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2.
Disabil Rehabil ; : 1-10, 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37415395

RESUMO

PURPOSE: We performed a systematic review to assess the psychometric properties of extended Activities of Daily Living (eADL) scales. MATERIALS AND METHODS: Articles assessing eADL scales' properties were retrieved by searching multidisciplinary databases, and reference screening. Data on the following properties were extracted: validity, reliability, responsiveness, and internal consistency. The COSMIN (Consensus-based Standards for the selection of health status Measurement Instruments) risk of bias checklists are used to assess the quality of included articles. All aspects were performed by two independent researchers. RESULTS: Of 245 titles, 26 articles were eligible, comprising 15 different eADL scales. The Lawton scale had the most papers describing properties, while the Performance-based Instrumental Activities of Daily Living received the highest COSMIN rating. Properties most often assessed were convergent validity and reliability, no articles assessed all COSMIN properties. The COSMIN assessment rated 43% of the properties as 'positive', 31% 'doubtful' and 26% 'inadequate'. Only Lawton was assessed in more than one paper, available data suggest that this scale has excellent reliability, construct validity, internal consistency, and medium criterion validity. CONCLUSION: Despite their common use, there are limited data on the properties of eADL scales. Where data are available there are potential methodological issues in the studies.Implications for RehabilitationThe functional abilities of older adults are most commonly measured using extended activities of daily living scales (eADL).There are many eADL scales available to clinicians and no guidance on a preferred tool.Despite the frequent use of eADL scales in research and practice, there is limited published literature on their psychometric properties (for example validity, reliability and responsiveness).The Lawton Scale has the most supporting evidence and its properties are generally acceptable, more research is needed on other eADL scales.

3.
Curr Psychiatry Rep ; 25(1): 7-11, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454501

RESUMO

PURPOSEOF REVIEW: This article explores the emerging role of compassion in the treatment of individuals who have caused sexual harm. It also brings focus to the importance of self-care and self-compassion for the practitioners who do this work. RECENT FINDINGS: Early studies into interventions designed to prevent offending behavior focused more on risk reduction than client resilience and well-being. The good lives model shifted focus to rehabilitation centered on clients' strengths. Recent critiques highlight the importance of compassion in treatment and self-compassion for practitioners working in this field. Compassion plays a fundamental role in therapy with clients who have caused sexual harm.


Assuntos
Empatia , Autocompaixão , Humanos , Comportamento Sexual
4.
Elife ; 112022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36125130

RESUMO

During obesity and high fat-diet (HFD) feeding in mice, sustained low-grade inflammation includes not only increased pro-inflammatory macrophages in the expanding adipose tissue, but also bone marrow (BM) production of invasive Ly6Chigh monocytes. As BM adiposity also accrues with HFD, we explored the relationship between the gains in BM white adipocytes and invasive Ly6Chigh monocytes by in vivo and ex vivo paradigms. We find a temporal and causal link between BM adipocyte whitening and the Ly6Chigh monocyte surge, preceding the adipose tissue macrophage rise during HFD in mice. Phenocopying this, ex vivo treatment of BM cells with conditioned media from BM adipocytes or bona fide white adipocytes favoured Ly6Chigh monocyte preponderance. Notably, Ly6Chigh skewing was preceded by monocyte metabolic reprogramming towards glycolysis, reduced oxidative potential and increased mitochondrial fission. In sum, short-term HFD changes BM cellularity, resulting in local adipocyte whitening driving a gradual increase and activation of invasive Ly6Chigh monocytes.


Assuntos
Medula Óssea , Monócitos , Adipócitos , Animais , Meios de Cultivo Condicionados , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/metabolismo , Obesidade/metabolismo
5.
Sci Rep ; 11(1): 20571, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663882

RESUMO

Intestinal functions demonstrate circadian rhythms thought to be entrained, in part, by an organisms' intrinsic feeding and fasting periods as well as by the intestinal microbiome. Circadian disruption as a result of ill-timed nutrient exposure and obesogenic feeding poses an increased risk to disease. As such, the aim of this study was to assess the relationships between dietary timing, composition, and the microbiome with regard to rhythmic small intestinal structure and mucosal immunity. Rodent chow (RC)-mice exhibited time-dependent increases in small intestinal weight, villus height, and crypt depth as well as an increased proportion of CD8αα+ cells and concomitant decrease in CD8αß+ cells at the onset of the feeding period (p < 0.05-0.001). Western diet (WD)-animals displayed disrupted time-dependent patterns in intestinal structure and lymphocyte populations (p < 0.05-0.01). Antibiotic-induced microbial depletion abrogated the time- and diet-dependent patterns in both RC- and WD-mice (p < 0.05-0.001). However, although germ-free-mice displayed altered rhythms, fecal microbial transfer from RC-mice was generally unsuccessful in restoring structural and immune changes in these animals. This study shows that adaptive changes in the small intestine at the onset of the feeding and fasting periods are disrupted by WD-feeding, and that these changes are dependent, in part, on the intestinal microbiome.


Assuntos
Ritmo Circadiano/fisiologia , Microbioma Gastrointestinal/fisiologia , Intestino Delgado/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Disbiose/fisiopatologia , Jejum , Comportamento Alimentar/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/fisiopatologia
6.
Int J Offender Ther Comp Criminol ; 65(12): 1299-1315, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132910

RESUMO

User experience and client satisfaction is capturing more attention in the field of social services. The provision of treatment services to individuals convicted of sexual offenses, in particular, has expanded exponentially over the last 20 years. This growing population is now interviewed, interrogated, investigated, assessed, managed, treated, supervised, and surveilled, while their perspective as "service users" is almost entirely absent from research. To that end, this article introduces the service user voice within the context of society's responses to sexual offending. We conducted thematic analysis on secondary data from interviews with 93 individuals. These include 74 men from the United States and 19 men from the United Kingdom, all of whom had been convicted for sexual offenses. The original qualitative data from the two original studies were freshly analysed, inductively and deductively, using Thematic Analysis so that the themes, as well as resulting codes, were appropriate and fit for purpose. Specific themes emerged from each of three clear stages in their service user journey: (a) Interactions with the formal criminal justice system (police, courts, and custodial corrections), (b) Interactions with community corrections (probation and parole), and (c) Interactions with treatment providers (rehabilitation, therapists, and evaluators). We describe the service user experience at each stage and discuss how policy and practice can resolve areas of disconnection. We suggest several ways to promote and privilege the service user voice for those convicted of sexual crimes.


Assuntos
Criminosos , Delitos Sexuais , Humanos , Masculino , Comportamento Sexual , Reino Unido
7.
Proc Natl Acad Sci U S A ; 117(20): 10946-10957, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32350141

RESUMO

Four decades ago, it was identified that muramyl dipeptide (MDP), a peptidoglycan-derived bacterial cell wall component, could display immunosuppressive functions in animals through mechanisms that remain unexplored. We sought to revisit these pioneering observations because mutations in NOD2, the gene encoding the host sensor of MDP, are associated with increased risk of developing the inflammatory bowel disease Crohn's disease, thus suggesting that the loss of the immunomodulatory functions of NOD2 could contribute to the development of inflammatory disease. Here, we demonstrate that intraperitoneal (i.p.) administration of MDP triggered regulatory T cells and the accumulation of a population of tolerogenic CD103+ dendritic cells (DCs) in the spleen. This was found to occur not through direct sensing of MDP by DCs themselves, but rather via the production of the cytokine GM-CSF, another factor with an established regulatory role in Crohn's disease pathogenesis. Moreover, we demonstrate that populations of CD103-expressing DCs in the gut lamina propria are enhanced by the activation of NOD2, indicating that MDP sensing plays a critical role in shaping the immune response to intestinal antigens by promoting a tolerogenic environment via manipulation of DC populations.


Assuntos
Antígenos CD/metabolismo , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Tolerância Imunológica , Cadeias alfa de Integrinas/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Acetilmuramil-Alanil-Isoglutamina/genética , Acetilmuramil-Alanil-Isoglutamina/metabolismo , Animais , Doença de Crohn , Citocinas , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Proteína Adaptadora de Sinalização NOD2/genética , Linfócitos T Reguladores/metabolismo
8.
J Magn Reson ; 315: 106738, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32417414

RESUMO

In low-field magnetic resonance applications there is often an interest in creating homogeneous magnetic fields over unusual geometries, particularly when quantum magnetometers are involved. In this paper a design method is proposed, where both the surface current and magnetic field are expanded to find current coefficients that cancel out higher order field terms. Two coils are designed using this double expansion methodology: (1) a tuning field for a half-meter-long atomic magnetometer array and (2) a null field for a magnetometer to operate adjacent to an excitation solenoid. The field verification of the former shows the accuracy of CNC milling and the method proposed; a close analysis of the field signature in the latter revealed the limitations of 3D printing for precise scientific applications. Both coils are designed to be fifth-order error systems or better.

9.
Curr Psychiatry Rep ; 22(7): 35, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32462490

RESUMO

PURPOSE OF REVIEW: This paper explores how motivational interviewing (MI) can be useful to practitioners working with people who have sexually abused. Research has found that the most effective practitioners working with these clients are warm, empathic, rewarding, and directive. Putting these characteristics into practice, however, can be challenging for professionals in treatment settings. Despite a wealth of information regarding MI practice generally, its use with people who have sexually abused has received little attention. RECENT FINDINGS: Motivational interviewing has been found to be effective in helping people change a wide range of problematic behaviors. Although it has been found to assist in treatment engagement with people who have engaged in intimate partner violence, it has not been subjected to rigorous examination in the treatment of sexual aggression. Nonetheless, it has received increasing attention within criminal-justice circles and can help clients of all backgrounds become involved in many of the treatment services available to them. The most effective practitioners working with these clients are warm, empathic, rewarding, and directive. The practice of motivational interviewing can benefit clients directly and can help professionals to develop the characteristics found to work with people who have sexually abused.


Assuntos
Entrevista Motivacional , Transtornos Relacionados ao Uso de Substâncias , Agressão , Direito Penal , Humanos , Comportamento Sexual
10.
Blood Adv ; 3(10): 1622-1637, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31138591

RESUMO

Polymorphonuclear neutrophils (PMNs) are the most abundant circulating leukocytes, and the first cells recruited to sites of tissue inflammation. Using a fixation method to preserve native CD marker expression prior to immunophenotyping, we identified a distinct population of "primed for recruitment" PMNs in healthy mouse and human blood that has high expression of adhesion and activation markers compared with the bulk resting-state PMNs. In response to acute tissue inflammation, primed PMNs (pPMNs) were rapidly depleted from the circulation and recruited to the tissue. One hour after acute peritoneal insult, pPMNs became the dominant PMN population in bone marrow (BM) and blood, returning to baseline levels with resolution of inflammation. PMN priming was induced by the granulopoietic factors granulocyte-macrophage-colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF). High levels of pPMNs were observed in neutropenic mice and in pediatric neutropenic patients who were resistant to infection, highlighting an important role of this population in innate immune function.


Assuntos
Neutrófilos/metabolismo , Adolescente , Adulto , Animais , Voluntários Saudáveis , Humanos , Camundongos , Adulto Jovem
11.
Cochrane Database Syst Rev ; 1: CD012405, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30629283

RESUMO

BACKGROUND: Dystonia is a painful and disabling disorder, characterised by painful, involuntary posturing of the affected body region(s). Deep brain stimulation is an intervention typically reserved for severe and drug-refractory cases, although uncertainty exists regarding its efficacy, safety, and tolerability. OBJECTIVES: To compare the efficacy, safety, and tolerability of deep brain stimulation (DBS) versus placebo, sham intervention, or best medical care, including botulinum toxin and resective or lesional surgery, in adults with dystonia. SEARCH METHODS: We identified studies by searching the CENTRAL, MEDLINE, Embase, three other databases, four clinical trial registries, four grey literature databases, and reference lists of included articles. We ran the last search of all elements of the search strategy, with no language restrictions, on 29 May 2018. SELECTION CRITERIA: Double-blind, parallel, randomised, controlled trials (RCTs) comparing DBS with sham stimulation, best medical care, or placebo in adults with dystonia. DATA COLLECTION AND ANALYSIS: Two independent review authors assessed records, selected included studies, extracted data onto a standardised (or prespecified) data extraction form, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third review author. We conducted meta-analyses using a random-effects model, to estimate pooled effects and corresponding 95% confidence intervals (95% CI). We assessed the quality of the evidence with GRADE methods. The primary efficacy outcome was symptom improvement on any validated symptomatic rating scale, and the primary safety outcome was adverse events. MAIN RESULTS: We included two RCTs, enrolling a total of 102 participants. Both trials evaluated the effect of DBS on the internal globus pallidus nucleus, and assessed outcomes after three and six months of stimulation. One of the studies included participants with generalised and segmental dystonia; the other included participants with focal (cervical) dystonia. We assessed both studies at high risk for performance and for-profit bias. One study was retrospectively registered with a clinical trial register, we judged the second at high risk of detection bias.Low-quality evidence suggests that DBS of the internal globus pallidus nucleus may improve overall cervical dystonia-related symptoms (mean difference (MD) 9.8 units, 95% CI 3.52 to 16.08 units; 1 RCT, 59 participants), cervical dystonia-related functional capacity (MD 3.8 units, 95% CI 1.41 to 6.19; 1 RCT, 61 participants), and mood at three months (MD 3.1 units, 95% CI 0.73 to 5.47; 1 RCT, 61 participants).Low-quality evidence suggests that In people with cervical dystonia, DBS may slightly improve the overall clinical status (MD 2.3 units, 95% CI 1.15 to 3.45; 1 RCT, 61 participants). We are uncertain whether DBS improves quality of life in cervical dystonia (MD 3 units, 95% CI -7.71 to 13.71; 1 RCT, 57 participants; very low-quality evidence), or emotional state (MD 2.4 units, 95% CI -6.2 to 11.00; 1 RCT, 56 participants; very low-quality evidence).Low-quality evidence suggests that DBS of the internal globus pallidus nucleus may improve generalised or segmental dystonia-related symptoms (MD 14.4 units, 95% CI 8.0 to 20.8; 1 RCT, 40 participants), overall clinical status (MD 3.5 units, 95% CI 2.33 to 4.67; 1 RCT, 37 participants), physical functioning-related quality of life (MD 6.3 units, 95% CI 1.06 to 11.54; 1 RCT, 33 participants), and overall dystonia-related functional capacity at three months (MD 3.1 units, 95% CI 1.71 to 4.48; 1 RCT, 39 participants). We are uncertain whether DBS improves physical functioning-related quality of life (MD 5.0 units, 95% CI -2.14 to 12.14, 1 RCT, 33 participants; very low-quality evidence), or mental health-related quality of life (MD -4.6 units, 95% CI -11.26 to 2.06; 1 RCT, 30 participants; very low-quality evidence) in generalised or segmental dystonia.We pooled outcomes related to safety and tolerability, since both trials used the same intervention and comparison. We found very low-quality evidence of inconclusive results for risk of adverse events (relative risk (RR) 1.58, 95% 0.98 to 2.54; 2 RCTs, 102 participants), and tolerability (RR 1.86, 95% CI 0.16 to 21.57; 2 RCTs,102 participants). AUTHORS' CONCLUSIONS: DBS of the internal globus pallidus nucleus may reduce symptom severity and improve functional capacity in adults with cervical, segmental or generalised moderate to severe dystonia (low-quality evidence), and may improve quality of life in adults with generalised or segmental dystonia (low-quality evidence). We are uncertain whether the procedure improves quality of life in cervical dystonia (very low-quality evidence). We are also uncertain about the safety and tolerability of the procedure in adults with either cervical and generalised, or segmental dystonia (very-low quality evidence).We could draw no conclusions for other populations with dystonia (i.e. children and adolescents, and adults with other types of dystonia), or for other DBS protocols (i.e. other target nuclei or stimulation paradigms). Further research is needed to establish the long-term efficacy and safety of DBS of the internal globus pallidus nucleus.


Assuntos
Estimulação Encefálica Profunda/métodos , Distúrbios Distônicos/terapia , Adolescente , Adulto , Fatores Etários , Criança , Globo Pálido , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Torcicolo/terapia
12.
J Magn Reson ; 296: 36-46, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30199791

RESUMO

An unshielded array of 87Rb atomic magnetometers, operating close to 1 MHz, is used to attenuate interference by 42-48 dB. A sensitivity of 15 fT/Hz to a local source of signal is retained. In addition, a 2D spectroscopic technique, in which the magnetometers are repeatedly pumped and data acquired between pump times, enables a synchronously generated signal to be distinguished from an interfering signal very close in frequency; the timing and signal mimics what would be observed in a magnetic resonance echo train. Combining the interference rejection and the 2D spectroscopy techniques, a 100 fT local signal is differentiated from a 20 pT interference signal operating only 1 Hz away. A phase-encoded reference signal is used to calibrate the magnetometers in real time in the presence of interference. Key to the strong interference rejection is the accurate calibration of the reference signal across the array, obtained through electron spin resonance measurements. This calibration is found to be sensitive to atomic polarization, RF pulse duration, and direction of the excitation. The experimental parameters required for an accurate and robust calibration are discussed.

13.
Cell Metab ; 25(5): 1063-1074.e3, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28434881

RESUMO

Intestinal dysbiosis contributes to obesity and insulin resistance, but intervening with antibiotics, prebiotics, or probiotics can be limited by specificity or sustained changes in microbial composition. Postbiotics include bacterial components such as lipopolysaccharides, which have been shown to promote insulin resistance during metabolic endotoxemia. We found that bacterial cell wall-derived muramyl dipeptide (MDP) is an insulin-sensitizing postbiotic that requires NOD2. Injecting MDP lowered adipose inflammation and reduced glucose intolerance in obese mice without causing weight loss or altering the composition of the microbiome. MDP reduced hepatic insulin resistance during obesity and low-level endotoxemia. NOD1-activating muropeptides worsened glucose tolerance. IRF4 distinguished opposing glycemic responses to different types of peptidoglycan and was required for MDP/NOD2-induced insulin sensitization and lower metabolic tissue inflammation during obesity and endotoxemia. IRF4 was dispensable for exacerbated glucose intolerance via NOD1. Mifamurtide, an MDP-based drug with orphan drug status, was an insulin sensitizer at clinically relevant doses in obese mice.


Assuntos
Acetilmuramil-Alanil-Isoglutamina/imunologia , Resistência à Insulina , Fatores Reguladores de Interferon/imunologia , Obesidade/complicações , Obesidade/microbiologia , Animais , Endotoxemia/complicações , Endotoxemia/imunologia , Endotoxemia/microbiologia , Inflamação/complicações , Inflamação/imunologia , Inflamação/microbiologia , Camundongos Endogâmicos C57BL , Camundongos Obesos , Microbiota , Proteína Adaptadora de Sinalização NOD1/imunologia , Proteína Adaptadora de Sinalização NOD2/imunologia , Obesidade/imunologia
14.
Cell Rep ; 18(10): 2415-2426, 2017 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-28273456

RESUMO

Insulin resistance is a chronic inflammatory condition accompanying obesity or high fat diets that leads to type 2 diabetes. It is hypothesized that lipids and gut bacterial compounds in particular contribute to metabolic inflammation by activating the immune system; however, the receptors detecting these "instigators" of inflammation remain largely undefined. Here, we show that circulating activators of NOD1, a receptor for bacterial peptidoglycan, increase with high fat feeding in mice, suggesting that NOD1 could be a critical sensor leading to metabolic inflammation. Hematopoietic depletion of NOD1 did not prevent weight gain but protected chimeric mice against diet-induced glucose and insulin intolerance. Mechanistically, while macrophage infiltration of adipose tissue persisted, notably these cells were less pro-inflammatory, had lower CXCL1 production, and consequently, lower neutrophil chemoattraction into the tissue. These findings reveal macrophage NOD1 as a cell-specific target to combat diet-induced inflammation past the step of macrophage infiltration, leading to insulin resistance.


Assuntos
Hematopoese , Inflamação/metabolismo , Inflamação/patologia , Resistência à Insulina , Proteína Adaptadora de Sinalização NOD1/metabolismo , Tecido Adiposo/patologia , Animais , Movimento Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Quimiocina CXCL1/metabolismo , Fatores Quimiotáticos/farmacologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Deleção de Genes , Glucose/metabolismo , Hematopoese/efeitos dos fármacos , Inflamação/complicações , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Knockout , Infiltração de Neutrófilos/efeitos dos fármacos , Obesidade/sangue , Obesidade/complicações , Obesidade/patologia
15.
J Exp Med ; 213(13): 2841-2850, 2016 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-27836928

RESUMO

The mammalian gastrointestinal tract hosts a diverse community of microbes including bacteria, fungi, protozoa, helminths, and viruses. Through coevolution, mammals and these microbes have developed a symbiosis that is sustained through the host's continuous sensing of microbial factors and the generation of a tolerant or pro-inflammatory response. While analyzing T cell-driven colitis in nonlittermate mouse strains, we serendipitously identified that a nongenetic transmissible factor dramatically increased disease susceptibility. We identified the protozoan Tritrichomonas muris as the disease-exacerbating element. Furthermore, experimental colonization with T. muris induced an elevated Th1 response in the cecum of naive wild-type mice and accelerated colitis in Rag1-/- mice after T cell transfer. Overall, we describe a novel cross-kingdom interaction within the murine gut that alters immune cell homeostasis and disease susceptibility. This example of unpredicted microbial priming of the immune response highlights the importance of studying trans-kingdom interactions and serves as a stark reminder of the importance of using littermate controls in all mouse research.


Assuntos
Colite/imunologia , Imunidade nas Mucosas , Mucosa Intestinal/imunologia , Linfócitos T/imunologia , Tritrichomonas/imunologia , Animais , Colite/genética , Colite/parasitologia , Colite/patologia , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/parasitologia , Suscetibilidade a Doenças/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/imunologia , Mucosa Intestinal/parasitologia , Mucosa Intestinal/patologia , Camundongos , Camundongos Knockout
16.
J Immunol ; 197(1): 345-55, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27206769

RESUMO

Loss of function in the NOD2 gene is associated with a higher risk of developing Crohn's disease (CD). CD is characterized by activation of T cells and activated T cells are involved in mucosal inflammation and mucosal damage. We found that acute T cell activation with anti-CD3 mAb induced stronger small intestinal mucosal damage in NOD2(-/-) mice compared with wild-type mice. This enhanced mucosal damage was characterized by loss of crypt architecture, increased epithelial cell apoptosis, delayed epithelial regeneration and an accumulation of inflammatory cytokines and Th17 cells in the small intestine. Partial microbiota depletion with antibiotics did not decrease mucosal damage 1 d after anti-CD3 mAb injection, but it significantly reduced crypt damage and inflammatory cytokine secretion in NOD2(-/-) mice 3 d after anti-CD3 mAb injection, indicating that microbial sensing by Nod2 was important to control mucosal damage and epithelial regeneration after anti-CD3 mAb injection. To determine which cells play a key role in microbial sensing and regulation of mucosal damage, we engineered mice carrying a cell-specific deletion of Nod2 in villin and Lyz2-expressing cells. T cell activation did not worsen crypt damage in mice carrying either cell-specific deletion of Nod2 compared with wild-type mice. However, increased numbers of apoptotic epithelial cells and higher expression of TNF-α and IL-22 were observed in mice carrying a deletion of Nod2 in Lyz2-expressing cells. Taken together, our results demonstrate that microbial sensing by Nod2 is an important mechanism to regulate small intestinal mucosal damage following acute T cell activation.


Assuntos
Doença de Crohn/genética , Mucosa Intestinal/imunologia , Intestino Delgado/patologia , Proteína Adaptadora de Sinalização NOD2/metabolismo , Linfócitos T/imunologia , Animais , Apoptose , Células Cultivadas , Citosol/metabolismo , Humanos , Interleucinas/metabolismo , Mucosa Intestinal/patologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação/genética , Proteína Adaptadora de Sinalização NOD2/genética , Regeneração , Fator de Necrose Tumoral alfa/metabolismo , Interleucina 22
17.
Sex Abuse ; 28(4): 340-59, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24872347

RESUMO

This study explored the prevalence of childhood trauma in a sample of male sexual offenders (N = 679) using the Adverse Childhood Experience (ACE) scale. Compared with males in the general population, sex offenders had more than 3 times the odds of child sexual abuse (CSA), nearly twice the odds of physical abuse, 13 times the odds of verbal abuse, and more than 4 times the odds of emotional neglect and coming from a broken home. Less than 16% endorsed zero ACEs and nearly half endorsed four or more. Multiple maltreatments often co-occurred with other types of household dysfunction, suggesting that many sex offenders were raised within a disordered social environment. Higher ACE scores were associated with higher risk scores. By enhancing our understanding of the frequency and correlates of early adverse experiences, we can better devise trauma-informed interventions that respond to the clinical needs of sex offender clients.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Vítimas de Crime/psicologia , Criminosos/psicologia , Delitos Sexuais/psicologia , Criança , Abuso Sexual na Infância/psicologia , Humanos , Masculino , Prevalência , Fatores de Risco
18.
PLoS One ; 10(5): e0127059, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25993256

RESUMO

A detailed understanding of the population dynamics of many amphibian species is lacking despite concerns about declining amphibian biodiversity and abundance. This paper explores temporal patterns of occupancy and underlying extinction and colonization dynamics in a regionally imperiled amphibian species, the Northern leopard frog (Lithobates pipiens) in Alberta. Our study contributes to elucidating regional occupancy dynamics at northern latitudes, where climate extremes likely have a profound effect on seasonal occupancy. The primary advantage of our study is its wide geographic scale (60,000 km2) and the use of repeat visual surveys each spring and summer from 2009-2013. We find that occupancy varied more dramatically between seasons than years, with low spring and higher summer occupancy. Between spring and summer, colonization was high and extinction low; inversely, colonization was low and extinction high over the winter. The dynamics of extinction and colonization are complex, making conservation management challenging. Our results reveal that Northern leopard frog occupancy was constant over the last five years and thus there is no evidence of decline or recovery within our study area. Changes to equilibrium occupancy are most sensitive to increasing colonization in the spring or declining extinction in the summer. Therefore, conservation and management efforts should target actions that are likely to increase spring colonization; this could be achieved through translocations or improving the quality or access to breeding habitat. Because summer occupancy is already high, it may be difficult to improve further. Nevertheless, summer extinction could be reduced by predator control, increasing water quality or hydroperiod of wetlands, or increasing the quality or quantity of summer habitat.


Assuntos
Anfíbios , Ecossistema , Estações do Ano , Alberta , Animais , Modelos Teóricos , Dinâmica Populacional , Rana pipiens
19.
Cell Metab ; 21(4): 527-42, 2015 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-25863246

RESUMO

Obesity has reached epidemic proportions, but little is known about its influence on the intestinal immune system. Here we show that the gut immune system is altered during high-fat diet (HFD) feeding and is a functional regulator of obesity-related insulin resistance (IR) that can be exploited therapeutically. Obesity induces a chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations. Reduction of the gut immune system, using beta7 integrin-deficient mice (Beta7(null)), decreases HFD-induced IR. Treatment of wild-type HFD C57BL/6 mice with the local gut anti-inflammatory, 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters. These beneficial effects are dependent on adaptive and gut immunity and are associated with reduced gut permeability and endotoxemia, decreased visceral adipose tissue inflammation, and improved antigen-specific tolerance to luminal antigens. Thus, the mucosal immune system affects multiple pathways associated with systemic IR and represents a novel therapeutic target in this disease.


Assuntos
Anti-Inflamatórios/farmacologia , Trato Gastrointestinal/imunologia , Imunidade nas Mucosas/imunologia , Resistência à Insulina/imunologia , Obesidade/imunologia , Animais , Western Blotting , Citocinas/sangue , Dieta Hiperlipídica/efeitos adversos , Citometria de Fluxo , Trato Gastrointestinal/efeitos dos fármacos , Técnicas Histológicas , Imuno-Histoquímica , Cadeias beta de Integrinas/metabolismo , Mesalamina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Mucosa/citologia , Mucosa/imunologia
20.
Sex Abuse ; 27(3): 258-83, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25210107

RESUMO

This study explored the prevalence of early trauma in a sample of U.S. female sexual offenders (N = 47) using the Adverse Childhood Experiences (ACE) scale. Compared with females in the general population, sex offenders had more than three times the odds of child sexual abuse, four times the odds of verbal abuse, and more than three times the odds of emotional neglect and having an incarcerated family member. Half of the female sex offenders had been sexually abused as a child. Only 20% endorsed zero adverse childhood experiences (compared with 35% of the general female population) and 41% endorsed four or more (compared with 15% of the general female population). Higher ACE scores were associated with having younger victims. Multiple maltreatments often co-occurred in households with other types of dysfunction, suggesting that many female sex offenders were raised within a disordered social environment by adults with problems of their own who were ill-equipped to protect their daughters from harm. By enhancing our understanding of the frequency and correlates of early adverse experiences, we can better devise trauma-informed interventions that respond to the clinical needs of female sex offender clients.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Abuso Sexual na Infância/estatística & dados numéricos , Vítimas de Crime/estatística & dados numéricos , Criminosos/estatística & dados numéricos , Delitos Sexuais/estatística & dados numéricos , Mulheres , Adolescente , Adulto , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Adultos Sobreviventes de Eventos Adversos na Infância/psicologia , Adultos Sobreviventes de Eventos Adversos na Infância/estatística & dados numéricos , Estudos de Casos e Controles , Abuso Sexual na Infância/psicologia , Vítimas de Crime/psicologia , Criminosos/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Delitos Sexuais/psicologia , Estados Unidos , Mulheres/psicologia , Adulto Jovem
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