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1.
Nature ; 606(7916): 960-967, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35705808

RESUMO

Among the caspases that cause regulated cell death, a unique function for caspase-7 has remained elusive. Caspase-3 performs apoptosis, whereas caspase-7 is typically considered an inefficient back-up. Caspase-1 activates gasdermin D pores to lyse the cell; however, caspase-1 also activates caspase-7 for unknown reasons1. Caspases can also trigger cell-type-specific death responses; for example, caspase-1 causes the extrusion of intestinal epithelial cell (IECs) in response to infection with Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium)2,3. Here we show in both organoids and mice that caspase-7-deficient IECs do not complete extrusion. Mechanistically, caspase-7 counteracts gasdermin D pores and preserves cell integrity by cleaving and activating acid sphingomyelinase (ASM), which thereby generates copious amounts of ceramide to enable enhanced membrane repair. This provides time to complete the process of IEC extrusion. In parallel, we also show that caspase-7 and ASM cleavage are required to clear Chromobacterium violaceum and Listeria monocytogenes after perforin-pore-mediated attack by natural killer cells or cytotoxic T lymphocytes, which normally causes apoptosis in infected hepatocytes. Therefore, caspase-7 is not a conventional executioner but instead is a death facilitator that delays pore-driven lysis so that more-specialized processes, such as extrusion or apoptosis, can be completed before cell death. Cells must put their affairs in order before they die.


Assuntos
Caspase 7 , Perforina , Proteínas de Ligação a Fosfato , Proteínas Citotóxicas Formadoras de Poros , Esfingomielina Fosfodiesterase , Animais , Apoptose , Caspase 7/metabolismo , Chromobacterium/imunologia , Células Epiteliais/citologia , Intestinos/citologia , Células Matadoras Naturais/imunologia , Listeria monocytogenes/imunologia , Camundongos , Organoides , Perforina/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Esfingomielina Fosfodiesterase/metabolismo , Linfócitos T Citotóxicos/imunologia
2.
Anal Chem ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38917347

RESUMO

The annotation of metabolites detected in LC-MS-based untargeted metabolomics studies routinely applies accurate m/z of the intact metabolite (MS1) as well as chromatographic retention time and MS/MS data. Electrospray ionization and transfer of ions through the mass spectrometer can result in the generation of multiple "features" derived from the same metabolite with different m/z values but the same retention time. The complexity of the different charged and neutral adducts, in-source fragments, and charge states has not been previously and deeply characterized. In this paper, we report the first large-scale characterization using publicly available data sets derived from different research groups, instrument manufacturers, LC assays, sample types, and ion modes. 271 m/z differences relating to different metabolite feature pairs were reported, and 209 were annotated. The results show a wide range of different features being observed with only a core 32 m/z differences reported in >50% of the data sets investigated. There were no patterns reporting specific m/z differences that were observed in relation to ion mode, instrument manufacturer, LC assay type, and mammalian sample type, although some m/z differences were related to study group (mammal, microbe, plant) and mobile phase composition. The results provide the metabolomics community with recommendations of adducts, in-source fragments, and charge states to apply in metabolite annotation workflows.

3.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33737395

RESUMO

Acute kidney injury is highly prevalent and associated with high morbidity and mortality, and there are no approved drugs for its prevention and treatment. Vagus nerve stimulation (VNS) alleviates inflammatory diseases including kidney disease; however, neural circuits involved in VNS-induced tissue protection remain poorly understood. The vagus nerve, a heterogeneous group of neural fibers, innervates numerous organs. VNS broadly stimulates these fibers without specificity. We used optogenetics to selectively stimulate vagus efferent or afferent fibers. Anterograde efferent fiber stimulation or anterograde (centripetal) sensory afferent fiber stimulation both conferred kidney protection from ischemia-reperfusion injury. We identified the C1 neurons-sympathetic nervous system-splenic nerve-spleen-kidney axis as the downstream pathway of vagus afferent fiber stimulation. Our study provides a map of the neural circuits important for kidney protection induced by VNS, which is critical for the safe and effective clinical application of VNS for protection from acute kidney injury.


Assuntos
Injúria Renal Aguda/etiologia , Suscetibilidade a Doenças , Neuroimunomodulação , Baço/imunologia , Baço/inervação , Estimulação do Nervo Vago , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Camundongos , Neurônios , Sistema Nervoso Simpático/fisiologia
4.
Proc Natl Acad Sci U S A ; 116(52): 26768-26778, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31843910

RESUMO

Natural killer (NK) cells mediate vital control of cancer and viral infection. They rely on MHC class I (MHC I)-specific self-receptors to identify and lyse diseased cells without harming self-MHC I-bearing host cells. NK cells bearing inhibitory self-receptors for host MHC I also undergo education, referred to as licensing, which causes them to become more responsive to stimulation via activation receptor signaling. Previous work has shown that licensed NK cells selectively expand during virus infections and they are associated with improved clinical response in human patients experiencing certain chronic virus infections, including HIV and hepatitis C virus. However, the importance of inhibitory self-receptors in NK-mediated virus immunity is debated as they also limit signals in NK cells emanating from virus-specific activation receptors. Using a mouse model of MHC I-dependent (H-2Dk) virus immunity, we discovered that NK cells depend on the Ly49G2 inhibitory self-receptor to mediate virus control, which coincided with host survival during murine cytomegalovirus infection. This antiviral effect further requires active signaling in NK cells via the Ly49R activation receptor that also binds H-2Dk. In tandem, these functionally discordant Ly49 self-receptors increase NK cell proliferation and effector activity during infection, resulting in selective up-regulation of CD25 and KLRG1 in virus-specific Ly49R+ Ly49G2+ NK cells. Our findings establish that paired self-receptors act as major determinants of NK cell-mediated virus sensing and immunity.

5.
Am J Physiol Renal Physiol ; 319(1): F125-F138, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32508112

RESUMO

Acute kidney injury (AKI) is an important clinical disorder with high prevalence, serious consequences, and limited therapeutic options. Modulation of neuroimmune interaction by nonpharmacological methods is emerging as a novel strategy for treating inflammatory diseases, including AKI. Recently, pulsed ultrasound (US) treatment was shown to protect from AKI by stimulating the cholinergic anti-inflammatory pathway. Because of the relatively simple, portable, and noninvasive nature of US procedures, US stimulation may be a valuable therapeutic option for treating inflammatory conditions. This review discusses potential impacts of US bioeffects on the nervous system and how this may generate feedback onto the immune system. We also discuss recent evidence supporting the use of US as a means to treat AKI and other inflammatory diseases.


Assuntos
Injúria Renal Aguda/terapia , Neuroimunomodulação , Ultrassonografia de Intervenção/métodos , Humanos , Inflamação/terapia
6.
J Trauma Stress ; 32(3): 465-470, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31173669

RESUMO

The most robust finding of moral injury (MI) research thus far-that past exposure to potentially morally injurious events predicts current symptoms of posttraumatic stress disorder (PTSD)-challenges conceptions that trauma is exclusively the result of fear-evoking brushes with death or sexual assault. It also calls into question the applicability to MI of treatments for PTSD grounded in the fear model of trauma. In the current article, two divergent theoretical models that have been applied to the understanding and treatment of moral injury are compared: the stress-appraisal-coping model and the stress injury model. Attention is drawn to the differences between how these models conceptualize stress and distress, including psychological trauma, and to their potential implications for the sustainment of mental health stigma, especially in military and veteran populations.


Assuntos
Transtornos de Estresse Pós-Traumáticos/psicologia , Humanos , Projetos de Pesquisa/tendências , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/terapia
7.
Eur J Orthop Surg Traumatol ; 29(8): 1705-1708, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31292717

RESUMO

Most knee osteoarthritis and meniscectomy studies focus on osteoarthritis in the tibiofemoral joint and ignore the patellofemoral joint. This study aims to assess the long-term effects of total meniscectomy on the patellofemoral joint. To our knowledge, this is the only study of osteoarthritis in the patellofemoral joint following meniscectomy that extends to a 40-year follow-up period. Twenty-two patients with osteoarthritis were evaluated at a mean of 40 years post-meniscectomy using standardised weight-bearing radiographs of the operated and non-operated knees. Patellofemoral joint osteoarthritis was diagnosed by the presence of osteophytes and joint space narrowing to less than 5 mm. Kellgren and Lawrence scores were calculated from the radiographs. Patellofemoral joint osteoarthritis and tibiofemoral joint osteoarthritis were correlated with International Knee Documentation Committee scores and range of movement measurements. A significant difference was observed between the operated and non-operated knees in terms of patellofemoral joint osteophyte formation. There was a significant difference in tibiofemoral joint Kellgren and Lawrence scores, International Knee Documentation Committee scores and range of movement measurements between knees with lateral facet patellofemoral joint space of < 5 mm and > 5 mm. This study shows an association between open total meniscectomy and patellofemoral joint osteoarthritis at 40 years following surgery. There was also an association between patellofemoral joint space narrowing in the lateral facet and tibiofemoral joint osteoarthritis. Possible causes include altered biomechanical loading patterns following meniscectomy as well as global processes within the knee.


Assuntos
Meniscectomia , Meniscos Tibiais/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Articulação Patelofemoral/diagnóstico por imagem , Adolescente , Idoso , Seguimentos , Humanos , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Osteófito/diagnóstico por imagem , Medidas de Resultados Relatados pelo Paciente , Radiografia , Amplitude de Movimento Articular
8.
PLoS Pathog ; 12(2): e1005419, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26845690

RESUMO

The MHC class I D(k) molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds D(k), are required to control viral spread. The extent of D(k)-dependent host resistance, however, differs significantly amongst related strains of mice, C57L and MA/My. As a result, we predicted that relatively small-effect modifier genetic loci might together shape immune cell features, NK cell reactivity, and the host immune response to MCMV. A robust D(k)-dependent genetic effect, however, has so far hindered attempts to identify additional host resistance factors. Thus, we applied genomic mapping strategies and multicolor flow cytometric analysis of immune cells in naive and virus-infected hosts to identify genetic modifiers of the host immune response to MCMV. We discovered and validated many quantitative trait loci (QTL); these were mapped to at least 19 positions on 16 chromosomes. Intriguingly, one newly discovered non-MHC locus (Cmv5) controlled splenic NK cell accrual, secondary lymphoid organ structure, and lymphoid follicle development during MCMV infection. We infer that Cmv5 aids host resistance to MCMV infection by expanding NK cells needed to preserve and protect essential tissue structural elements, to enhance lymphoid remodeling and to increase viral clearance in spleen.


Assuntos
Infecções por Citomegalovirus/imunologia , Genes MHC Classe I/genética , Células Matadoras Naturais/imunologia , Muromegalovirus/imunologia , Locos de Características Quantitativas/genética , Receptores Imunológicos/genética , Animais , Mapeamento Cromossômico , Infecções por Citomegalovirus/patologia , Feminino , Genes MHC Classe I/imunologia , Loci Gênicos , Genótipo , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Imunidade Celular , Tecido Linfoide/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polimorfismo Genético , Receptores Imunológicos/metabolismo , Baço/imunologia , Baço/patologia
9.
J Trauma Stress ; 30(3): 259-269, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28470977

RESUMO

The meaningful interpretation of longitudinal study findings requires temporal stability of the constructs assessed (i.e., measurement invariance). We sought to examine measurement invariance of the construct of posttraumatic stress disorder (PTSD) as based on the Diagnostic and Statistical Manual of Mental Disorders indexed by the PTSD Checklist (PCL) and the Clinician-Administered PTSD Scale (CAPS) in a sample of 834 Marines with significant combat experience. PTSD was assessed 1-month predeployment (T0), and again at 1-month (T1), 5-months (T2), and 8-months postdeployment (T3). We tested configural (pattern of item/parcel loadings), metric (item/parcel loadings on latent factors), and scalar (item/parcel-level severity) invariance and explored sources of measurement instability (partial invariance testing). The T0 best-fitting emotional numbing model factor structure informed the conceptualization of PTSD's latent factors and parcel formations. We found (1) scalar noninvariance for the construct of PTSD as measured by the PCL and the CAPS, and for PTSD symptom clusters as assessed by the CAPS; and (2) metric noninvariance for PTSD symptom clusters as measured by the PCL. Exploratory analyses revealed factor-loading and intercept differences from pre- to postdeployment for avoidance symptoms, numbing symptoms (mainly psychogenic amnesia and foreshortened future), and the item assessing startle, each of which reduced construct stability. Implications of these findings for longitudinal studies of PTSD are discussed.


Assuntos
Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Campanha Afegã de 2001- , Manual Diagnóstico e Estatístico de Transtornos Mentais , Análise Fatorial , Humanos , Guerra do Iraque 2003-2011 , Estudos Longitudinais , Masculino , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Autorrelato , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Estados Unidos , Adulto Jovem
10.
J Foot Ankle Surg ; 55(5): 1024-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26261069

RESUMO

Toe syndactyly is a common congenital malformation affecting approximately 1 in 2000 people and can cause significant emotional and psychological distress for the patient. We report a case of a 41-year-old female who was concerned about the aesthetic appearance of her bilateral second and third toe with incomplete, simple syndactyly and had requested surgical correction. A number of operative techniques have been described in the orthopedic and plastic surgery data, with no one technique proving superior. We used medical tattooing to create the appearance of a complete interdigital cleft. This low-risk, and low-cost procedure resulted in a satisfactory outcome for the patient. To the best of our knowledge, this is the first reported case using this technique, which we propose as a simple alternative to surgical correction of toe syndactyly.


Assuntos
Redução de Custos , Sindactilia/terapia , Tatuagem/métodos , Adulto , Técnicas Cosméticas , Estética , Feminino , Deformidades Congênitas do Pé/diagnóstico , Deformidades Congênitas do Pé/terapia , Humanos , Sindactilia/diagnóstico , Tatuagem/economia , Dedos do Pé/anormalidades , Resultado do Tratamento
11.
Eur J Immunol ; 44(11): 3273-82, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25187217

RESUMO

Ly49G2 (G2+) NK cells mediate murine (M)CMV resistance in MHC D(k) -expressing mice. Bone marrow transplantation (BMT) studies revealed that G2+ NK cell-mediated MCMV resistance requires D(k) in both hematopoietic and nonhematopoietic cells. As a Ly49G2 ligand, D(k) in both cell lineages may contribute to lysis of virus-infected cells. Alternatively, cellular differences in self-MHC D(k) may have affected NK-cell education, and consequently NK cell-mediated viral clearance. We investigated the D(k) -licensing effect on BM-derived NK cells in BMT recipients by analyzing cytokines, cytotoxicity and MCMV resistance. In BMT recipients with lineage-restricted D(k) , G2+ NK-cell reactivity and cytotoxicity was diminished in comparison to BMT recipients with self-MHC in all cells. Reduced G2+ NK-mediated MCMV resistance in BMT recipients with lineage-restricted self-MHC indicates that licensing of G2+ NK cells is related to NK-cell reactivity and viral control. Titrating donor BM with self-MHC-bearing hematopoietic cells, as well as adoptive transfer of mature G2+ NK cells into BMT recipients with self-MHC in non-hematopoietic cells only, enhanced NK-cell licensing and rescued MCMV resistance. This disparate self-MHC NK-cell education model would suggest that inadequately licensed NK cells corresponded to inefficient viral sensing and clearance.


Assuntos
Infecções por Herpesviridae/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Células Matadoras Naturais/imunologia , Muromegalovirus/imunologia , Células 3T3 , Transferência Adotiva , Animais , Transplante de Medula Óssea , Linhagem Celular , Linhagem da Célula/imunologia , Células Matadoras Naturais/transplante , Camundongos , Camundongos Endogâmicos C57BL , Subfamília A de Receptores Semelhantes a Lectina de Células NK/metabolismo
12.
J Immunol ; 191(9): 4709-19, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24068668

RESUMO

MHC class I D(k) and Ly49G2 (G2) inhibitory receptor-expressing NK cells are essential to murine CMV (MCMV) resistance in MA/My mice. Without D(k), G2(+) NK cells in C57L mice fail to protect against MCMV infection. As a cognate ligand of G2, D(k) licenses G2(+) NK cells for effector activity. These data suggested that D(k)-licensed G2(+) NK cells might recognize and control MCMV infection. However, a role for licensed NK cells in viral immunity is uncertain. We combined classical genetics with flow cytometry to visualize the host response to MCMV. Immune cells collected from individuals of a diverse cohort of MA/My × C57L offspring segregating D(k) were examined before infection and postinfection, including Ly49(+) NK subsets, receptor expression features, and other phenotypic traits. To identify critical NK cell features, automated analysis of 110 traits was performed in R using the Pearson correlation, followed with a Bonferroni correction for multiple tests. Hierarchical clustering of trait associations and principal component analyses were used to discern shared immune response and genetic relationships. The results demonstrate that G2 expression on naive blood NK cells was predictive of MCMV resistance. However, rapid G2(+) NK cell expansion following viral exposure occurred selectively in D(k) offspring; this response was more highly correlated with MCMV control than all other immune cell features. We infer that D(k)-licensed G2(+) NK cells efficiently detected missing-self MHC cues on viral targets, which elicited cellular expansion and target cell killing. Therefore, MHC polymorphism regulates licensing and detection of viral targets by distinct subsets of NK cells required in innate viral control.


Assuntos
Infecções por Herpesviridae/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Células Matadoras Naturais/imunologia , Muromegalovirus/imunologia , Animais , Antígenos Ly/metabolismo , Genes MHC Classe I/genética , Genótipo , Infecções por Herpesviridae/virologia , Antígenos de Histocompatibilidade Classe I/genética , Camundongos , Camundongos Endogâmicos C57BL , Subfamília A de Receptores Semelhantes a Lectina de Células NK/metabolismo , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo
13.
J Trauma Stress ; 28(1): 73-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25630586

RESUMO

Large cohort studies suggest that most military personnel experience minimal posttraumatic stress disorder (PTSD) symptoms following warzone deployment, an outcome often labeled resilience. Very low symptom levels, however, may be a marker for low exposure, not resilience, which requires relatively high-magnitude or high-frequency stress exposure as a precondition. We used growth mixture modeling (GMM) to examine the longitudinal course of lifetime PTSD symptoms following combat exposure by disaggregating deployed U.S. Marines into upper, middle, and lower tertiles of combat exposure. All factor models fit the data well; Tucker-Lewis Index (TLI) and comparative fit index (CFI) values ranged from .91 to .97. Three distinct trajectories best explained the data within each tertile. The upper tertile comprised True Resilience (73.2%), New-Onset Symptoms (18.3%), and Pre-existing Symptoms (8.5%) trajectories. The middle tertile also comprised True Resilience (74.5%), New-Onset Symptoms (16.1%), and Pre-existing Symptoms (9.4%) trajectories. The lower tertile comprised Artifactual Resilience (86.3%), Pre-existing Symptoms (7.6%), and New-Onset Symptoms (6.1%) trajectories. True Resilience involved a clinically significant symptom increase followed by a return to baseline, whereas Artifactual Resilience involved consistently low symptoms. Conflating artifactual and true resilience may inaccurately create the expectation of persistently low symptoms regardless of warzone exposure.


Assuntos
Exposição à Violência/psicologia , Militares/psicologia , Resiliência Psicológica , Transtornos de Estresse Pós-Traumáticos/psicologia , Adolescente , Adulto , Humanos , Estudos Longitudinais , Masculino , Modelos Psicológicos , Medicina Naval , Prognóstico , Escalas de Graduação Psiquiátrica , Estados Unidos , Guerra , Adulto Jovem
14.
Int J Health Care Qual Assur ; 27(1): 36-43, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24660516

RESUMO

PURPOSE: The hip fracture "best practice tariff" (BPT) came into effect in April 2010. It advocated two key improvements: surgery within 36 hrs of arrival in the emergency department; and multi-disciplinary care directed by ortho-geriatrician from admission to discharge. The aim of this paper is to look at the 36 hours to operation target and its implications for orthopaedic department trauma service staff in a busy district general hospital, and to evaluate the measures implemented to meet the target. DESIGN/METHODOLOGY/APPROACH: Trauma-list data, collected from a theatre management system, was compared with trauma patients placed on elective and emergency lists, before and after designated daily trauma lists were implemented. FINDINGS: After a designated daily trauma list was introduced, a significant rise (from 56 per cent to 85 per cent) became evident in the proportion of patients operated on within 36 hrs, between November 2010 to February 2011, while hip fracture cases managed on the elective list fell from 24 per cent to 17 per cent. PRACTICAL IMPLICATIONS: Despite adding a half-day trauma list, the trauma service has insufficient capacity to achieve the new BPT for all hip fracture patients in the hospital. Therefore, there is a significant knock-on effect for managing patient overspill on elective services. Will the significant changes in service provision designed to achieve this BPT be cost effective? ORIGINALITY/VALUE: This paper aims to answer how busy department staff address an issue that professionals in every English hospital are facing.


Assuntos
Serviço Hospitalar de Emergência/organização & administração , Fraturas do Colo Femoral/cirurgia , Centro Cirúrgico Hospitalar/organização & administração , Tempo para o Tratamento/normas , Benchmarking/métodos , Benchmarking/normas , Benchmarking/estatística & dados numéricos , Serviço Hospitalar de Emergência/normas , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais Gerais/organização & administração , Hospitais Gerais/normas , Hospitais Gerais/estatística & dados numéricos , Humanos , Estudos de Casos Organizacionais , Estudos Retrospectivos , Centro Cirúrgico Hospitalar/normas , Centro Cirúrgico Hospitalar/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Reino Unido
15.
Pediatr Dent ; 46(1): 52-57, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449037

RESUMO

Purpose: To determine the effect of potassium iodide (KI) on the black/gray staining caused by silver diammine fluoride (SDF) when applied to carious lesions. Methods: Extracted caries-free molar surfaces had caries induced to examine the use of SDF and SDF followed by KI (SDF+KI) on extracted permanent molars that had caries induced on their surfaces and were monitored for a period after application. To monitor the color changes, CIELAB color space readings???a color space defined by the International Commission on Illumination???were used. The system is composed of three values, of which the L* measures black to white across a span of zero (black) to 100 (white). Measurements were taken at eight intervals between days zero to 72. Results: L* values were found to be significantly different between SDF and SDF+KI groups and from baseline. On average, the SDF+KI group versus the SDF group was 9.47 units lighter. Conclusion: The findings indicate the application of silver diammine fluoride followed by potassium iodide can reduce the black staining SDF alone causes, potentially making it a viable esthetic option for patients with anterior tooth caries.


Assuntos
Amônia , Cárie Dentária , Potássio , Compostos de Amônio Quaternário , Compostos de Prata , Humanos , Iodeto de Potássio , Fluoretos , Cárie Dentária/prevenção & controle , Coloração e Rotulagem , Fluoretos Tópicos
16.
BMC Psychiatry ; 13: 9, 2013 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-23289606

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) is one of the most commonly observed stress-related conditions following combat exposure and its effective prevention is a high health-care priority. Reports of peritraumatic reactions have been shown to be highly associated with PTSD among combat exposed service members. However, existing instruments measuring peritraumatic symptoms were not specifically developed to assess combat-related peritraumatic stress and each demonstrates a different peritraumatic focus. We therefore developed the Peritraumatic Behavior Questionnaire (PBQ), a new military-specific rating scale focused upon the wide range of symptoms suggestive of combat-related peritraumatic distress in actively deployed Service Members. This study describes the development of the PBQ and reports on the psychometric properties of its self-rated version (PBQ-SR). METHODS: 688 Marine infantry service members were retrospectively assessed by the PBQ-SR within the scope of the Marine Resiliency Study after their deployment to war zone. Participants have been additionally assessed by a variety of questionnaires, as well as clinical interviews both pre and post-deployment. RESULTS: The PBQ-SR demonstrated satisfactory internal consistency, convergent and discriminant validity, as well as high correlation with trait dissociation prior to deployment. Component analysis suggested a latent bi-dimensional structure separating a peritraumatic emotional distress and physical awareness factor. The PBQ-SR total score showed high correlation to general anxiety, depression, poorer general health and posttraumatic symptoms after deployment and remained a significant predictor of PTSD severity, after controlling for those measures. The suggested screening cut-off score of 12 points demonstrated satisfactory predictive power. CONCLUSIONS: This study confirms the ability of the PBQ-SR to unify the underlying peritraumatic symptom dimensions and reliably assess combat-related peritraumatic reaction as a general construct. The PBQ-SR demonstrated promise as a potential standard screening measure in military clinical practice, while It's predictive power should be established in prospective studies.


Assuntos
Distúrbios de Guerra/psicologia , Distúrbios de Guerra/diagnóstico , Análise Fatorial , Humanos , Masculino , Militares/psicologia , Escalas de Graduação Psiquiátrica , Psicometria , Reprodutibilidade dos Testes , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
17.
Nat Genet ; 36(12): 1268-74, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15531882

RESUMO

Salmonella enterica serovars often have a broad host range, and some cause both gastrointestinal and systemic disease. But the serovars Paratyphi A and Typhi are restricted to humans and cause only systemic disease. It has been estimated that Typhi arose in the last few thousand years. The sequence and microarray analysis of the Paratyphi A genome indicates that it is similar to the Typhi genome but suggests that it has a more recent evolutionary origin. Both genomes have independently accumulated many pseudogenes among their approximately 4,400 protein coding sequences: 173 in Paratyphi A and approximately 210 in Typhi. The recent convergence of these two similar genomes on a similar phenotype is subtly reflected in their genotypes: only 30 genes are degraded in both serovars. Nevertheless, these 30 genes include three known to be important in gastroenteritis, which does not occur in these serovars, and four for Salmonella-translocated effectors, which are normally secreted into host cells to subvert host functions. Loss of function also occurs by mutation in different genes in the same pathway (e.g., in chemotaxis and in the production of fimbriae).


Assuntos
Evolução Molecular , Variação Genética , Genoma Bacteriano , Mutação/genética , Salmonella paratyphi A/genética , Salmonella typhi/genética , Sequência de Bases , Biblioteca Gênica , Componentes Genômicos/genética , Humanos , Análise em Microsséries , Dados de Sequência Molecular , Pseudogenes/genética , Análise de Sequência de DNA , Especificidade da Espécie
18.
J Orthop Traumatol ; 14(3): 159-64, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23649817

RESUMO

BACKGROUND: Does below-knee symptomatic muscular (gastrocnemius or soleus) vein thrombosis (MVT) warrant investigation and treatment in post-operative orthopaedic patients? We performed a literature search and evaluated the evidence looking for guidance regarding this question. MATERIALS AND METHODS: We performed a literature search with the use of PubMed, Medline and Google Scholar from 1950 to September 2011. Search terms included "muscular vein thrombosis" (MVT) and "isolated gastrocnemius or soleus vein thrombosis" (IGSVT). We reviewed the eight level II studies relevant to our search, only one of which was in a specific orthopaedic population. RESULTS: Studies looking at the rates of progression of isolated MVT have shown conflicting results. There is also a lack of consensus between studies that compare progression amongst groups with or without anticoagulant treatment. The majority of the studies do not distinguish between medical, surgical or orthopaedic patients. CONCLUSIONS: We cannot confidently recommend commencement of anticoagulation treatment upon identification of MVT in post-operative orthopaedic patients. We can only suggest that, once MVT is diagnosed, the patient should undergo serial ultrasound scan (USS) duplex scans, and if propagation is identified, then treatment may be deemed beneficial. LEVEL OF EVIDENCE: III (review of non-randomized controlled cohort/follow-up studies).


Assuntos
Anticoagulantes/uso terapêutico , Músculo Esquelético/irrigação sanguínea , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Medição de Risco , Fatores de Risco , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologia
19.
Nephron ; 147(1): 39-43, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36108596

RESUMO

BACKGROUND: Myeloid cells form an important element of the response to ischemia-reperfusion injury (IRI). While the mononuclear phagocyte system is complex and difficult to study, our knowledge of the cells involved and their impacts has been steadily increasing. However, there is still need to rigorously define and separate the functions of discreet myeloid populations in the kidney. The relatively recent distinction between resident macrophages and infiltrating monocytes in the kidney is an important advance that will enhance our understanding of the various roles of distinct myeloid populations, but specific tools are needed to rigorously define the contributions of each to injury, repair, and the transition to chronic disease. SUMMARY: Resident macrophages in the kidney form a network with various supportive roles during development and homeostasis. While the classification of these cells has been frequently convoluted in the literature, evidence for their roles during injury and repair is starting to accumulate. Current indications suggest they may have a minimal role during injury processes but may be important during the recovery phase. However, their involvement may also be dependent on their activation state in response to environmental cues. Investigations of the M1/M2 phenotype of myeloid cells have shed some light on the phenotypes that contribute to the manifestation of injury and/or recovery, but it is still difficult to form detailed conclusions. Here we will discuss the potential involvement of resident cells in these processes and the use of the M1/M2 system for defining the myeloid response following IRI. KEY MESSAGES: There is a need for additional specific analysis of the contribution of resident versus recruited myeloid cells to injury, recovery, and chronic disease in the kidney. In addition, the contribution of myeloid activation states that extend beyond simple M1/M2 classification is an important area that needs close attention. Our ability to assess resident cells is growing, and awareness of the shortcoming of the M1/M2 system is also increasing. These are promising developments which bode well for the future of kidney injury and disease research.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Humanos , Rim , Macrófagos , Monócitos
20.
Prev Chronic Dis ; 9: E97, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22575082

RESUMO

The Marine Resiliency Study (MRS) is a prospective study of factors predictive of posttraumatic stress disorder (PTSD) among approximately 2,600 Marines in 4 battalions deployed to Iraq or Afghanistan. We describe the MRS design and predeployment participant characteristics. Starting in 2008, our research team conducted structured clinical interviews on Marine bases and collected data 4 times: at predeployment and at 1 week, 3 months, and 6 months postdeployment. Integrated with these data are medical and career histories from the Career History Archival Medical and Personnel System (CHAMPS) database. The CHAMPS database showed that 7.4% of the Marines enrolled in MRS had at least 1 mental health diagnosis. Of enrolled Marines, approximately half (51.3%) had prior deployments. We found a moderate positive relationship between deployment history and PTSD prevalence in these baseline data.


Assuntos
Militares/psicologia , Resiliência Psicológica , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Campanha Afegã de 2001- , Distúrbios de Guerra/diagnóstico , Distúrbios de Guerra/psicologia , Coleta de Dados , Bases de Dados Factuais , Emoções , Humanos , Entrevistas como Assunto , Guerra do Iraque 2003-2011 , Valor Preditivo dos Testes , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários , Ferimentos e Lesões
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