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INTRODUCTION: Posttraumatic stress disorder (PTSD) results in substantial costs to society. Prevalence of PTSD among adults is high, especially among those presenting to primary care settings. Evidence-based psychotherapies (EBPs) for PTSD are available but dissemination and implementation within primary care settings is challenging. Building Experience for Treating Trauma and Enhancing Resilience (BETTER) examines the effectiveness of integrating Written Exposure Therapy (WET) within primary care collaborative care management (CoCM). WET is a brief exposure-based treatment that has the potential to address many challenges of delivering PTSD EBPs within primary care settings. METHODS: The study is a hybrid implementation effectiveness cluster-randomized controlled trial in which 12 Federally Qualified Health Centers (FQHCs) will be randomized to either CoCM plus WET (CoCM+WET) or CoCM only with 60 patients within each FQHC. The primary aim is to evaluate the effectiveness of CoCM+WET to improve PTSD and depression symptom severity. Secondary treatment outcomes are mental and physical health functioning. The second study aim is to examine implementation of WET within FQHCs using FQHC process data and staff interviews pre- and post-intervention. Exploratory aims are to examine potential moderators and mediators of the intervention. Assessments occur at baseline, and 3- and 12-month follow-up. CONCLUSION: The study has the potential to impact practice and improve clinical and public health outcomes. By establishing the effectiveness and feasibility of delivering a brief trauma-focused EBP embedded within CoCM in primary care, the study aims to improve PTSD outcomes for underserved patients. TRIAL REGISTRATION: (Clinicaltrials.govNCT05330442).
Subject(s)
Implosive Therapy , Stress Disorders, Post-Traumatic , Adult , Humans , Stress Disorders, Post-Traumatic/therapy , Treatment Outcome , Crisis Intervention , Primary Health CareABSTRACT
(1) Background: With increasing international travel and mass population displacement due to war, famine, climate change, and immigration, pathogens, such as Staphylococcus aureus (S. aureus), can also spread across borders. Methicillin-resistant S. aureus (MRSA) most commonly causes skin and soft tissue infections (SSTIs), as well as more invasive infections. One clonal strain, S. aureus USA300, originating in the United States, has spread worldwide. We hypothesized that S. aureus USA300 would still be the leading clonal strain among US-born compared to non-US-born residents, even though risk factors for SSTIs may be similar in these two populations (2) Methods: In this study, 421 participants presenting with SSTIs were enrolled from six community health centers (CHCs) in New York City. The prevalence, risk factors, and molecular characteristics for MRSA and specifically clonal strain USA300 were examined in relation to the patients' self-identified country of birth. (3) Results: Patients born in the US were more likely to have S. aureus SSTIs identified as MRSA USA300. While being male and sharing hygiene products with others were also significant risks for MRSA SSTI, we found exposure to animals, such as owning a pet or working at an animal facility, was specifically associated with risk for SSTIs caused by MRSA USA300. Latin American USA300 variant (LV USA300) was most common in participants born in Latin America. Spatial analysis showed that MRSA USA300 SSTI cases were more clustered together compared to other clonal types either from MRSA or methicillin-sensitive S. aureus (MSSA) SSTI cases. (4) Conclusions: Immigrants with S. aureus infections have unique risk factors and S. aureus molecular characteristics that may differ from US-born patients. Hence, it is important to identify birthplace in MRSA surveillance and monitoring. Spatial analysis may also capture additional information for surveillance that other methods do not.
ABSTRACT
Low-income women of color receive fewer cancer screenings and have higher rates of depression, which can interfere with cancer screening participation. This study assessed the comparative effectiveness of two interventions for improving colorectal, breast, and cervical cancer screening participation and reducing depression among underserved women in Bronx, NY, with depression. This comparative effectiveness randomized controlled trial (RCT) with assessments at study entry, 6, and 12 months utilized an intent-to-treat statistical approach. Eligible women were aged 50 to 64, screened positive for depression, and were overdue for ≥ 1 cancer screening (colorectal, breast, and/or cervical). Participants were randomized to a collaborative depression care plus cancer screening intervention (CCI + PCM) or cancer screening intervention alone (PCM). Interventions were telephone-based, available in English or Spanish, delivered over 12 months, and facilitated by a skilled care manager. Cancer screening data were extracted from electronic health records. Depression was measured with a validated self-report instrument (PHQ-9). Seven hundred fifty seven women consented and were randomized (CCI + PCM, n = 378; PCM, n = 379). Analyses revealed statistically significant increases in up-to-date status for all three cancer screenings; depression improved in both intervention groups. There were no statistically significant differences between the interventions in improving cancer screening rates or reducing depression. CCI and PCM both improved breast, cervical, and colorectal cancer screening and depression in clinical settings in underserved communities; however, neither intervention showed an advantage in outcomes. Decisions about which approach to implement may depend on the nature of the practice and alignment of the interventions with other ongoing priorities and resources.
ABSTRACT
BACKGROUND: Low-income and minority women are significantly more likely to be diagnosed with preventable, late-stage cancers and suffer from depression than the general population. Intervention studies aiming to reduce depression to increase cancer screening among underserved minority women are sparse. METHODS: This patient-centered outcomes trial compared Collaborative Care Intervention plus Cancer Prevention Care Management (CCI+PCM) versus PCM alone. Participants from six Federally Qualified Health Centers (FQHCs) were interviewed at baseline, 6-and 12-month follow-up to monitor adherence to screening guidelines, depressive symptoms, quality of life, barriers to screening, and other psychosocial and health-related variables. RESULTS: Participants included 757 English-or Spanish-speaking women (ages 50-64) who screened positive for depression on the Patient Health Questionnaire (PHQ)-9 and were not up-to-date for breast, cervical, and/or colorectal cancer screening. CONCLUSIONS: Study methodology and baseline participant characteristics are reported to contribute to the literature on evidence-based interventions for cancer screening among underserved, depressed women.
Subject(s)
Mental Health Services , Neoplasms , Depression/diagnosis , Early Detection of Cancer , Female , Humans , Middle Aged , Neoplasms/diagnosis , Patient-Centered Care , Primary Health Care , Quality of LifeABSTRACT
Objective: To summarize the preliminary experience in the treatment of esthesioneuroblastoma (ENB) and to explore the effect of age, chemotherapy, modified Kadish stage and pathological grade on the prognosis of ENB. Methods: The clinical data of 87 ENB patients from the First Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University Cancer Center between June 2002 and November 2017 were retrospectively analyzed. The modified Kadish stage was used to evaluate the extent of the lesions, and the Hyams grading system was used for pathological grading. The patients were followed up regularly to evaluate the recurrence and metastasis of the tumor. Cox proportional hazard model was used for univariate and multivariate analyses. Prognostic factors with P<0.05 in univariate analysis were included in multivariate analysis. After controlling the confounding factors, the model coefficients were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: The median follow-up time of ENB patients was 29 months, and the 5-year overall survival rate was 39.3%. In univariate analysis, age, chemotherapy, modified Kadish stage and pathology grade were independent predictors of overall survival, while gender, radiotherapy and surgery were not prognostic factors. Multivariate analysis showed that modified Kadish stage and pathology grade were independent predictors of overall survival rate after excluding confounding factors. Conclusions: Age, chemotherapy, modified Kadish stage and pathological grade are taking important role in the overall survival rate of patients with ENB. Modified Kadish stage and pathological grade are independent predictors of overall survival rate.
Subject(s)
Esthesioneuroblastoma, Olfactory , Nose Neoplasms , Esthesioneuroblastoma, Olfactory/pathology , Esthesioneuroblastoma, Olfactory/therapy , Humans , Nasal Cavity/pathology , Neoplasm Recurrence, Local , Neoplasm Staging , Nose Neoplasms/pathology , Nose Neoplasms/therapy , Prognosis , Retrospective StudiesABSTRACT
Objective:Esthesioneuroblastoma(ENB) is a sinonasal rare tumor, and the assessment on the prognosis have not been used with on consensus, our study aims to set an accuracy indicator to predict the outcomes of ENB.Method:A retrospective review was performed on 31 ENB patients. We collected 31 patients with ENB and reviewed the clinical data and pathological slides; modified Kadish stages were evaluated by otolaryngologist and imaging specialist; Hyams grading system were confirmed by two pathologists, who reviewed and paid attention to the pathological characteristics of Hyams grading system. Finally, the relation among the clinical data, pathological features and clinical outcome of these 31 ENB were analyzed by Kaplan-Meier method.Result: The Hyams grading system and modified Kadish stage were considered together seemed to evaluate the prognosis of ENB more accurately, when the scores over 6 points, the patients had the poor prognosis with the mean median survival months of 24.67±32.22, compared with the scores under 6 and the final scores reached at 4, 5, 6, 7, 8, the tumor metastasis rates were 14.3%, 16.7%, 33.3%, 50.0%, 100.0% respectively.Conclusion:Taking the Hyams grading system and modified Kadish stage into consideration, which may evaluate the prognosis of ENB more accurately.
Subject(s)
Esthesioneuroblastoma, Olfactory/diagnosis , Nasal Cavity/pathology , Nose Neoplasms/diagnosis , Esthesioneuroblastoma, Olfactory/pathology , Humans , Neoplasm Grading , Neoplasm Staging , Nose Neoplasms/pathology , Retrospective StudiesABSTRACT
Rock and fluid samples were collected from three hydrothermal chimneys at the Endeavour Segment, Juan de Fuca Ridge to evaluate linkages among mineralogy, fluid chemistry, and microbial community composition within the chimneys. Mössbauer, midinfrared thermal emission, and visible-near infrared spectroscopies were utilized for the first time to characterize vent mineralogy, in addition to thin-section petrography, X-ray diffraction, and elemental analyses. A 282°C venting chimney from the Bastille edifice was composed primarily of sulfide minerals such as chalcopyrite, marcasite, and sphalerite. In contrast, samples from a 300°C venting chimney from the Dante edifice and a 321°C venting chimney from the Hot Harold edifice contained a high abundance of the sulfate mineral anhydrite. Geochemical modeling of mixed vent fluids suggested the oxic-anoxic transition zone was above 100°C at all three vents, and that the thermodynamic energy available for autotrophic microbial redox reactions favored aerobic sulfide and methane oxidation. As predicted, microbes within the Dante and Hot Harold chimneys were most closely related to mesophilic and thermophilic aerobes of the Betaproteobacteria and Gammaproteobacteria and sulfide-oxidizing autotrophic Epsilonproteobacteria. However, most of the microbes within the Bastille chimney were most closely related to mesophilic and thermophilic anaerobes of the Deltaproteobacteria, especially sulfate reducers, and anaerobic hyperthermophilic archaea. The predominance of anaerobes in the Bastille chimney indicated that other environmental factors promote anoxic conditions. Possibilities include the maturity or fluid flow characteristics of the chimney, abiotic Fe2+ and S2- oxidation in the vent fluids, or O2 depletion by aerobic respiration on the chimney outer wall.
ABSTRACT
Respiratory tract infection with Pseudomonas aeruginosa is a major cause of hospital—acquired pneumonia in immune—compromised individuals. Lung infection with P. aeruginosa is often associated with production of various inflammatory cytokines including IL—1β. Production of IL—1β requires proteolytic cleavage by a multiprotein complex termed inflammasome. AIM2 inflammasome recognizes foreign cytosolic double stranded DNA. A role of AIM2 in P. aeruginosa infection has not been reported previously. In this study, we found that P. aeruginosa infection induced degradation of AIM2 protein in macrophages and induction of AIM2 mRNA expression in macrophages and in the lung of mice. Interestingly, P. aeruginosa infection induced a similar level of IL—1β, IL—6 and TNF production in wild—type and AIM2—deficient mice. Similarly, no significant differences in bacterial clearance, neutrophil infiltration and NF—κB activation were observed between wild—type and AIM2—deficient mice following P. aeruginosa lung infection. Our data suggest that AIM2 inflammasome is dispensable for the host defense against P. aeruginosa infection.
Subject(s)
DNA-Binding Proteins/metabolism , Pseudomonas Infections/pathology , Animals , Caspase 1/metabolism , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/genetics , Female , Inflammasomes/metabolism , Interleukin-1beta/analysis , Interleukin-1beta/metabolism , Interleukin-6/analysis , Lung/metabolism , Lung/pathology , Macrophages/immunology , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/metabolism , Neutrophil Infiltration/physiology , Pseudomonas Infections/metabolism , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/pathogenicity , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/analysisABSTRACT
PURPOSE: MicroRNA 34a (miR-34a) is involved in regulating tissue senescence. However, the role of miR-34a in age-related cataracts is unclear. In this study, we evaluated the correlations among the severity of lens opacity, patient age, and miR-34a expression level in the lens epithelium of age-related cataracts for clarifying the role of miR-34a in the lens senescence. METHODS: This study was carried as a case control study in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan. We recorded age of each patient at the time of their cataract surgery and information regarding lens opacity according to a modified version of the Lens Opacities Classification System III. Correlations among age, lens opacity, and miR-34a expression levels were evaluated. RESULTS: This study evaluated 110 patients with a mean age of 73.19 years (SD±10.2). Older patients had higher nuclear cataract (NC), cortical (C), and posterior subcapsular cataract (P) scores (one-way analysis of variance (ANOVA), P<0.05). miR-34a expression levels were significantly different between each age group (ANOVA post hoc Bonferroni's test, P<0.001), and there were moderate correlations between high NC, C, and P cataract scores and high miR-34a levels (Pearson correlation coefficient; R=0.606, 0.575, and 0.515, respectively). CONCLUSIONS: The current study demonstrated positive correlations between high miR-34a levels and high lens opacity severity in NC, C, or P cataracts. These results suggest that miR-34a expression has a role in lens senescence.
Subject(s)
Cataract/metabolism , Lens, Crystalline/metabolism , MicroRNAs/analysis , Aged , Aged, 80 and over , Analysis of Variance , Case-Control Studies , Cataract/pathology , Cohort Studies , Epithelium/metabolism , Female , Humans , Male , Middle Aged , Severity of Illness Index , TaiwanABSTRACT
In G-CSF-mobilized hematopoietic SCT (HSCT), natural killer (NK) cells have a critical role in GVHD and GVL effects. However, regulation of NK cell response to G-CSF remains unclear. This study assayed G-CSF effects in both HSCT donors and NK-92MI cells. The donors who received G-CSF had significantly decreased NK cell cytotoxicity. Levels of phosphatidylinositol 3-kinase (PI3K) and phosphorylated (p)-Akt, but not mammalian target of rapamycin (mTOR), were downregulated in NK cells from G-CSF-injected donors. G-CSF also decreased cytotoxicity without affecting viability and NF-κB of NK-92MI cells. PI3K and p-ERK expression were also decreased in G-CSF-treated NK-92MI cells, and their inhibitors, wortmannin and PD98059, respectively, both enhanced the downregulation of cytotoxicity. These effects were accompanied by decreased expression of a cytotoxicity-related gene, triosephosphate isomerase (TPI). Wortmannin, but not PD98059, enhanced the downregulation of TPI in G-CSF-treated NK-92MI cells, indicating a correlation between PI3K and TPI. We conclude that G-CSF-impaired NK cell cytotoxicity may accompany PI3K/Akt signaling. The effect is transient and NK cells may recover after G-CSF clearance, suggesting that G-CSF-mobilized HSCT may benefit both acute GVHD prevention and late-phase GVL promotion in HSCT recipients.
Subject(s)
Down-Regulation/drug effects , Granulocyte Colony-Stimulating Factor/pharmacology , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation , Immunity, Cellular/drug effects , Killer Cells, Natural/immunology , Peripheral Blood Stem Cell Transplantation , Adult , Androstadienes/pharmacology , Down-Regulation/immunology , Extracellular Signal-Regulated MAP Kinases/immunology , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Flavonoids/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/immunology , Graft vs Host Disease/immunology , Graft vs Host Disease/prevention & control , Graft vs Leukemia Effect/drug effects , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , K562 Cells , Killer Cells, Natural/metabolism , Male , Phosphatidylinositol 3-Kinases/immunology , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation/immunology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/immunology , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/immunology , TOR Serine-Threonine Kinases/metabolism , Tissue Donors , Triose-Phosphate Isomerase/biosynthesis , Triose-Phosphate Isomerase/immunology , WortmanninABSTRACT
AIMS/HYPOTHESIS: The TGF-ß/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways have been shown to play a critical role in the development of renal fibrosis and inflammation in diabetic nephropathy. We therefore examined whether targeting these pathways by a kidney-targeting Smad7 gene transfer has therapeutic effects on renal lesions in the db/db mouse model of type 2 diabetes. METHODS: We delivered Smad7 plasmids into the kidney of db/db mice using kidney-targeting, ultrasound-mediated, microbubble-inducible gene transfer. The histopathology, ultrastructural pathology and pathways of TGF-ß/SMAD2/3-mediated fibrosis and NF-κB-dependent inflammation were evaluated. RESULTS: In this mouse model of type 2 diabetes, Smad7 gene therapy significantly inhibited diabetic kidney injury, compared with mice treated with empty vectors. Symptoms inhibited included: (1) proteinuria and renal function impairment; (2) renal fibrosis such as glomerular sclerosis, tubulo-interstitial collagen matrix abundance and renal inflammation, including Inos (also known as Nos2), Il1b and Mcp1 (also known as Ccl2) upregulation, as well as macrophage infiltration; and (3) podocyte and endothelial cell injury as demonstrated by immunohistochemistry and/or electron microscopy. Further study demonstrated that the improvement of type 2 diabetic kidney injury by overexpression of Smad7 was associated with significantly inhibited local activation of the TGF-ß/SMAD and NF-κB signalling pathways in the kidney. CONCLUSIONS/INTERPRETATION: Our results clearly demonstrate that kidney-targeting Smad7 gene transfer may be an effective therapy for type 2 diabetic nephropathy, acting via simultaneous modulation of the TGF-ß/SMAD and NF-κB signalling pathways.
Subject(s)
Diabetic Nephropathies/metabolism , NF-kappa B/metabolism , Signal Transduction , Smad Proteins/metabolism , Smad7 Protein/metabolism , Transforming Growth Factor beta/metabolism , Animals , Apoptosis , Diabetes Complications/metabolism , Diabetes Mellitus, Type 2/blood , Gene Transfer Techniques , Immunohistochemistry/methods , Male , Mice , Mice, Inbred C57BL , Microscopy, Confocal/methods , Podocytes/metabolism , Polymerase Chain Reaction/methods , UltrasonicsABSTRACT
BACKGROUND: Whether environmental exposures may modulate the effect of the skin barrier gene on atopic dermatitis (AD) remains to be elucidated. OBJECTIVES: To determine whether filaggrin (FLG) variants can serve as a predictor for atopic disorders in Chinese individuals and if allergen exposures may modify the effect of FLG variants on AD by total IgE levels. METHODS: In total, 116 children aged 2-5years with AD and 212 control subjects were analysed for the FLG variants using DNA sequencing. Multiple logistic regression models were performed to estimate the association among FLG polymorphisms and atopic phenotypes. Serum total IgE level, standing for the degree of allergen exposures, was later stratified to determine the effects of FLG polymorphisms on AD. RESULTS: A significant difference in genotype frequency was found among AD cases and controls in FLG P478S polymorphism. FLG P478S GG genotype significantly increased the risk of AD [odds ratio (OR) 4·60, 95% confidence interval (CI) 1·88-11·24]. In addition, among subjects with AD, GG genotypes also significantly increased the risk of developing asthma (OR 4·68, 95% CI 1·37-16·03). Further, a similar result was obtained for allergic rhinitis (OR 3·23, 95% CI 1·01-10·30). Interestingly, the P478S GG genotype was significantly related to AD (OR 5·67, 95% CI 1·93-16·60) in children with IgE level ≥100 kU L(-1) . However, the association was not evident when IgE level was < 100 kU L(-1) . CONCLUSIONS: Our results suggest that the FLG P478S polymorphism may confer susceptibility to the development of AD among Chinese individuals and may be modified by IgE levels.
Subject(s)
Dermatitis, Atopic/blood , Dermatitis, Atopic/genetics , Genetic Predisposition to Disease , Immunoglobulin G/blood , Intermediate Filament Proteins/genetics , Polymorphism, Genetic/genetics , Child, Preschool , Dermatitis, Atopic/diagnosis , Female , Filaggrin Proteins , Gene Frequency , Genetic Markers , Humans , Logistic Models , Male , Phenotype , Sequence Analysis, DNAABSTRACT
BACKGROUND: Little is known about the exposure profiles of melamine in children. We evaluated the association of clinical findings, exposure patterns and biomarkers with nephrolithiasis in children with potential exposure to melamine. METHODS: A case-control study was conducted in children aged 0-16 years with potential exposure to contaminated dairy products. Cases were defined as nephrolithiasis detected by renal ultrasonography. On the basis of different brands of contaminated dairy products consumed, subjects were classified into high exposure, low exposure and control groups with estimated melamine exposure levels of higher than 2.5 ppm, 0.05-2.5 ppm and lower than detection limits <0.05 ppm. We measured urine melamine for those with nephrolithiasis and age-matched and gender-matched controls within the subset of the study population. RESULTS: The duration of consumption of contaminated products was longer in children with nephrolithiasis in the high exposure group than in controls (median (IQR) 12.0 (3.3-24.0) vs 6.0 (4.0-7.0) months; p = 0.048). High melamine exposure levels were significantly associated with nephrolithiasis (OR 61.04 (95% CI 12.73 to 292.84)). The risk was found to increase with estimate melamine exposure levels (p for trend <0.001). Two among 10 affected subjects with nephrolithiasis showed elevated urine melamine levels. In comparison, levels of all 20 controls were lower than the detection limit. CONCLUSIONS: The risk of melamine-associated nephrolithiasis was related to duration of consumption of contaminated products and estimated melamine exposure levels. Though urine melamine was not a sensitive test, it might serve as an exposure biomarker in melamine-associated nephrolithiasis.
Subject(s)
Dairy Products/analysis , Food Contamination , Nephrolithiasis/chemically induced , Triazines/urine , Adolescent , Biomarkers/urine , Case-Control Studies , Child , Child, Preschool , China , Female , Humans , Infant , Infant Formula , Infant, Newborn , Male , Nephrolithiasis/diagnostic imaging , Nephrolithiasis/epidemiology , Risk Factors , Taiwan/epidemiology , Time Factors , Triazines/adverse effects , UltrasonographyABSTRACT
CyberKnife stereotactic radiosurgery (CKSRS) has been proved effective in treating intra-cranial lesions. To treat acoustic neuroma (AN) patients with or without neurofibromatosis Type 2 (NF2) associations, the functional preservation of hearing, trigeminal nerve, and facial nerve are important. Twenty-one patients were treated with hypofractionated CKSRS. Fourteen non-NF2 and seven NF2 patients were enrolled. Cranial nerve function, audiograms, and magnetic resonance images (MRI) were monitored. Mean follow-up was 15 month. Tumors with volumes ranging from 0.13 to 24.8 cm3 (mean 5.4 cm3) were irradiated with the marginal dose 1800-2000 cGy/3 fractions. Tumors were treated with an 80 to 89% isodose line (mean 83%) and mean 97.9% tumor coverage. Two patients experienced hearing deterioration (16.7%) in the non-NF2 group, and 3 patients (50%) in the NF2 group. No facial or trigeminal dysfunction, brain stem toxicity, or cerebellar edema occurred. Tumor regression was seen in 9 patients (43%) and stable in 12 patients (57%). 100% tumor control rate was achieved. Hypofractionated CKSRS was not only effective in tumor control but also excellent in hearing preservation for non-NF2 AN. But for NF2 patients, although the tumor control was remarkable, hearing preservation was modest as in non-NF2 patients.
Subject(s)
Neurofibromatosis 2/surgery , Neuroma, Acoustic/surgery , Radiosurgery/methods , Adult , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neurofibromatosis 2/complications , Neurofibromatosis 2/pathology , Neuroma, Acoustic/complications , Neuroma, Acoustic/pathology , Peripheral Nerves/physiopathologyABSTRACT
Because MyD88 transduces a core set of Toll-like receptor (TLR)-induced signals, microbial-induced host responses can be divided broadly into the MyD88-dependent and MyD88-independent pathways. A specific pathogen induces a distinct pattern of host response dependent upon the signalling pathways employed. Recently, we demonstrated that a MyD88-dependent pathway is essential for the development of early (4-8 h) host response to Pseudomonas aeruginosa lung infection. Here, we show that the development of a delayed (24-48 h) host response to P. aeruginosa is independent of MyD88. Using MyD88-deficient mice, the production of macrophage inflammatory protein 2, tumour necrosis factor and interleukin 1alpha in the airway was observed following P. aeruginosa lung infection for 24 or 48 h. Moreover, the MyD88-deficient mice recruited sufficient neutrophils in the lung and cleared the bacteria efficiently from the lung after 48 h. Thus, the full development of host responses to P. aeruginosa lung infection involves, in a sequential, stepwise fashion, a MyD88-dependent early response and a MyD88-independent delayed mechanism.
Subject(s)
Myeloid Differentiation Factor 88/immunology , Pseudomonas Infections/immunology , Animals , Bronchoalveolar Lavage Fluid/immunology , Chemotactic Factors/biosynthesis , Chemotaxis, Leukocyte/immunology , Cytokines/metabolism , Female , Inflammation Mediators/metabolism , Lung/immunology , Lung/microbiology , Male , Mice , Mice, Inbred C57BL , Myeloid Differentiation Factor 88/deficiency , Neutrophils/immunology , Peroxidase/biosynthesis , Pseudomonas aeruginosa/isolation & purification , Signal Transduction/immunology , Time Factors , Toll-Like Receptor 2/immunology , Toll-Like Receptor 4/immunologyABSTRACT
An aqueous extract of the edible microalga (CP) (1), has recently been tested for its immunomodulatory effects in a human clinical trial. Here, the CP extract was dialyzed and fractionated using Sephadex G 100 chromatography. The effects of a dialyzed aqueous CP extract, fraction 2 , on mast cell mediator release in vitro and ovalbumin-induced allergic airway inflammation in vivo were examined. In vitro, treatment of mouse bone marrow-derived mast cells with 2 for 18 h significantly inhibited antigen (trinitrophenyl-BSA)-induced IL-5 production. In vivo, treatment of mice with 2 during ovalbumin sensitization and stimulation process significantly reduced eosinophil and neutrophil infiltration in the airways. Moreover, fractions obtained by size exclusion chromatography of 2 inhibited IgE-dependent cytokine GM-CSF production from human cord blood-derived mast cells. Taken together, these results suggest that 2 is composed of biopolymers with anti-allergic potential.
Subject(s)
Chlorella/chemistry , Dietary Supplements , Interleukin-5/biosynthesis , Lung/drug effects , Lung/immunology , Mast Cells/drug effects , Animals , Cells, Cultured , Eosinophils/drug effects , Eosinophils/physiology , Female , Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis , Immunoglobulin E/immunology , Mast Cells/physiology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Neutrophils/drug effects , Neutrophils/physiology , OvalbuminABSTRACT
Tissue restoration is the process whereby multiple damaged cell types are replaced to restore the histoarchitecture and function to the tissue. Several theories have been proposed to explain the phenomenon of tissue restoration in amphibians and in animals belonging to higher orders. These theories include dedifferentiation of damaged tissues, transdifferentiation of lineage-committed progenitor cells, and activation of reserve precursor cells. Studies by Young et al. and others demonstrated that connective tissue compartments throughout postnatal individuals contain reserve precursor cells. Subsequent repetitive single cell-cloning and cell-sorting studies revealed that these reserve precursor cells consisted of multiple populations of cells, including tissue-specific progenitor cells, germ-layer lineage stem cells, and pluripotent stem cells. Tissue-specific progenitor cells display various capacities for differentiation, ranging from unipotency (forming a single cell type) to multipotency (forming multiple cell types). However, all progenitor cells demonstrate a finite life span of 50 to 70 population doublings before programmed cell senescence and cell death occurs. Germ-layer lineage stem cells can form a wider range of cell types than a progenitor cell. An individual germ-layer lineage stem cell can form all cells types within its respective germ-layer lineage (i.e., ectoderm, mesoderm, or endoderm). Pluripotent stem cells can form a wider range of cell types than a single germ-layer lineage stem cell. A single pluripotent stem cell can form cells belonging to all three germ layer lineages. Both germ-layer lineage stem cells and pluripotent stem cells exhibit extended capabilities for self-renewal, far surpassing the limited life span of progenitor cells (50-70 population doublings). The authors propose that the activation of quiescent tissue-specific progenitor cells, germ-layer lineage stem cells, and/or pluripotent stem cells may be a potential explanation, along with dedifferentiation and transdifferentiation, for the process of tissue restoration. Several model systems are currently being investigated to determine the possibilities of using these adult quiescent reserve precursor cells for tissue engineering.
Subject(s)
Cell Differentiation/physiology , Germ Layers/cytology , Pluripotent Stem Cells/cytology , Regeneration/physiology , Tissue Engineering , Transcription Factors , Animals , Antigens, Surface/metabolism , Bone and Bones/metabolism , Cattle , Cell Lineage/physiology , Cellular Senescence/physiology , Connective Tissue/physiology , DNA-Binding Proteins/metabolism , Diabetes Mellitus/therapy , Embryo, Mammalian , Embryo, Nonmammalian , Extremities/physiology , Genetic Therapy , Hematopoietic Stem Cell Transplantation , Humans , Muscle, Skeletal/metabolism , Muscle, Skeletal/transplantation , Myocardial Infarction/therapy , Myogenin/metabolism , Neurodegenerative Diseases/therapy , Octamer Transcription Factor-3 , Pluripotent Stem Cells/transplantation , Rats , Telomerase/metabolism , Urodela/growth & development , Urodela/physiologyABSTRACT
BACKGROUND: The capacity of inflammatory cells to adhere involves an array of adhesion molecules, and is critical to the inflammatory responses seen in childhood asthma. We aimed to determine the changes of intercellular adhesion molecule-1 (ICAM-1) and L-selectin expressed on peripheral blood (PB) T lymphocytes and natural killer (NK) cells in asthmatic children with acute exacerbation and after prednisolone therapy. METHODS: Flow cytometric analysis was performed to determine the expression of ICAM-1 (CD54) and L-selectin (CD62L) on T (CD3+) cells and NK (CD3-/CD56+) cells of PB from children with allergic asthma with acute exacerbation and in a stable condition after prednisolone therapy. Atopic subjects without asthma and age-matched controls were also included for comparison. RESULTS: Percentages of PB non-CD3, CD56+ NK cells, but not CD3+ T cells, increased in asthmatic children with acute exacerbation, compared to those assessed in a stable condition after a course of prednisolone. However, significant decrease of ICAM-1 (P = 0.01) and L-selectin (P = 0.01) expression on PB NK cells, but not on T cells, were found in children with acute asthma compared to those in a stable condition. NK cells in children with acute asthma showed minimal expression of CD69 and CD25. CONCLUSIONS: Results suggests that either NK cells expressing ICAM-1 and L-selectin selectively migrated into inflamed lung tissues, or subsets of NK cells not expressing ICAM-1/L-selectin were expanded during acute exacerbation of childhood asthma.
Subject(s)
Asthma/metabolism , Intercellular Adhesion Molecule-1/biosynthesis , Intercellular Adhesion Molecule-1/blood , Killer Cells, Natural/metabolism , L-Selectin/biosynthesis , L-Selectin/blood , Acute Disease , Antigens, CD/biosynthesis , Antigens, CD/blood , Antigens, CD/drug effects , Antigens, Differentiation, T-Lymphocyte/biosynthesis , Antigens, Differentiation, T-Lymphocyte/blood , Antigens, Differentiation, T-Lymphocyte/drug effects , Asthma/blood , Asthma/drug therapy , Biomarkers/blood , CD3 Complex/biosynthesis , CD3 Complex/blood , CD3 Complex/drug effects , Child , Child Welfare , Child, Preschool , Glucocorticoids/therapeutic use , Humans , Intercellular Adhesion Molecule-1/drug effects , Killer Cells, Natural/drug effects , L-Selectin/drug effects , Lectins, C-Type , Prednisolone/therapeutic use , Receptors, Interleukin-2/biosynthesis , Receptors, Interleukin-2/blood , Receptors, Interleukin-2/drug effects , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , TaiwanABSTRACT
The clinical manifestations of acute organic arsenic intoxication in humans have seldom been described and the associated treatment has been thought to be the same as that of acute inorganic arsenic intoxication. We have studied a collection of patients from 1996 to 2001 who called the Poison Control Center of Kaohsiung Medical University Hospital asking for information regarding acute organic arsenic intoxication. The 17 patients ranged in age from 23 to 64 years old, with 5 females and 12 males. The cause of arsenic ingestion was attempted suicide. Abdominal pain and vomiting were the main symptoms. There were no differences in results between patients treated with and those treated without chelating agents. We therefore believe that the results of acute organic intoxication are not same as acute inorganic intoxication and it is unnecessary to use chelating agents in such conditions.