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2.
Issues Ment Health Nurs ; : 1-10, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286089

RESUMO

Purpose: The purpose of this paper is to provide readers with a comprehensive overview of scholarly work on the depression of caregivers using bibliometrics and text mining. Methods: A total of 426 articles published between 2000 and 2018 were retrieved from the Clarivate Analytics Web of Science, and then, computer-aided bibliometric analysis as well as Latent Dirichlet Allocation (LDA) topic modeling were conducted on the collection of the data. Results: Descriptive statistics on the increasing number of publications, network analysis of scientific collaboration between countries, word co-occurrence analysis, conceptual structure, and six latent topics (k = 6) identified are discussed. Conclusions: Preventing or managing depression among caregivers is a growing field with the highest priority for the aging population. In the future, collaborating between countries and reflecting cultural backgrounds in caregiver depression research are needed. This study is expected to contribute to the field of psychological distress of caregivers in looking a big picture of the current position through data-driven analysis and moving forward towards a better direction.

3.
J Craniomaxillofac Surg ; 48(4): 427-434, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32192906

RESUMO

PURPOSE: The purpose of this study was to investigate concomitant injuries and complications in patients with panfacial fracture (PF) according to patterns of PF. MATERIALS AND METHODS: PF is defined as fractures involving at least three of the four facial parts (frontal, upper midface, lower midface, and mandible). The data for this study were retrospectively analysed. A simple regression analysis, Cramer's V analysis, and Pearson's correlation analysis were used for verifying significance and correlation between the investigated factors and patterns of PF. Short-term postoperative surgical complications were classified according to the Clavien-Dindo classification (CDC). RESULTS: There was a statistically significant association between age and PF pattern (ULM: 44.9 ± 19.2; FUL: 42.0 ± 16.8; FULM: 33.6 ± 15.3; FUM: 65; p = 0.024), between the cause of injury and PF pattern (p = 0.047), and between operative time and fracture pattern (ULM: 4h 45min ± 2h 21min; FUL: 5h 19min ± 2h 54min; FULM: 7h 19min ± 4h 13min; FUM: 2h 15min ± 0; p = 0.008). 89% of patients had concomitant injuries in other body parts. In the CDC grade groups, rade IVa cases (n = 4) showed statistically significant differences with PF patterns (p = 0.006). Of all the patients, 58.6% (n = 58) complained of postoperative complications. CONCLUSION: PF patients can have different fracture patterns, depending on age and cause of trauma. Consequently, different PF patterns have different types of concomitant injuries and complications. PF patients with frontal area fracture have higher CDC grades, and may need ICU care. Therefore, classifying PFs will be a first step towards a systemic approach for treating and reducing complications.

5.
J Korean Acad Nurs ; 50(1): 132-146, 2020 Feb.
Artigo em Coreano | MEDLINE | ID: mdl-32131078

RESUMO

PURPOSE: The purpose of this study was to develop a new version of Spirituality Assessment Scale (N-SAS) and verify its reliability and validity. METHODS: The total of 59 preliminary items for the N-SAS were selected through a literature review, two rounds of experts' content validation, cognitive interviews, and pre-tests. Verification of its reliability and validity was divided into two phases. In Phase I, questionnaires were collected from 219 adults. Reliability was tested using Cronbach's alpha, validity with item analysis, and exploratory factor analysis. In Phase II, questionnaires developed based on the results of Phase I were collected from 225 adults. Reliability was tested using Cronbach's alpha, validity with confirmatory factor analysis, and criterion validity. RESULTS: The final version of the N-SAS comprised two dimensions (vertical and horizontal), four domains (relationship with God; meaning of life and self-integration; self-transcendence; and relationship with others, neighborhoods, and nature), and 44 items were identified. Total Cronbach's α was .97; those of each subscale ranged from .79 to .98. N-SAS scores were positively correlated with the scores of Howden's Spiritual Assessment Scale (r=.81, p<.001). CONCLUSION: Findings suggest that the N-SAS can be used to measure spirituality in adults. The use of N-SAS is expected to facilitate perceiving patient's spiritual needs and providing spiritual care.

6.
Med Image Anal ; 61: 101635, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32007699

RESUMO

Characterizing functional brain connectivity using resting functional magnetic resonance imaging (fMRI) is challenging due to the relatively small Blood-Oxygen-Level Dependent contrast and low signal-to-noise ratio. Denoising using surface-based Laplace-Beltrami (LB) or volumetric Gaussian filtering tends to blur boundaries between different functional areas. To overcome this issue, a time-based Non-Local Means (tNLM) filtering method was previously developed to denoise fMRI data while preserving spatial structure. The kernel and parameters that define the tNLM filter need to be optimized for each application. Here we present a novel Global PDF-based tNLM filtering (GPDF) algorithm that uses a data-driven kernel function based on a Bayes factor to optimize filtering for spatial delineation of functional connectivity in resting fMRI data. We demonstrate its performance relative to Gaussian spatial filtering and the original tNLM filtering via simulations. We also compare the effects of GPDF filtering against LB filtering using individual in-vivo resting fMRI datasets. Our results show that LB filtering tends to blur signals across boundaries between adjacent functional regions. In contrast, GPDF filtering enables improved noise reduction without blurring adjacent functional regions. These results indicate that GPDF may be a useful preprocessing tool for analyses of brain connectivity and network topology in individual fMRI recordings.

7.
Am J Pathol ; 190(3): 689-701, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31953039

RESUMO

The incidence of pancreatic neuroendocrine tumor (PNET) is increasing, and it presents with various clinical manifestations and an unfavorable survival rate. A better understanding of the drivers of PNET tumorigenesis is urgently needed. Distinct miRNA signatures have been identified for different stages of tumorigenesis in both human and mouse PNETs. The functions of these miRNAs are poorly understood. miR-431 is the most up-regulated miRNA in the metastatic signature. However, it is unknown whether miR-431 contributes to metastasis of PNETs. Herein, we show that miR-431 overexpression activates Ras/extracellular signal-regulated kinase (Erk) signaling and promotes epithelial-mesenchymal transition, migration/invasion in vitro, and metastasis in both xenograft and spontaneous mouse models of PNET. Treatment of PNET cells with Erk inhibitor or locked nucleic acids sequestering miR-431 inhibits invasion. Four target prediction modules and dual-luciferase reporter assays were used to identify potential mRNA targets of miR-431. A Ras GTPase activating protein tumor suppressor (RasGAP), DAB2 interacting protein (DAB2IP), was discovered as an miR-431 target. Overexpression of DAB2IP's rat homolog, but not its mutant defective in Ras GTPase activating protein activity, reverses miR-431's effect on promoting invasion, Erk phosphorylation, and epithelial-mesenchymal transition of PNETs. Taken together, miR-431 silences DAB2IP to active Ras/Erk and promote metastasis of PNETs. miR-431 may be targeted to manage metastatic PNETs.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas Reguladoras de Apoptose/genética , Carcinogênese , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Metástase Neoplásica , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Ratos , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/metabolismo
8.
Antibodies (Basel) ; 8(3)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31544848

RESUMO

Since its first report in the Middle East in 2012, the Middle East respiratory syndrome-coronavirus (MERS-CoV) has become a global concern due to the high morbidity and mortality of individuals infected with the virus. Although the majority of MERS-CoV cases have been reported in Saudi Arabia, the overall risk in areas outside the Middle East remains significant as inside Saudi Arabia. Additional pandemics of MERS-CoV are expected, and thus novel tools and reagents for therapy and diagnosis are urgently needed. Here, we used phage display to develop novel monoclonal antibodies (mAbs) that target MERS-CoV. A human Fab phage display library was panned against the S2 subunit of the MERS-CoV spike protein (MERS-S2P), yielding three unique Fabs (S2A3, S2A6, and S2D5). The Fabs had moderate apparent affinities (Half maximal effective concentration (EC50 = 123-421 nM) for MERS-S2P, showed no cross-reactivity to spike proteins from other CoVs, and were non-aggregating and thermostable (Tm = 61.5-80.4 °C). Reformatting the Fabs into IgGs (Immunoglobulin Gs) greatly increased their apparent affinities (KD = 0.17-1.2 nM), presumably due to the effects of avidity. These apparent affinities were notably higher than that of a previously reported anti-MERS-CoV S2 reference mAb (KD = 8.7 nM). Furthermore, two of the three mAbs (S2A3 and S2D5) bound only MERS-CoV (Erasmus Medical Center (EMC)) and not other CoVs, reflecting their high binding specificity. However, the mAbs lacked MERS-CoV neutralizing activity. Given their high affinity, specificity, and desirable stabilities, we anticipate that these anti-MERS-CoV mAbs would be suitable reagents for developing antibody-based diagnostics in laboratory or hospital settings for point-of-care testing.

9.
J Exp Clin Cancer Res ; 38(1): 363, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426843

RESUMO

BACKGROUND: In order to develop a new immunotherapeutic agent targeting metastatic breast cancers, we chose to utilize autocatalytic feature of the membrane serine protease Prss14/ST14, a specific prognosis marker for ER negative breast cancer as a target molecule. METHODS: The study was conducted using three mouse breast cancer models, 4 T1 and E0771 mouse breast cancer cells into their syngeneic hosts, and an MMTV-PyMT transgenic mouse strain was used. Prss14/ST14 knockdown cells were used to test function in tumor growth and metastasis, peptides derived from the autocatalytic loop for activation were tested as preventive metastasis vaccine, and monoclonal and humanized antibodies to the same epitope were tested as new therapeutic candidates. ELISA, immunoprecipitation, Immunofluorescent staining, and flow cytometry were used to examine antigen binding. The functions of antibodies were tested in vitro for cell migration and in vivo for tumor growth and metastasis. RESULTS: Prss14/ST14 is critically involved in the metastasis of breast cancer and poor survival rather than primary tumor growth in two mouse models. The epitopes derived from the specific autocatalytic loop region of Prss14/ST14, based on structural modeling acted as efficient preventive metastasis vaccines in mice. A new specific monoclonal antibody mAb3F3 generated against the engineered loop structure could reduce cell migration, eliminate metastasis in PyMT mice, and can detect the Prss14/ST14 protein expressed in various human cancer cells. Humanized antibody huAb3F3 maintained the specificity and reduced the migration of human breast cancer cells in vitro. CONCLUSION: Our study demonstrates that Prss14/ST14 is an important target for modulating metastasis. Our newly developed hybridoma mAbs and humanized antibody can be further developed as new promising candidates for the use in diagnosis and in immunotherapy of human metastatic breast cancer.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais/farmacologia , Neoplasias da Mama/prevenção & controle , Epitopos/imunologia , Neoplasias Pulmonares/prevenção & controle , Fragmentos de Peptídeos/imunologia , Serina Endopeptidases/imunologia , Animais , Antígenos Transformantes de Poliomavirus/genética , Apoptose , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Vírus do Tumor Mamário do Camundongo/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Am Chem Soc ; 141(37): 14673-14686, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31436967

RESUMO

Tumor initiating cells (TIC) are resistant to conventional anticancer therapy and associated with metastasis and relapse in cancer. Although various TIC markers and their antibodies have been proposed, it is limited to the use of antibodies for in vivo imaging or treatment of TIC. In this study, we discovered heme oxygenase 2 (HMOX2) as a novel biomarker for TIC and developed a selective small molecule probe TiNIR (tumor initiating cell probe with near infrared). TiNIR detects and enriches the functionally active TIC in human lung tumors, and through the photoacoustic property, TiNIR also visualizes lung TIC in the patient-derived xenograft (PDX) model. Furthermore, we demonstrate that TiNIR inhibits tumor growth by blocking the function of HMOX2, resulting in significantly increased survival rates of the cancer model mice. The novel therapeutic target HMOX2 and its fluorescent ligand TiNIR will open a new path for the molecular level of lung TIC diagnosis and treatment.

11.
Am J Hematol ; 94(10): 1055-1065, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31259431

RESUMO

Severe chronic anemia is an independent predictor of overt stroke, white matter damage, and cognitive dysfunction in the elderly. Severe anemia also predisposes to white matter strokes in young children, independent of the anemia subtype. We previously demonstrated symmetrically decreased white matter (WM) volumes in patients with sickle cell disease (SCD). In the current study, we investigated whether patients with non-sickle anemia also have lower WM volumes and cognitive dysfunction. Magnetic Resonance Imaging was performed on 52 clinically asymptomatic SCD patients (age = 21.4 ± 7.7; F = 27, M = 25; hemoglobin = 9.6 ± 1.6 g/dL), 26 non-sickle anemic patients (age = 23.9 ± 7.9; F = 14, M = 12; hemoglobin = 10.8 ± 2.5 g/dL) and 40 control subjects (age = 27.7 ± 11.3; F = 28, M = 12; hemoglobin = 13.4 ± 1.3 g/dL). Voxel-wise changes in WM brain volumes were compared to hemoglobin levels to identify brain regions that are vulnerable to anemia. White matter volume was diffusely lower in deep, watershed areas proportionally to anemia severity. After controlling for age, sex, and hemoglobin level, brain volumes were independent of disease. WM volume loss was associated with lower Full Scale Intelligence Quotient (FSIQ; P = .0048; r2 = .18) and an abnormal burden of silent cerebral infarctions (P = .029) in males, but not in females. Hemoglobin count and cognitive measures were similar between subjects with and without white-matter hyperintensities. The spatial distribution of volume loss suggests chronic hypoxic cerebrovascular injury, despite compensatory hyperemia. Neurocognitive consequences of WM volume changes and silent cerebral infarction were strongly sexually dimorphic. Understanding the possible neurological consequences of chronic anemia may help inform our current clinical practices.

12.
Mol Cancer ; 18(1): 92, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31072393

RESUMO

The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers. We previously screened genes upregulated in human hepatocellular carcinomas for their metastatic function in a mouse model of pancreatic neuroendocrine tumor (PNET) and identified that human RHAMMB promoted liver metastasis. It was unknown whether RHAMMB is upregulated in pancreatic cancer or contributes to its progression. In this study, we found that RHAMM protein was frequently upregulated in human PNETs. We investigated alternative splicing isoforms, RHAMMA and RHAMMB, by RNA-Seq analysis of primary PNETs and liver metastases. RHAMMB, but not RHAMMA, was significantly upregulated in liver metastases. RHAMMB was crucial for in vivo metastatic capacity of mouse and human PNETs. RHAMMA, carrying an extra 15-amino acid-stretch, did not promote metastasis in spontaneous and experimental metastasis mouse models. Moreover, RHAMMB was substantially higher than RHAMMA in pancreatic ductal adenocarcinoma (PDAC). RHAMMB, but not RHAMMA, correlated with both higher EGFR expression and poorer survival of PDAC patients. Knockdown of EGFR abolished RHAMMB-driven PNET metastasis. Altogether, our findings suggest a clinically relevant function of RHAMMB, but not RHAMMA, in promoting PNET metastasis in part through EGFR signaling. RHAMMB can thus serve as a prognostic factor for pancreatic cancer.

13.
Angew Chem Int Ed Engl ; 58(25): 8426-8431, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31025486

RESUMO

The rapid and sensitive classification of bacteria is the first step of bacterial community research and the treatment of infection. Herein, a fluorescent probe BacGO is presented, which shows the best universal selectivity for Gram-positive bacteria among known probes with a minimum staining procedure for sample detection and enrichment of the live bacteria. BacGO could also be used to assess of the Gram status in the bacterial community from wastewater sludge. Furthermore, BacGO could sensitively and selectively detect a Gram-positive bacterial infection, not only in vitro but also using an in vivo keratitis mouse model. BacGO provides an unprecedented research tool for the study of dynamic bacterial communities and for clinical application.

14.
BMJ Glob Health ; 4(2): e001133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30997161

RESUMO

Background: Engaging in public health activities in the Democratic People's Republic of Korea (DPRK, also known as North Korea) offers a means to improve population health for its citizens and the wider region. Such an engagement requires an understanding of current and future needs. Methods: We conducted a systematic search of five English and eight Korean language databases to identify available literature published between 1988 and 2017. A narrative review of evidence was conducted for five major categories (health systems, communicable diseases (CDs), non-communicable diseases (NCDs), injuries, and reproductive, maternal, newborn and child health (RMNCH) and nutrition). Findings: We found 465 publications on the DPRK and public health. Of the 253 articles that addressed major disease categories, we found under-representation of publications relative to proportion of disease burden for the two most significant causes: NCDs (54.5% publications vs 72.6% disability adjusted life years (DALYs)) and injuries (0.4% publications vs 12.1% DALYs), in comparison to publications on the third and fourth largest disease burdens, RMNCH and nutrition (30.4% publications vs 8.6% DALYs) and CDs (14.6% publications vs 6.7% DALYs) which were over-represented. Although most disease category articles were on NCDs, the majority of NCD articles addressed mental health of refugees. Only 165 articles addressed populations within the DPRK and among these, we found publication gaps on social and environmental determinants of health, CDs, and NCDs. Conclusion: There are gaps in the public health literature on the DPRK. Future research should focus on under-studied, significant burdens of disease. Moreover, establishing more precise estimates of disease burden and their distribution, as well as analysis on health systems responses aimed at addressing them, can result in improvements in population health.

15.
J Periodontal Res ; 54(5): 533-545, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30982986

RESUMO

OBJECTIVE: We evaluated the role of oleanolic acid acetate (OAA), a triterpenoid commonly used in the treatment of liver disorders, inflammatory diseases, and metastasis, in bone formation after tooth loss by periodontitis. BACKGROUND: Periodontitis causes the sequential degradation of the alveolar bone and associated structures, resulting in tooth loss. Several studies have attempted to regenerate the bone for implantation following tooth loss. METHODS: Maxillary left second molar was extracted from 8-week-old male mice following induction of periodontitis by ligature for 5 days. The extraction socket was treated with 50 ng/µL OAA for 1, 2, and 3 weeks. Detailed morphological changes were examined using Masson's trichrome staining, and the precise localization patterns of various signaling molecules, including CD31, F4/80, interleukin (IL)-6, and osteocalcin, were observed. The volume of bone formation was examined by Micro-CT. Osteoclasts were enumerated using tartrate-resistant acid phosphatase (TRAP) staining. For molecular dissection of signaling molecules, we employed the hanging-drop in vitro cultivation method at E14 for 1 day and examined the expression pattern of transforming growth factor (TGF)-ß superfamily and Wnt signaling genes. RESULTS: Histomorphometrical examinations showed facilitated bone formation in the extraction socket following OAA treatment. In addition, OAA-treated specimens showed the altered localization patterns of inflammatory and bone formation-related signaling molecules including CD31, F4/80, IL-6, and osteocalcin. Also, embryonic tooth germ mesenchymal tissue cultivation with OAA treatment showed the significant altered expression patterns of signaling molecules such as transforming growth factor (TGF)-ß superfamily and Wnt signaling. CONCLUSIONS: Oleanolic acid acetate induces bone formation and remodeling through proper modulation of osteoblast, osteoclast, and inflammation with regulations of TGF-ß and Wnt signaling.


Assuntos
Perda do Osso Alveolar , Ácido Oleanólico , Osteogênese , Periodontite , Acetatos , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Ácido Oleanólico/farmacologia , Osteoclastos
16.
Cancers (Basel) ; 11(3)2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893927

RESUMO

Cancer-associated fibroblast (CAF)-specific proteins serve as both prognostic biomarkers and targets for anticancer drugs. In this study, we investigated the role of NGFI-A-binding protein (NAB)2 derived from CAFs in the progression of head and neck squamous cell carcinoma (HNSCC). Patient-derived HNSCC and paired metastatic lymph node tissues were examined for NAB2 expression by immunohistochemistry. Primary CAF cultures were established from HNSCC patient tissue, with paired non-tumor fibroblasts (NTFs) serving as a control. CAF or NTF was used to evaluate the effect of NAB2 on HNSCC progression using FaDu cell spheroids and an in vivo mouse xenograft model. NAB2 was detected in interstitial CAFs in primary and metastatic lymph node tissues of HNSCC patients. NAB2 mRNA and protein levels were higher in CAFs as compared to paired NTFs. Conditioned medium (CM) of NAB2-overexpressing CAFs increased the invasion of FaDu spheroids in the Matrigel invasion assay as compared to CM of NTF. Co-injection of NAB2-overexpressing CAFs with FaDu spheroids into mice enhanced the growth of tumors. These data suggest that NAB2-overexpressing CAFs promotes HNSCC progression and is a potential therapeutic target for preventing HNSCC metastasis.

17.
Nurs Forum ; 54(2): 280-290, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30737798

RESUMO

The inclusion of caregivers in a holistic care approach represents a basic principle in palliative care. However, many palliative care professionals have a lack of understanding of difficulties or unmet needs among caregivers. To enhance the quality of life of caregivers and the quality of care for patients, healthcare professionals should be better informed about the constructs of caregiver burden. The aim of this study is to synthesize the concept of caregiver burden in palliative care, providing implications for the caregivers and their support systems. This concept analysis study adopts the integrative review approach and the basic text analysis method (ie, word frequency). The PubMed, CINAHL, Embase, and PsycINFO databases are explored for eligible studies. From this literature search, 66 articles from 1998 to 2018 are located. After data collection is completed, the two authors independently evaluate the quality of studies published before 1 September 2018. The caregiver burden is then redefined with its attributes, antecedents, consequences, empirical referents, and facilitators. It is recommended that the multidimensional concept of caregiver burden in palliative care be measured by considering caregiver characteristics and the caregiving context.


Assuntos
Cuidadores/psicologia , Cuidados Paliativos/métodos , Qualidade de Vida , Adaptação Psicológica , Idoso , Idoso de 80 Anos ou mais , Cuidadores/economia , Formação de Conceito , Mineração de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/economia , Cuidados Paliativos/psicologia
18.
J Prosthet Dent ; 121(2): 225-228, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30722984

RESUMO

Tuberculosis (TB) of the oral cavity may be overlooked in the differential diagnosis of oral lesions and can be misdiagnosed and managed incorrectly. A 66-year-old man with complete dentures presented with a nonhealing mucosal ulcer in the upper lip. Despite the treatments performed by a local medical clinic, the ulcerative lesion on the denture-bearing area had not improved over 5 months. A partial excisional biopsy was performed to investigate further. Histopathologic examination revealed granulomatous inflammation caused by TB, and a chest radiograph showed consolidation and cavitation of the upper lobes. The patient was diagnosed with pulmonary TB. This clinical report describes the management of oral TB mimicking a traumatic denture ulcer in a patient with long-term complete denture use.


Assuntos
Úlceras Orais , Tuberculose Bucal , Idoso , Prótese Total , Humanos , Masculino , Mucosa Bucal , Úlcera
19.
Am J Hematol ; 94(4): 467-474, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30697803

RESUMO

Although modern medical management has lowered overt stroke occurrence in patients with sickle cell disease (SCD), progressive white matter (WM) damage remains common. It is known that cerebral blood flow (CBF) increases to compensate for anemia, but sufficiency of cerebral oxygen delivery, especially in the WM, has not been systematically investigated. Cerebral perfusion was measured by arterial spin labeling in 32 SCD patients (age range: 10-42 years old, 14 males, 7 with HbSC, 25 HbSS) and 25 age and race-matched healthy controls (age range: 15-45 years old, 10 males, 12 with HbAS, 13 HbAA); 8/24 SCD patients were receiving regular blood transfusions and 14/24 non-transfused SCD patients were taking hydroxyurea. Imaging data from control subjects were used to calculate maps for CBF and oxygen delivery in SCD patients and their T-score maps. Whole brain CBF was increased in SCD patients with a mean T-score of 0.5 and correlated with lactate dehydrogenase (r2 = 0.58, P < 0.0001). When corrected for oxygen content and arterial saturation, whole brain and gray matter (GM) oxygen delivery were normal in SCD, but WM oxygen delivery was 35% lower than in controls. Age and hematocrit were the strongest predictors for WM CBF and oxygen delivery in patients with SCD. There was spatial co-localization between regions of low oxygen delivery and WM hyperintensities on T2 FLAIR imaging. To conclude, oxygen delivery is preserved in the GM of SCD patients, but is decreased throughout the WM, particularly in areas prone to WM silent strokes.


Assuntos
Anemia Falciforme , Circulação Cerebrovascular , Angiografia por Ressonância Magnética , Oxigênio/metabolismo , Substância Branca , Adolescente , Adulto , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/metabolismo , Anemia Falciforme/fisiopatologia , Feminino , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/irrigação sanguínea , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Substância Branca/fisiopatologia
20.
J Periodontol ; 90(5): 546-554, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30387495

RESUMO

BACKGROUND: Periodontitis is not only one of the most prevalent inflammatory diseases among adults, but also commonly linked to numerous systemic conditions including cardiovascular diseases, stroke, and diabetes. Although osteoclasts are responsible for the alveolar bone resorption during periodontitis pathogenesis, the development of pharmacologic strategies targeting these cells has not been vastly fruitful. METHODS: Bone marrow macrophages were cultured in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL) to examine the direct effect of acalabrutinib on osteoclastogenesis. Ca2+ oscillation and nuclear localization of NFATc1 in osteoclast precursors were examined to determine the precise molecular mechanism. LPS-induced alveolar bone loss model was employed for studying effect in in vivo bone resorption. RESULTS: Acalabrutinib directly inhibited RANKL and LPS-induced in vitro osteoclast differentiation. In addition, acalabrutinib inhibited RANKL-induced phosphorylation of mitogen-activated protein kinases and reduced the expression of NF-κB. The inhibitory mechanism involved suppression of Ca2+ oscillation in osteoclast precursors resulting in the decreased NFATc1 expression and nuclear localization, which is a crucial prerequisite for osteoclastogenesis. The administration of acalabrutinib significantly reduced P. gingivalis lipopolysaccharide-induced alveolar bone erosion in mice. CONCLUSION: These data indicate that acalabrutinib is an effective inhibitor of osteoclastogenesis both in vitro and in vivo, with a potential for a novel strategy against bone destruction by periodontitis.


Assuntos
Perda do Osso Alveolar , Reabsorção Óssea , Tirosina Quinase da Agamaglobulinemia , Animais , Benzamidas , Células da Medula Óssea , Diferenciação Celular , Lipopolissacarídeos , Camundongos , Fatores de Transcrição NFATC , Osteoclastos , Porphyromonas gingivalis , Pirazinas , Ligante RANK
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