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1.
Environ Microbiol ; 21(12): 4822-4835, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31631506

RESUMO

Liberibacter asiaticus is the prevalent causative pathogen of Huanglongbing or citrus greening disease, which has resulted in a devastating crisis in the citrus industry. A thorough understanding of this pathogen's physiology and mechanisms to control cell survival is critical in the identification of therapeutic targets. YbeY is a highly conserved bacterial RNase that has been implicated in multiple roles. In this study, we evaluated the biochemical characteristics of the L. asiaticus YbeY (CLIBASIA_01560) and assessed its potential as a target for antimicrobials. YbeYLas was characterized as an endoribonuclease with activity on 3' and 5' termini of 16S and 23S rRNAs, and the capacity to suppress the E. coli ΔybeY phenotype. We predicted the YbeYLas protein:ligand interface and subsequently identified a flavone compound, luteolin, as a selective inhibitor. Site-directed mutagenesis was subsequently used to identify key residues involved in the catalytic activity of YbeYLas. Further evaluation of naturally occurring flavonoids in citrus trees indicated that both flavones and flavonols had potent inhibitory effects on YbeYLas . Luteolin was subsequently examined for efficacy against L. asiaticus in Huanglongbing-infected citrus trees, where a significant reduction in L. asiaticus gene expression was observed.


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/química , Flavonoides/química , Rhizobiaceae/enzimologia , Ribonucleases/antagonistas & inibidores , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Citrus/microbiologia , Inibidores Enzimáticos/metabolismo , Flavonoides/metabolismo , Doenças das Plantas/microbiologia , Rhizobiaceae/química , Rhizobiaceae/genética , Ribonucleases/química , Ribonucleases/genética , Ribonucleases/metabolismo
2.
Appl Environ Microbiol ; 85(4)2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30552192

RESUMO

In Liberibacter asiaticus, PrbP is an important transcriptional accessory protein that regulates gene expression through interactions with the RNA polymerase ß-subunit and a specific sequence on the promoter region. The constitutive expression of prbP observed upon chemical inactivation of PrbP-DNA interactions in vivo indicated that the expression of prbP was not autoregulated at the level of transcription. This observation suggested that a modulatory mechanism via protein-protein interactions may be involved. In silico genome association analysis identified FerR (CLIBASIA_01505), a putative ferredoxin-like protein, as a PrbP-interacting protein. Using a bacterial two-hybrid system and immunoprecipitation assays, interactions between PrbP and FerR were confirmed. In vitro transcription assays were used to show that FerR can increase the activity of PrbP by 16-fold when present in the PrbP-RNA polymerase reaction mixture. The FerR protein-protein interaction surface was predicted by structural modeling and followed by site-directed mutagenesis. Amino acids V20, V23, and C40 were identified as the most important residues in FerR involved in the modulation of PrbP activity in vitro The regulatory mechanism of FerR abundance was examined at the transcription level. In contrast to prbP of L. asiaticus (prbPLas), mRNA levels of ferR of L. asiaticus (ferRLas) are induced by an increase in osmotic pressure. The results of this study revealed that the activity of the transcriptional activator PrbPLas is modulated via interactions with FerRLas The induction of ferRLas expression by osmolarity provides insight into the mechanisms of adjusting gene expression in response to host environmental signals in L. asiaticusIMPORTANCE The rapid spread and aggressive progression of huanglongbing (HLB) in the major citrus-producing areas have raised global recognition of and vigilance to this disease. As a result, the causative agent, Liberibacter asiaticus, has been investigated from various perspectives. However, gene expression regulatory mechanisms that are important for the survival and persistence of this intracellular pathogen remain largely unexplored. PrbP is a transcriptional accessory protein important for L. asiaticus survival in the plant host. In this study, we investigated the interactions between PrbP in L. asiaticus (PrbPLas) and a ferredoxin-like protein (FerR) in L. asiaticus, FerRLas We show that the presence of FerR stabilizes and augments the activity of PrbPLas In addition, we demonstrate that the expression of ferR is induced by increases in osmolarity in Liberibacter crescens Altogether, these results suggest that FerRLas and PrbPLas may play important roles in the regulation of gene expression in response to changing environmental signals during L. asiaticus infection in the citrus host.


Assuntos
Ferredoxinas/genética , Ferredoxinas/metabolismo , Rhizobiaceae/genética , Rhizobiaceae/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Citrus/microbiologia , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Interações Hospedeiro-Patógeno , Modelos Moleculares , Pressão Osmótica , Doenças das Plantas/microbiologia , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas
4.
J Clin Endocrinol Metab ; 109(8): 1984-1995, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38373265

RESUMO

CONTEXT: Omnipod DASH Insulin Management System is a tubeless insulin pump that overcomes the physical inconveniences of conventional tubed insulin pump therapy (IPT). OBJECTIVE: We compared treatment satisfaction with Omnipod DASH System to usual care (multiple daily injections [MDIs] or tubed IPT) in adults with type 1 diabetes using self-monitoring blood glucose (SMBG). METHODS: Adults with type 1 diabetes on MDI (n = 40) or IPT (n = 25) from 4 diabetes centers in Australia were randomly assigned in a 1:1 nonblinded manner to Omnipod DASH System (Omnipod group) or continue usual care (Usual Care group) for 12 weeks, followed by a further 12-week extension during which all participants used the device. The primary outcome was treatment satisfaction assessed by change in Diabetes Technology Questionnaire "current" (ΔDTQ-current) score at 12 weeks (study end). Secondary outcomes included ΔDTQ-current following extension and other participant-reported outcomes (PROs) measuring quality of life, burden of disease treatment, and glycemic and device-related outcomes at 12 weeks (study end) and 24 weeks (end extension). RESULTS: Treatment satisfaction improved more in the Omnipod group vs the Usual Care group (ΔDTQ-current score of 16.4 [21.2] vs 0.0 [12.8]; P < .001) at study end. Significantly greater improvements in other PROs and glycated hemoglobin A1c were also observed. Improvements in DTQ-current and other PROs comparing study end and end extension were similar. While percentage in time in range change from baseline did not differ at study end (-2.0 [12.7] %), it was significantly greater at end extension (5.6 [10.9] %; P = .016). CONCLUSION: The Omnipod DASH System resulted in greater treatment satisfaction at 12 weeks in adults with type 1 diabetes using SMBG that was sustained after 24 weeks of device use without compromising sleep quality and fear of hypoglycemia. Improvements in glycemia were also observed.


Assuntos
Automonitorização da Glicemia , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Sistemas de Infusão de Insulina , Insulina , Satisfação do Paciente , Qualidade de Vida , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/psicologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Automonitorização da Glicemia/métodos , Automonitorização da Glicemia/instrumentação , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Glicemia/análise , Hemoglobinas Glicadas/análise , Resultado do Tratamento , Austrália
5.
Diabetes Res Clin Pract ; 208: 111123, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309532

RESUMO

AIMS: Understanding the lived experience of using a tubeless insulin pump and how this differs compared to usual care (tubed insulin pump therapy (IPT) vs multiple daily injections (MDI)). METHODS: Interviews were conducted after 12-weeks of using the Omnipod DASH Insulin Management System (Insulet, Acton, MA) and analysed using thematic analysis. RESULTS: Fifty-eight adults (35 female; mean age 42;SD 13 years; 35 previous MDI) were interviewed. Most (84 %) wanted to continue using the device. Experiences fit two themes: 1. Taking back control of my diabetes: many previous MDI users perceived improved glycaemic control, explained by more "nuanced" control, with some reporting positive effects during exercise and sleep. Many previous MDI and IPT users endorsed positive experiences in concealing or disclosing their diabetes to others. However, some previous MDI users reported negative psychosocial experiences due to feeling continuously "attached" to their diabetes. 2. Barriers and facilitators of device acceptability: both MDI and IPT users cited wearability, alarms and the financial cost impacted their choice to continue device use. IPT users reported positive wearability experiences. CONCLUSIONS: The tubeless pump improved diabetes management perceptions for both MDI and tubed pump users. However, participants' prior glucose management affected perceptions of its advantages and disadvantages.


Assuntos
Diabetes Mellitus Tipo 1 , Adulto , Humanos , Feminino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/psicologia , Hipoglicemiantes/uso terapêutico , Austrália , Insulina/uso terapêutico , Injeções , Sistemas de Infusão de Insulina , Glicemia
7.
Pilot Feasibility Stud ; 9(1): 171, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814352

RESUMO

BACKGROUND: Insulin pump therapy (IPT) improves glucose control in people with type 1 diabetes (T1D) compared with multiple daily injections (MDI). However, their size, the tethered insulin infusion set, intrusiveness when operating the device and the need to disconnect during showering limit their acceptance to many who may benefit. The Omnipod DASH® Insulin Management System is a small waterproof tubeless device which is wirelessly controlled by a handheld device which may be an acceptable alternative. However, there are no randomised controlled trials focusing on the impact on user perceptions of tubeless insulin pump therapy. This pilot study aims to assess study feasibility and acceptability of patch pump therapy compared with usual care in adults with T1D in Australia to inform power calculations and progression to a large-scale multi-site randomised controlled study. METHODS: A pilot multi-site parallel randomised controlled study will be conducted in sixty-four adults with T1D who are managed on MDI or IPT and self-monitoring with finger-stick blood glucose from four specialist diabetes centres in Victoria, Australia. Following carbohydrate counting education, participants will be randomised to use Omnipod DASH® System (Omnipod group) or continue usual care (usual care group) for 12 weeks, followed by a 12-week extension phase where all participants will use Omnipod DASH® System. The primary outcome measure is feasibility determined by study completion rates with a threshold of 0.80. Acceptability of the intervention (Omnipod DASH® System) will be assessed by the difference in Diabetes Technology Questionnaire 'current' (DTQ-current) score at 12 weeks post-randomisation compared to baseline. Secondary outcomes will include other measures of user acceptance, process outcomes, resource outcomes, participant-centred outcomes, healthcare professional perceptions and glycaemic outcomes. DISCUSSION: This pilot study will provide insights regarding the feasibility of the study design and the first data regarding user acceptance of insulin patch pump technology in Australian T1D adults. We anticipate that this study will provide information informing the design of a larger study evaluating the impact of patch pumps on subjective outcomes that are of significance to the person living with T1D. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( https://anzctr.org.au/ ) ACTRN12621001195842 (8th September 2021). Please refer to Additional file 1: Appendix 1 for full details.

9.
Front Immunol ; 13: 899413, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757772

RESUMO

L. johnsonii N6.2 releases nano-sized vesicles (NVs) with distinct protein and lipid contents. We hypothesized that these NVs play a central role in the delivery of bioactive molecules that may act as mechanistic effectors in immune modulation. In this report, we observed that addition of NVs to the human pancreatic cell line ßlox5 reduced cytokine-induced apoptosis. Through RNAseq analyses, increased expression of CYP1A1, CYP1B1, AHRR, and TIPARP genes in the aryl hydrocarbon receptor (AHR) pathways were found to be significantly induced in presence of NVs. AHR nuclear translocation was confirmed by confocal microscopy. The role of NVs on beta cell function was further evaluated using primary human pancreatic islets. It was found that NVs significantly increased insulin secretion in presence of high glucose concentrations. These increases positively correlated with increased GLUT6 and SREBF1 mRNA and coincided with reduced oxidative stress markers. Furthermore, incubation of NVs with THP-1 macrophages promoted the M2 tolerogenic phenotype through STAT3 activation, expression of AHR-dependent genes and secretion of IL10. Altogether, our findings indicate that bacterial NVs have the potential to modulate glucose homeostasis in the host by directly affecting insulin secretion by islets and through the induction of a tolerogenic immune phenotype.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Interleucina-10 , Lactobacillus johnsonii , Receptores de Hidrocarboneto Arílico , Apoptose/imunologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/imunologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Glucose/metabolismo , Humanos , Interleucina-10/imunologia , Interleucina-10/metabolismo , Lactobacillus johnsonii/genética , Lactobacillus johnsonii/imunologia , Lactobacillus johnsonii/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/imunologia , Receptores de Hidrocarboneto Arílico/metabolismo
10.
Lancet Oncol ; 16(6): 616, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26065601

Assuntos
Morte , Humanos , Reino Unido
11.
Psychophysiology ; 58(1): e13694, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33040361

RESUMO

Prominent theory suggests that factor one psychopathic traits may develop from increased input from hormones in the hypothalamic pituitary gonadal axis (HPG; i.e., testosterone) and decreased input from the hypothalamic pituitary adrenal axis (HPA; i.e., cortisol). Although there are extensive findings connecting low cortisol to psychopathy, less support has emerged for high levels of testosterone. This study examined whether incorporating the HPG hormone, estradiol, into this model would reveal relationships in line with theory: high levels of estradiol and testosterone in combination with low levels of cortisol would inform psychopathic traits. Baseline and reactive hormone levels were measured and compared to Psychopathy Checklist-Youth Version (PCL-YV) interviews among 66 male justice-involved youth (M age = 15.73) in a Southeastern juvenile detention center. The primary findings of this study were relationships between interacting HPA and HPG axis hormones with facet one and facet two psychopathic traits. Specifically, psychopathy total scores, interpersonal traits, and affective traits related to estradiol and testosterone reactivity, in that psychopathy scores were more likely with decreases in hormone reactivity (i.e., change in hormone level) following a stressor. Moreover, affective traits related to reactivity in all three hormones. These findings support inclusion of estradiol in neurobiological models of psychopathy and consideration of the individual components of psychopathy. This study adds to the growing body of research supporting interactions between variations in functioning of the HPA and HPG axes in relation to psychopathy.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Transtorno da Conduta/metabolismo , Transtorno da Conduta/fisiopatologia , Estradiol/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Delinquência Juvenil , Adolescente , Sintomas Afetivos/etiologia , Sintomas Afetivos/metabolismo , Sintomas Afetivos/fisiopatologia , Transtorno da Conduta/complicações , Humanos , Hidrocortisona/metabolismo , Relações Interpessoais , Masculino , Saliva/metabolismo , Testosterona/metabolismo
12.
Front Immunol ; 12: 723433, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531870

RESUMO

The ability of bacterial extracellular vesicles (EV) to transport biological molecules has increased the research to determine their potential as therapeutic agents. In this study, Lactobacillus johnsonii N6.2-derived nanovesicles (NV) were characterized to identify components that may serve as biomarkers in host-microbe interactions. Comparative proteomic and lipidomic analyses of L. johnsonii N6.2 NV and cell membrane (CM) were performed. The lipidomic profiles indicated that both fractions contained similar lipids, however, significant differences were observed in several classes. LC-MS/MS proteomic analysis indicated that NV contained several unique and differentially expressed proteins when compared to the CM. Analysis of Gene Ontology (GO) terms, based on cellular component, showed significant enrichment of proteins in the cytoplasm/intracellular space category for the NV fraction. Based on these results, the proteins T285_RS00825 (named Sdp), Eno3 and LexA were selected for studies of localization and as potential biomarkers for host-microbe interactions. Immunogold staining, followed by scanning and transmission electron microscopy (SEM and TEM, respectively), revealed that Sdp was preferentially localized along the cell wall/membrane, and on NV-like structures surrounding the bacteria. These results were confirmed using immunofluorescence staining in Caco-2 cells incubated with NV. Consequently, we evaluated the potential for NV surface-exposed proteins to generate an immune response in the host. Plasma from individuals administered L. johnsonii N6.2 showed that IgA and IgG antibodies were generated against NV and Sdp domains in vivo. Altogether, these results show that L. johnsonii N6.2 NV have the potential to mediate host interactions through immune modulation.


Assuntos
Biomarcadores/análise , Vesículas Extracelulares/química , Interações entre Hospedeiro e Microrganismos/imunologia , Lactobacillus johnsonii/imunologia , Nanoestruturas/química , Células CACO-2 , Cromatografia Líquida , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Lactobacillus johnsonii/química , Probióticos , Espectrometria de Massas em Tandem
13.
J Psychiatr Ment Health Nurs ; 28(1): 56-71, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31957217

RESUMO

WHAT IS KNOWN ABOUT THE SUBJECT?: People experiencing mental distress have a high rate of contact with police in community crisis events. Police use a continuum of responses when managing situations involving agitation, aggression and behavioural problems. People experiencing mental distress have been subjected to Tasers as part of the police response. Following a number of deaths and numerous reports of injuries, concerns have been raised about the safety of Tasers. WHAT THIS PAPER ADDS?: Police use of Tasers in mental health crises is relatively common. Tasers are used in a range of settings including public places, private residences and healthcare facilities. People experiencing mental distress may be subjected to more use of Tasers than the general population. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health professionals need to work with police towards greater understanding of the needs of people experiencing mental distress and to promote the use of non-coercive interventions in mental health crisis events. Mental health researchers need to explore the qualitative experiences of people who are Tasered, to provide an evidence base for Taser use with people experiencing mental distress. ABSTRACT: Introduction Conducted electrical weapons, or "Tasers," are currently used by over 15,000 law enforcement and military agencies worldwide. There are concerns regarding the effectiveness, potential for harm and overuse with people experiencing mental distress. Aim To explore the literature about police use of Tasers with people experiencing mental distress. Method An integrative review was undertaken, and qualitative and quantitative analytical approaches were used. Results Thirty-one studies were included. Of all recorded usage, overall prevalence of Taser use on people experiencing mental distress was 28%. This population appears to experience higher Taser usage than the general population. Discussion There are substantial gaps in the research literature particularly with respect to the decision-making processes involved in deploying Tasers on this population and the physical and psychological consequences of Taser use in this context. Implications for practice Police use of Tasers in mental health crises is relatively common and occurs in a variety of environments including mental health settings. Mental health professionals need to work with police towards greater understanding of the needs of people with mental illness and to promote the use of non-coercive interventions in mental health crisis events.


Assuntos
Transtornos Mentais , Humanos , Saúde Mental , Polícia
14.
Front Microbiol ; 12: 656889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936012

RESUMO

Feeding preterm infants mother's own milk (MOM) lowers rates of sepsis, decreases necrotizing enterocolitis, and shortens hospital stay. In the absence of freshly expressed MOM, frozen MOM (FMOM) is provided. When MOM is unavailable, preterm infants are often fed pasteurized donor human milk (DHM), rendering it devoid of beneficial bacteria. We have previously reported that when MOM is inoculated into DHM to restore the live microbiota [restored milk (RM)], a similar microbial diversity to MOM can be achieved. Yet, it is unknown if a similar diversity to MOM can be obtained when FMOM is inoculated into DHM. The goal of this study was to determine whether a similar microbial composition to MOM could be obtained when FMOM is used to personalize DHM. To this end, a fresh sample of MOM was obtained and divided into fresh and frozen fractions. MOM and FMOM were inoculated into DHM at different dilutions: MOM/FMOM 10% (RM/FRM10) and MOM/FMOM 30% (RM/FRM30) and incubated at 37°C. At different timepoints, culture-dependent and culture-independent techniques were performed. Similar microbiota expansion and alpha diversity were observed in MOM, RM10, and RM30 whether fresh or frozen milk was used as the inoculum. To evaluate if microbial expansion would result in an abnormal activation on the innate immune system, Caco-2 epithelial cells were exposed to RM/FRM to compare interleukin 8 levels with Caco-2 cells exposed to MOM or DHM. It was found that RM samples did not elicit a significant increase in IL-8 levels when compared to MOM or FMOM. These results suggest that FMOM can be used to inoculate DHM if fresh MOM is unavailable or limited in supply, allowing both fresh MOM and FMOM to be viable options in a microbial restoration strategy.

15.
Cognition ; 198: 104200, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32004933

RESUMO

Such is the consistency by which performance on measures of short-term memory (STM) increase with age that developmental increases in STM capacity are largely accepted as fact. However, our analysis of a robust but almost ignored finding - that span for digit sequences (the traditional measure of STM) increases at a far greater rate than span for other verbal material - fundamentally undermines the assumption that increased performance in STM tasks is underpinned by developmental increases in capacity. We show that this digit superiority with age effect is explained by the relatively greater linguistic exposure to random sequences of digits versus other stimuli such as words. A simple associative learning process that learns incrementally from exposure to language accounts for the effect, without any need to invoke an STM mechanism, much less one that increases in capacity with age. By extension, using corpus data directed at 2-3 year old children, 4-6 year old children, and adults, we show that age-related performance increases with other types of verbal material are equally driven by the same basic associative learning process operating on the expanding exposure to language experienced by the child. Our results question the idea that tests such as digit span are measuring a dedicated system for the temporary maintenance and manipulation of verbal material, and as such have implications for our understanding of those aspects of typical and atypical development that are usually accounted for with respect to the operation of such a system.


Assuntos
Idioma , Memória de Curto Prazo , Adulto , Criança , Pré-Escolar , Humanos , Aprendizagem
16.
Front Microbiol ; 8: 1470, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824595

RESUMO

The American Academy of Pediatrics recommends that extremely preterm infants receive mother's own milk (MOM) when available or pasteurized donor breast milk (DBM) when MOM is unavailable. The goal of this study was to determine whether DBM could be inoculated with MOM from mothers of preterm infants to restore the live microbiota (RM). Culture dependent and culture independent methods were used to analyze the fluctuations in the overall population and microbiome, respectively, of DBM, MOM, and RM samples over time. Using MOM at time = 0 (T0) as the target for the restoration process, this level was reached in the 10% (RM-10) and 30% (RM-30) mixtures after 4 h of incubation at 37°C, whereas, the larger dilutions of 1% (RM-1) and 5% (RM-5) after 8 h. The diversity indexes were similar between MOM and DBM samples, however, different genera were prevalent in each group. Interestingly, 40% of the bacterial families were able to expand in DBM after 4 h of incubation indicating that a large percentage of the bacterial load present in MOM can grow when transferred to DBM, however, no core microbiome was identified. In summary, the microbiome analyses indicated that each mother has a unique microbiota and that live microbial reestablishment of DBM may provide these microbes to individual mothers' infants. The agreement between the results obtained from the viable bacterial counts and the microbiome analyses indicate that DBM incubated with 10-30% v/v of the MOM for 4 h is a reasonable restoration strategy.

17.
Front Immunol ; 8: 655, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28659913

RESUMO

Lactobacillus johnsonii N6.2 mitigates the onset of type 1 diabetes (T1D) in biobreeding diabetes-prone rats, in part, through changes in kynurenine:tryptophan (K:T) ratios. The goal of this pilot study was to determine the safety, tolerance, and general immunological response of L. johnsonii N6.2 in healthy subjects. A double-blind, randomized clinical trial in 42 healthy individuals with no known risk factors for T1D was undertaken to evaluate subject responses to the consumption of L. johnsonii N6.2. Participants received 1 capsule/day containing 108 colony-forming units of L. johnsonii N6.2 or placebo for 8 weeks. Comprehensive metabolic panel (CMP), leukocyte subpopulations by complete blood count (CBC) and flow cytometry, serum cytokines, and relevant metabolites in the indoleamine-2,3-dioxygenase pathway were assessed. L. johnsonii N6.2 survival and intestinal microbiota was analyzed. Daily and weekly questionnaires were assessed for potential effects of probiotic treatment on general wellness. The administration of L. johnsonii N6.2 did not modify the CMP or CBC of participants suggesting general safety. In fact, L. johnsonii N6.2 administration significantly decreased the occurrence of abdominal pain, indigestion, and cephalic syndromes. As predicted, increased serum tryptophan levels increased resulting in a decreased K:T ratio was observed in the L. johnsonii N6.2 group. Interestingly, immunophenotyping assays revealed that monocytes and natural killer cell numbers were increased significantly after washout (12 weeks). Moreover, an increase of circulating effector Th1 cells (CD45RO+CD183+CD196-) and cytotoxic CD8+ T cells subset was observed in the L. johnsonii N6.2 group. Consumption of L. johnsonii N6.2 is well tolerated in adult control subjects, demonstrates systemic impacts on innate and adaptive immune populations, and results in a decreased K:T ratio. These data provide support for the safety and feasibility of using L. johnsonii N6.2 in prevention trials in subjects at risk for T1D. TRIAL REGISTRATION: This trial was registered at http://clinicaltrials.gov as NCT02349360.

18.
Diabetes Res Clin Pract ; 116: 159-64, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27321331

RESUMO

AIMS: To evaluate the achievement of HbA1c targets in patients with type 2 diabetes mellitus in specialist practice. METHODS: This audit was undertaken by members of the S4S Diabetes Informatics Group (DINGO), a consortium of Australian endocrinologists in private practice who contribute de-identified data from their electronic medical record, Audit 4 (Software 4 Specialists, S4S, Australia & New Zealand) for audit purposes. Data from patients with type 2 diabetes was extracted. Inclusion criteria were: initial age<70years, baseline HbA1c>7% (53mmol/mol), with at least another HbA1c recorded in the next 2years, and a minimum of 2years follow-up. Data was analysed using a linear mixed effects model. RESULTS: Of the 4796 patients in the dataset with type 2 diabetes mellitus, 1379 patients fulfilled inclusion criteria. The median age at initial consultation was 57 (49-64)years. The median baseline HbA1c was 8.7 (7.8-9.8)% (72mmol/mol). There was a 1.0% reduction in HbA1c to 7.7 (7.1-8.6)% (61mmol/mol) (p<0.0001) in the first 3-6months following referral, after which there were no further changes. The initial reduction was maintained with minimal loss of control at 4years. By 3-6months, 24% of patients achieved the target HbA1c. CONCLUSIONS: Referral of patients with type 2 diabetes to an endocrinologist reduces HbA1c, and the effect is sustained over the medium term; however only a minority of patients reach targets.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/análise , Auditoria Médica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Personal Disord ; 7(3): 269-79, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27064713

RESUMO

Psychopathy is often associated with heightened intelligence in the eyes of clinicians and laypersons despite mixed research support for this possibility. We adopted a fine-grained approach to studying the relations among psychopathy and multiple indices of intelligence, including both cognitively based intelligence (CBI) and emotional intelligence (EI), in a large sample of undergraduates (N = 1,257, 70% female, 82% Caucasian). We found no clear support for marked associations between psychopathy and CB I measures, with the magnitudes of these relations being small. With the exception of the dimensions of Fearless Dominance (FD) and Coldheartedness (C), psychopathy dimensions were negatively associated with (EI). In contrast, we found some support for the hypothesis that intelligence served as a protective factor against antisocial behavior among individuals with high levels of psychopathy. On balance, our findings show weak relations between psychopathy and intelligence, suggesting that the link between them may be less robust than theoretical models portray, at least among undergraduates. (PsycINFO Database Record


Assuntos
Transtorno da Personalidade Antissocial/fisiopatologia , Inteligência Emocional/fisiologia , Inteligência/fisiologia , Adulto , Feminino , Humanos , Masculino , Fatores de Proteção , Adulto Jovem
20.
J Appl Anim Welf Sci ; 17(4): 322-39, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24673506

RESUMO

Bull breeds are commonly kept as companion animals, but the pit bull terrier is restricted by breed-specific legislation (BSL) in parts of the United States and throughout the United Kingdom. Shelter workers must decide which breed(s) a dog is. This decision may influence the dog's fate, particularly in places with BSL. In this study, shelter workers in the United States and United Kingdom were shown pictures of 20 dogs and were asked what breed each dog was, how they determined each dog's breed, whether each dog was a pit bull, and what they expected the fate of each dog to be. There was much variation in responses both between and within the United States and United Kingdom. UK participants frequently labeled dogs commonly considered by U.S. participants to be pit bulls as Staffordshire bull terriers. UK participants were more likely to say their shelters would euthanize dogs deemed to be pit bulls. Most participants noted using dogs' physical features to determine breed, and 41% affected by BSL indicated they would knowingly mislabel a dog of a restricted breed, presumably to increase the dog's adoption chances.


Assuntos
Bem-Estar do Animal/estatística & dados numéricos , Cães , Adolescente , Adulto , Bem-Estar do Animal/legislação & jurisprudência , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Especificidade da Espécie , Reino Unido , Estados Unidos , Adulto Jovem
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