (1.04-1.07), <0.001] and diabetes [1.60 (1.14-2.25), 0.007/1.47 (1.01-2.14), 0.043]. Sarcopenia defined by PMCSA /PMI were related to age [1.09 (1.08-1.10), <0.001/1.05 (1.03-1.06), <0.001], male sex [0.23 (0.18-0.30), <0.001/0.47 (0.32-0.71), <0.001], diabetes [2.30 (1.73-3.05), <0.001/1.63 (1.15-2.32), 0.007], history of cancer [2.51 (1.78-3.55), <0.001/1.61 (1.04-2.48), 0.033], and sufficient physical activity [0.67 (0.50-0.89), 0.007/0.74 (0.56-0.99), 0.042]. CONCLUSIONS: The reference cutoff values of a general population reported here will enable sex-specific standardization of thoracic muscle mass quantification and sarcopenia assessment.


Assuntos
Sarcopenia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Valores de Referência , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , Tomografia Computadorizada por Raios X , Adulto Jovem
10.
Medicina (Kaunas) ; 58(2)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35208579

RESUMO

Background and objectives: Acute cholangitis can be life-threatening if not recognized early. We investigated the predictive value of the neutrophil-lymphocyte ratio (NLR) in acute cholangitis. Materials and Methods: We retrospectively evaluated 206 patients with acute cholangitis who underwent biliary drainage. The severity of acute cholangitis was graded according to the Tokyo 2018 guideline. Patients were dichotomized according to the acute cholangitis severity (mild/moderate vs. severe), the presence of shock requiring a vasopressor/inotrope, and blood culture positivity. The baseline NLR, white blood cell (WBC) count, and C-reactive protein (CRP) levels were compared between groups. Results: The severity of acute cholangitis was graded as mild, moderate, or severe in 71 (34.5%), 107 (51.9%), and 28 (13.6%) patients, respectively. Ten patients (4.8%) developed shock. Positive blood culture (n = 50) was observed more frequently in severe acute cholangitis (67.9% vs. 17.4%, p < 0.001). The NLR was significantly higher in patients with severe cholangitis, shock, and positive blood culture. The area under the curve (AUC) for the NLR, WBC, and CRP for severe acute cholangitis was 0.87, 0.73, and 0.74, respectively. The AUC for the NLR, WBC, and CRP for shock was 0.81, 0.64, and 0.67, respectively. The AUC for the NLR, WBC, and CRP for positive blood culture was 0.76, 0.64, and 0.61, respectively; the NLR had greater power to predict disease severity, shock, and positive blood culture. The optimal cut-off value of the baseline NLR for the prediction of severe acute cholangitis, shock, and positive blood culture was 15.24 (sensitivity, 85%; specificity, 79%), 15.54 (sensitivity, 80%; specificity, 73%), and 12.35 (sensitivity, 72%; specificity, 70%), respectively. The sequential NLR values from admission to 2 days after admission were significantly higher in patients with severe cholangitis and shock. Conclusions: An elevated NLR correlates with severe acute cholangitis, shock, and positive blood culture. Serial NLR can track the clinical course of acute cholangitis.


Assuntos
Colangite , Neutrófilos , Proteína C-Reativa/análise , Humanos , Contagem de Leucócitos , Linfócitos , Curva ROC , Estudos Retrospectivos
11.
Pain Physician ; 25(1): E141-E145, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35051162

RESUMO

BACKGROUND: Neuropathic pain in the hands due to carpal tunnel syndrome (CTS) disturbs sleep and affects the quality of life. OBJECTIVES: We evaluated the effect of ultrasound (US)-guided partial release of the transverse carpal ligament (TCL) using an 18-G needle in patients with refractory CTS. STUDY DESIGN: A prospective outcome study. SETTING: The outpatient clinic of a single academic medical center. METHODS: This study was prospectively conducted. A total of 155 consecutive patients (191 wrists) with refractory chronic CTS (M:F = 28:127; age = 54.7 ± 9.6 years; pain duration = 50.3 ± 36.3 weeks) were enrolled and underwent US-guided partial release of the TCL using a needle. The pain severity was measured using the Numeric Rating Scale (NRS) at 3 and 6 months after the treatment. Successful treatment outcomes were defined as more than 50% reduction in the NRS score at 6 months after the treatment compared with the score at pre-treatment and NRS score < 3 at 6 months after the treatment without any surgical intervention. RESULTS: There were 3 dropouts, and 188 wrists were included in the study. No side effects were reported. A total of 162 wrists (86.2%) showed successful treatment outcomes at 6 months after TCL release. Of the 26 wrists which had unsuccessful treatment outcomes, 6 received surgical treatment. The NRS scores at 3- and 6-month post-treatment were significantly reduced: the average NRS scores were 7.1 ± 0.6 at baseline, 1.9 ± 1.7 at 3 months after the treatment, and 1.7 ± 1.7 at 6 months after the treatment. LIMITATIONS: We conducted our study without a control or a placebo group. CONCLUSION: We believe that US-guided partial release of the TCL using a needle can be an effective and safe technique for treating chronic refractory pain due to CTS. It can potentially be attempted before surgical treatment.


Assuntos
Síndrome do Túnel Carpal , Síndrome do Túnel Carpal/cirurgia , Humanos , Ligamentos Articulares/cirurgia , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Ultrassonografia de Intervenção/métodos
12.
Proc Natl Acad Sci U S A ; 119(3)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35022233

RESUMO

Synaptic cell-adhesion molecules (CAMs) organize the architecture and properties of neural circuits. However, whether synaptic CAMs are involved in activity-dependent remodeling of specific neural circuits is incompletely understood. Leucine-rich repeat transmembrane protein 3 (LRRTM3) is required for the excitatory synapse development of hippocampal dentate gyrus (DG) granule neurons. Here, we report that Lrrtm3-deficient mice exhibit selective reductions in excitatory synapse density and synaptic strength in projections involving the medial entorhinal cortex (MEC) and DG granule neurons, accompanied by increased neurotransmitter release and decreased excitability of granule neurons. LRRTM3 deletion significantly reduced excitatory synaptic innervation of hippocampal mossy fibers (Mf) of DG granule neurons onto thorny excrescences in hippocampal CA3 neurons. Moreover, LRRTM3 loss in DG neurons significantly decreased mossy fiber long-term potentiation (Mf-LTP). Remarkably, silencing MEC-DG circuits protected against the decrease in the excitatory synaptic inputs onto DG and CA3 neurons, excitability of DG granule neurons, and Mf-LTP in Lrrtm3-deficient mice. These results suggest that LRRTM3 may be a critical factor in activity-dependent synchronization of the topography of MEC-DG-CA3 excitatory synaptic connections. Collectively, our data propose that LRRTM3 shapes the target-specific structural and functional properties of specific hippocampal circuits.


Assuntos
Sincronização Cortical/fisiologia , Hipocampo/fisiologia , Proteínas de Membrana/metabolismo , Rede Nervosa/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Sinapses/fisiologia , Animais , Região CA3 Hipocampal/metabolismo , Giro Denteado/metabolismo , Córtex Entorrinal/metabolismo , Potenciação de Longa Duração , Proteínas de Membrana/deficiência , Camundongos Knockout , Fibras Musgosas Hipocampais/metabolismo , Proteínas do Tecido Nervoso/deficiência , Neurônios/metabolismo , Pseudópodes/metabolismo , Transmissão Sináptica/fisiologia
13.
PLoS One ; 17(1): e0262990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35085358

RESUMO

Whether having a tattoo increases the risk of transfusion-transmitted diseases (TTDs) is controversial. Although a few studies have suggested a strong association between having tattoos and TTDs, other studies have not shown the significance of the association. In addition, previous studies mainly focused only on hepatitis C viral infections. The objective of our study was to identify the prevalence and risk of TTDs in people with tattoos as compared with the non-tattooed population. A systematic review of the studies published before January 22, 2021, was performed using the Pubmed, Embase, and Web of Science databases. Observational studies on hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and syphilis infections in people with and without tattoos were included. Studies that reported disease status without serological confirmation were excluded. A total of 121 studies were quantitatively analyzed. HCV (odds ratio [OR], 2.37; 95% confidence interval [CI], 2.04-2.76), HBV (OR, 1.55; 95% CI, 1.31-1.83), and HIV infections (OR, 3.55; 95% CI, 2.34-5.39) were more prevalent in the tattooed population. In subgroup analyses, the prevalence of HCV infection was significantly elevated in the general population, hospital patient, blood donor, intravenous (IV) drug user, and prisoner groups. IV drug users and prisoners showed high prevalence rates of HBV infection. The prevalence of HIV infection was significantly increased in the general population and prisoner groups. Having a tattoo is associated with an increased prevalence of TTDs. Our approach clarifies in-depth and supports a guideline for TTD screening in the tattooed population.


Assuntos
Infecções por HIV , HIV-1 , Hepacivirus , Vírus da Hepatite B , Hepatite B , Hepatite C , Tatuagem , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Hepatite B/epidemiologia , Hepatite B/transmissão , Hepatite C/epidemiologia , Hepatite C/transmissão , Humanos , Prevalência
14.
Clin Endosc ; 55(1): 163-165, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34974681
15.
BMC Pulm Med ; 22(1): 7, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34996422

RESUMO

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. METHODS: We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. RESULTS: During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). CONCLUSIONS: The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.


Assuntos
Pneumonia por Pneumocystis/complicações , Pneumotórax/complicações , Pneumotórax/epidemiologia , Idoso , Estudos de Coortes , Feminino , Infecções por HIV , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii , Pneumotórax/terapia , Prognóstico , República da Coreia/epidemiologia , Respiração Artificial , Insuficiência Respiratória/complicações , Estudos Retrospectivos , Fatores de Risco
16.
J Neurosci ; 42(9): 1820-1844, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-34992132

RESUMO

Neonatal hydrocephalus presents with various degrees of neuroinflammation and long-term neurologic deficits in surgically treated patients, provoking a need for additional medical treatment. We previously reported elevated neuroinflammation and severe periventricular white matter damage in the progressive hydrocephalus (prh) mutant which contains a point mutation in the Ccdc39 gene, causing loss of cilia-mediated unidirectional CSF flow. In this study, we identified cortical neuropil maturation defects such as impaired excitatory synapse maturation and loss of homeostatic microglia, and swimming locomotor defects in early postnatal prh mutant mice. Strikingly, systemic application of the anti-inflammatory small molecule bindarit significantly supports healthy postnatal cerebral cortical development in the prh mutant. While bindarit only mildly reduced the ventricular volume, it significantly improved the edematous appearance and myelination of the corpus callosum. Moreover, the treatment attenuated thinning in cortical Layers II-IV, excitatory synapse formation, and interneuron morphogenesis, by supporting the ramified-shaped homeostatic microglia from excessive cell death. Also, the therapeutic effect led to the alleviation of a spastic locomotor phenotype of the mutant. We found that microglia, but not peripheral monocytes, contribute to amoeboid-shaped activated myeloid cells in prh mutants' corpus callosum and the proinflammatory cytokines expression. Bindarit blocks nuclear factor (NF)-kB activation and its downstream proinflammatory cytokines, including monocyte chemoattractant protein-1, in the prh mutant. Collectively, we revealed that amelioration of neuroinflammation is crucial for white matter and neuronal maturation in neonatal hydrocephalus. Future studies of bindarit treatment combined with CSF diversion surgery may provide long-term benefits supporting neuronal development in neonatal hydrocephalus.SIGNIFICANCE STATEMENT In neonatal hydrocephalus, little is known about the signaling cascades of neuroinflammation or the impact of such inflammatory insults on neural cell development within the perinatal cerebral cortex. Here, we report that proinflammatory activation of myeloid cells, the majority of which are derived from microglia, impairs periventricular myelination and cortical neuronal maturation using the mouse prh genetic model of neonatal hydrocephalus. Administration of bindarit, an anti-inflammatory small molecule that blocks nuclear factor (NF)-kB activation, restored the cortical thinning and synaptic maturation defects in the prh mutant brain through suppression of microglial activation. These data indicate the potential therapeutic use of anti-inflammatory reagents targeting neuroinflammation in the treatment of neonatal hydrocephalus.


Assuntos
Hidrocefalia , Microglia , Animais , Animais Recém-Nascidos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Feminino , Humanos , Hidrocefalia/tratamento farmacológico , Indazóis , Camundongos , Gravidez , Propionatos
17.
Acad Radiol ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34998683

RESUMO

RATIONALE AND OBJECTIVES: To develop and validate prediction models to differentiate acute and chronic vertebral compression fractures based on radiologic and radiomic features on CT. MATERIALS AND METHODS: This study included acute and chronic compression fractures in patients who underwent both spine CT and MRI examinations. For each fractured vertebra, three CT findings ([1] cortical disruption, [2] hypoattenuating cleft or sclerotic line, and [3] relative bone marrow attenuation) were assessed by two radiologists. A radiomic score was built from 280 radiomic features extracted from non-contrast-enhanced CT images. Weighted multivariable logistic regression analysis was performed to build a radiologic model based on CT findings and an integrated model combining the radiomic score and CT findings. Model performance was evaluated and compared. Models were externally validated using an independent test cohort. RESULTS: A total to 238 fractures (159 acute and 79 chronic) in 122 patients and 58 fractures (39 acute and 19 chronic) in 32 patients were included in the training and test cohorts, respectively. The area under the receiver operating characteristic curve (AUC) of the radiomic score was 0.95 in the training and 0.93 in the test cohorts. The AUC of the radiologic model was 0.89 in the training and 0.83 in the test cohorts. The discriminatory performance of the integrated model was significantly higher than the radiologic model in both the training (AUC, 0.97; p<0.01) and the test (AUC, 0.83; p=0.01) cohorts. CONCLUSION: Combining radiomics with radiologic findings significantly improved the performance of CT in determining the acuity of vertebral compression fractures.

18.
J Gastroenterol Hepatol ; 37(2): 319-326, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34562328

RESUMO

BACKGROUND AND AIM: The efficacy and safety of the recently introduced low-volume purgatives in elderly people are not well known. Therefore, in this trial, we aimed to evaluate and compare the efficacy of two low-volume agents, oral sulfate solution (OSS) and 2-L polyethylene glycol with ascorbic acid (PEG-Asc), in elderly people. METHODS: A prospective, randomized, single-blinded, multicenter, non-inferiority trial was performed at three university-affiliated hospitals in South Korea. Outpatients aged 65-80 years, who underwent elective colonoscopy, were enrolled. The primary outcome was the rate of adequate bowel preparation assessed using the Boston Bowel Preparation Scale. RESULTS: A total of 199 subjects were randomized into the OSS (n = 99) or the 2-L PEG-Asc (n = 100) group. Of them, 189 subjects were included in the analysis of the primary outcome (OSS group 95 vs PEG-Asc group 94). The proportion of adequate bowel preparation was 89.5% (85/95) in the OSS group and 93.6% (88/94) in the 2-L PEG-Asc group. OSS was not inferior to 2-L PEG-Asc according to the prespecified non-inferiority margin of -15% (95% confidence interval for the difference, -12.1 to 3.8). Vomiting (11.6% vs 2.1%) and thirst (24.2% vs 11.7%) were more common in the OSS group than in the 2-L PEG-Asc group. CONCLUSIONS: OSS is an effective low-volume purgative that is non-inferior to 2-L PEG-Asc in elderly people. Both the low-volume agents were identified to be well tolerated and safe in the healthy elderly population.


Assuntos
Ácido Ascórbico , Catárticos , Polietilenoglicóis , Sulfatos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , Catárticos/administração & dosagem , Catárticos/efeitos adversos , Colonoscopia , Humanos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , Sulfatos/administração & dosagem , Sulfatos/efeitos adversos , Resultado do Tratamento
19.
Biochem Biophys Res Commun ; 586: 171-176, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34856417

RESUMO

High temperature stress is an environmental factor that negatively affects the growth and development of crops. Hsp90 (90 kDa heat shock protein) is a major molecular chaperone in eukaryotic cells, contributing to the maintenance of cell homeostasis through interaction with co-chaperones. Aha1 (activator of Hsp90 ATPase) is well known as a co-chaperone that activates ATPase activity of Hsp90 in mammals. However, biochemical and physiological evidence relating to Aha has not yet been identified in plants. In this study, we investigated the heat-tolerance function of orchardgrass (Dactylis glomerata L.) Aha (DgAha). Recombinant DgAha interacted with cytosolic DgHsp90s and efficiently protected substrates from thermal denaturation. Furthermore, heterologous expression of DgAha in yeast (Saccharomyces cerevisiae) cells and Arabidopsis (Arabidopsis thaliana) plants conferred thermotolerance in vivo. Enhanced expression of DgAha in Arabidopsis stimulates the transcription of Hsp90 under heat stress. Our data demonstrate that plant Aha plays a positive role in heat stress tolerance via chaperone properties and/or activation of Hsp90 to protect substrate proteins in plants from thermal injury.


Assuntos
Proteínas de Arabidopsis/genética , Dactylis/genética , Proteínas de Choque Térmico HSP90/genética , ATPases Translocadoras de Prótons/genética , Termotolerância/genética , Transcrição Genética , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Dactylis/metabolismo , Regulação da Expressão Gênica de Plantas , Teste de Complementação Genética , Proteínas de Choque Térmico HSP90/metabolismo , Temperatura Alta , Cinética , Ligação Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Estresse Fisiológico
20.
Food Chem ; 374: 131493, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-34802809

RESUMO

Soy isoflavones (SIs) show various health benefits, such as antioxidant and estrogenic effects. It is important to understand the bioaccessibility and bioavailability of SIs due to the close relation to their bioactivities. In this study, the antioxidant capacity, bioaccessibility, and bioavailability of 12 SIs were evaluated using radical-scavenging methods, simulations of human digestion, and Caco-2 cells in Transwell, respectively. All SIs were stable (91.1-99.2%) under gastric digestion conditions compared with the control (100%), whereas acetyl and malonyl conjugates were unstable (38.5% and 65.5%, respectively) under small intestinal digestion conditions. SI aglycones showed higher permeability (7-15 times) and cellular accumulation (8.8 times) than their glucosides. A small amount of SI conjugates was intact in the cell and in the basolateral side of each Transwell. These results suggest that SI conjugates, especially malonyl and acetyl forms, have incidental bioactivity after being metabolized to aglycones inside the cell.


Assuntos
Isoflavonas , Soja , Antioxidantes , Disponibilidade Biológica , Células CACO-2 , Digestão , Humanos
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