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1.
Sci Adv ; 6(31)2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32937596

RESUMO

Microtubules display dynamic turnover during cell migration, leading to cell contractility and focal adhesion maturation regulated by Rho guanosine triphosphatase activity. This interplay between microtubules and actomyosin is mediated by guanine nucleotide exchange factor (GEF)-H1 released after microtubule depolymerization or microtubule disconnection from focal adhesions. However, how GEF-H1 activates Rho upon microtubule disassembly remains elusive. Here, we found that BNIP-2, a BCH domain-containing protein that binds both RhoA and GEF-H1 and traffics with kinesin-1 on microtubules, is important for GEF-H1-driven RhoA activation upon microtubule disassembly. Depletion of BNIP-2 in MDA-MB-231 breast cancer cells decreases RhoA activity and promotes cell migration. Upon nocodazole-induced microtubule disassembly, the interaction between BNIP-2 and GEF-H1 increases, while knockdown of BNIP-2 reduces RhoA activation and cell rounding via uncoupling RhoA-GEF-H1 interaction. Together, these findings revealed that BNIP-2 couples microtubules and focal adhesions via scaffolding GEF-H1 and RhoA, fine-tuning RhoA activity and cell migration.

2.
Sci Adv ; 6(31): eaaz1534, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32789168

RESUMO

Microtubules display dynamic turnover during cell migration, leading to cell contractility and focal adhesion maturation regulated by Rho guanosine triphosphatase activity. This interplay between microtubules and actomyosin is mediated by guanine nucleotide exchange factor (GEF)-H1 released after microtubule depolymerization or microtubule disconnection from focal adhesions. However, how GEF-H1 activates Rho upon microtubule disassembly remains elusive. Here, we found that BNIP-2, a BCH domain-containing protein that binds both RhoA and GEF-H1 and traffics with kinesin-1 on microtubules, is important for GEF-H1-driven RhoA activation upon microtubule disassembly. Depletion of BNIP-2 in MDA-MB-231 breast cancer cells decreases RhoA activity and promotes cell migration. Upon nocodazole-induced microtubule disassembly, the interaction between BNIP-2 and GEF-H1 increases, while knockdown of BNIP-2 reduces RhoA activation and cell rounding via uncoupling RhoA-GEF-H1 interaction. Together, these findings revealed that BNIP-2 couples microtubules and focal adhesions via scaffolding GEF-H1 and RhoA, fine-tuning RhoA activity and cell migration.

3.
Hepatology ; 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32780526

RESUMO

BACKGROUND: We conducted haplotype analysis of complete hepatitis B virus (HBV) genomes following deep sequencing from 368 patients across multiple phases of chronic Hepatitis B (CHB) infection from 4 major genotypes (A to D), analysing 4110 haplotypes to identify viral variants associated with treatment outcome and disease progression. RESULTS: Between 18.2% and 41.8% of nucleotides and between 5.9% and 34.3% of amino acids were 100% conserved in all genotypes and phases examined, depending on the region analysed. HBeAg loss by week 192 was associated with different haplotype populations at baseline. Haplotype populations differed across the HBV genome and CHB history, this being most pronounced in the precore/core gene. Mean number of haplotypes (frequency) per patient was higher in immune active HBeAg-positive chronic hepatitis Phase II (11.8) and HBeAg-negative chronic hepatitis Phase IV (16.2) compared to subjects in the "immune tolerant" HBeAg-positive chronic infection Phase I (4.3, p<0.0001). Haplotype frequency was lowest in genotype B (6.2, p<0.0001) compared to the other genotypes (A = 11.8, C = 11.8, D = 13.6). Haplotype genetic diversity increased over the course of CHB history, being lowest in Phase I, increasing in Phase II and was highest in Phase IV in all genotypes except genotype C. HBeAg loss by week 192 of tenofovir therapy was associated with different haplotype populations at baseline. CONCLUSION: Despite a previously unrecognised degree of HBV haplotype diversity and heterogeneity across the phases of CHB natural history, novel highly conserved sequences in key genes and regulatory regions were identified in multiple HBV genotypes that should be further investigated as targets for new antiviral therapies and predictors of treatment response.

4.
Death Stud ; : 1-9, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32820706

RESUMO

The current study explores the bereavement and coping of fans following the death of a personally significant popular musician. Nine participants completed individual interviews and the data were analyzed using Interpretative Phenomenological Analysis. Three superordinate themes were identified: a meaningful relationship, disenfranchisement of grief, and social recognition of grief. The findings highlight that the impact of a musician's death is deeply personal yet socially underrecognized. The loss of the parasocial relationship with the musician is comparable to losing a close social contact. Future research should investigate the roles of culture and social media in bereavement following a musician's death.

5.
Curr Opin Organ Transplant ; 25(4): 357-363, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618715

RESUMO

PURPOSE OF REVIEW: Organ transplant recipients have an increased incidence of Clostridium difficile disease and lower clinical response rates compared with the general population. Transplant specific treatment approaches are not defined. Therefore, a review of therapeutics in the transplant population is needed. RECENT FINDINGS: A literature review on the current therapies for C. difficile was performed focusing on the evidence in transplant recipients and immunosuppressed populations. SUMMARY: Transplant patients warrant an aggressive approach to treatment. The authors propose a suggested treatment paradigm for therapy.

6.
Curr Opin Organ Transplant ; 25(4): 351-356, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32618720

RESUMO

PURPOSE OF REVIEW: Donor-derived disease with Mycobacterium tuberculosis (MTB) is likely to become more common as donor pools expand due to increasing transplant volume coupled with patterns of migration and global mobility. Our article reviews the current literature and provides a rational approach for clinicians managing the scenario of a living donor who has epidemiologic risk factors for tuberculosis exposure. RECENT FINDINGS: Tuberculous bacilli, formerly thought to exist latently only in pulmonary granulomas, are now known reside dormant in nonpulmonary organs. Kidney and liver grafts are thus vectors for donor transmitted MTB disease. Donors with elevated risk for latent MTB disease can be identified with tuberculin skin testing or IFN-γ release assay screening in combination with a thorough history to identify risk factors for latent disease. SUMMARY: Living donors with an elevated risk for prior MTB exposure provide an opportunity to treat latent disease prior to organ procurement and reduce the risk of donor transmitted disease and secondary morbidity. Improved identification of these high-risk donors can reduce both the incidence of posttransplant MTB disease and the risk of allograft compromise associated with treatment of latent and active disease in posttransplant recipients.

7.
Pathog Dis ; 78(5)2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32592391

RESUMO

There is considerable literature on the threat of antibiotic resistance and its impact on morbidity. However, an under-studied consideration is how carriage of these antibiotic resistant bacteria persist in an individual. The duration that a person harbors a resistant organism is critical in guiding future antimicrobial therapy. Key unexplored questions are the rate of clearance of these organisms and what drives their persistence. This paper attempts to examine these questions and offers some initial answers as well as avenues for further study.

8.
Plant Mol Biol ; 103(4-5): 425-441, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32266646

RESUMO

KEY MESSAGE: Aggregation across multiple networks highlights robust co-expression interactions and improves the functional connectivity of grapevine gene co-expression networks. In recent years, the rapid accumulation of transcriptome datasets from diverse experimental conditions has enabled the widespread use of gene co-expression network (GCN) analysis in plants. In grapevine, GCN analysis has shown great promise for gene function prediction, however, measurable progress is currently lacking. Using accumulated microarray datasets from the grapevine whole-genome array (33 experiments, 1359 samples), we explored how meta-analysis through aggregation influences the functional connectivity (performance) of derived networks using guilt-by-association neighbor voting. Two annotation schemes, i.e. MapMan BIN and Pfam, at two sparsity thresholds, i.e. top 100 (stringent) and 300 (relaxed) ranked genes were evaluated. We observed that aggregating across multiple networks improves performance dramatically, with the aggregate outperforming the majority of functional terms across individual networks. Network sparsity and size (i.e. the number of samples and aggregates) were key factors influencing performance while the choice of annotation scheme had little. Systematic comparison with various state-of-the-art microarray and RNA-seq networks was also performed, however, none outperformed the aggregate microarray network despite having good predictive performance. Repeating these series of tests using a functional enrichment-based performance metric also showed remarkably consistent findings with guilt-by-association neighbor voting. To demonstrate its functionality, we explore the function and transcriptional regulation of grapevine EXPANSIN genes. We envisage that network aggregation will offer new and unique opportunities for gene function prediction in future grapevine functional genomics studies. To this end, we make the aggregate networks and associated metadata publicly available at VTC-Agg (https://sites.google.com/view/vtc-agg).


Assuntos
Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Genoma de Planta/genética , Fenótipo , Proteínas de Plantas/genética , Vitis/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Genes de Plantas/genética , Proteínas de Plantas/metabolismo , RNA-Seq , Transcriptoma
9.
Planta ; 251(3): 60, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32030477

RESUMO

MAIN CONCLUSION: The phosphorylation status of MYB75 at T-131 affects protein stability, flavonoid profiles, and patterns of gene expression. The Arabidopsis transcription factor Myeloblastosis protein 75 (MYB75, AT1G56650) is known to act as a positive transcriptional regulator of genes required for flavonoid and anthocyanin biosynthesis. MYB75 was also shown to negatively regulate lignin and other secondary cell wall biosynthetic genes (Bhargava et al. in Plant Physiol 154(3):1428-1438, 2010). While transcriptional regulation of MYB75 has been described in numerous publications, little is known about post-translational control of MYB75 protein function. In a recent publication, light-induced activation of a MAP kinase (MPK4, AT4G01370) in Arabidopsis was reported to lead to MYB75 phosphorylation at two canonical MPK target sites, threonines, T-126 and T-131. This double phosphorylation event positively influenced MYB75 protein stability (Li et al. in Plant Cell 28(11):2866-2883, 2016). We have examined this phenomenon through use of phosphomutant forms of MYB75 and found that MYB75 is phosphorylated primarily at T-131, and that the phosphorylation of MYB75 recombinant protein in vitro can be catalyzed by multiple MAP kinases, including MPK3 (AT3G45640), MPK6 (AT2G43790), MPK4 and MPK11 (AT1G01560). We also demonstrate that MYB75 can bind to a large number of Arabidopsis MPK's in vitro, suggesting it could be a target of multiple signalling pathways. The impact of MYB75 phosphorylation at T-131 on the function of this transcription factor, in terms of localization, stability, and protein-protein interactions with known binding partners was examined in transgenic lines expressing phosphomimic and phosphonull versions of MYB75, to capture the behaviour of permanently phosphorylated and unphosphorylated MYB75 protein, respectively. In addition, we describe how ectopic over-expression of different phosphovariant forms of MYB75 (MYB75WT, MYB75T131A, and MYB75T131E) affects flavonoid biochemical profiles and global changes of gene expression in the corresponding transgenic Arabidopsis plants.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Fatores de Transcrição/metabolismo , Antocianinas/biossíntese , Antocianinas/química , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Vias Biossintéticas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Genes de Plantas , Luz , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Plantas Geneticamente Modificadas , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/efeitos da radiação , Estabilidade Proteica/efeitos dos fármacos , Transporte Proteico , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo , Plântula/efeitos da radiação , Sacarose/farmacologia , Fatores de Transcrição/genética
10.
J Exp Bot ; 71(10): 3126-3141, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31985780

RESUMO

Drought events are a major challenge for many horticultural crops, including grapes, which are often cultivated in dry and warm climates. It is not understood how the cuticle contributes to the grape berry response to water deficit (WD); furthermore, the cuticular waxes and the related biosynthetic pathways are poorly characterized in this fruit. In this study, we identified candidate wax-related genes from the grapevine genome by phylogenetic and transcriptomic analyses. Developmental and stress response expression patterns of these candidates were characterized across pre-existing RNA sequencing data sets and confirmed a high responsiveness of the pathway to environmental stresses. We then characterized the developmental and WD-induced changes in berry cuticular wax composition, and quantified differences in berry transpiration. Cuticular aliphatic wax content was modulated during development and an increase was observed under WD, with wax esters being strongly up-regulated. These compositional changes were related to up-regulated candidate genes of the aliphatic wax biosynthetic pathway, including CER10, CER2, CER3, CER1, CER4, and WSD1. The effect of WD on berry transpiration was not significant. This study indicates that changes in cuticular wax amount and composition are part of the metabolic response of the grape berry to WD, but these changes do not reduce berry transpiration.

11.
Plant J ; 101(1): 37-56, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31469934

RESUMO

The cannabis leaf is iconic, but it is the flowers of cannabis that are consumed for the psychoactive and medicinal effects of their specialized metabolites. Cannabinoid metabolites, together with terpenes, are produced in glandular trichomes. Superficially, stalked and sessile trichomes in cannabis only differ in size and whether they have a stalk. The objectives of this study were: to define each trichome type using patterns of autofluorescence and secretory cell numbers, to test the hypothesis that stalked trichomes develop from sessile-like precursors, and to test whether metabolic specialization occurs in cannabis glandular trichomes. A two-photon microscopy technique using glandular trichome intrinsic autofluorescence was developed which demonstrated that stalked glandular trichomes possessed blue autofluorescence correlated with high cannabinoid levels. These stalked trichomes had 12-16 secretory disc cells and strongly monoterpene-dominant terpene profiles. In contrast, sessile trichomes on mature flowers and vegetative leaves possessed red-shifted autofluorescence, eight secretory disc cells and less monoterpene-dominant terpene profiles. Moreover, intrinsic autofluorescence patterns and disc cell numbers supported a developmental model where stalked trichomes develop from apparently sessile trichomes. Transcriptomes of isolated floral trichomes revealed strong expression of cannabinoid and terpene biosynthetic genes, as well as uncharacterized genes highly co-expressed with CBDA synthase. Identification and characterization of two previously unknown and highly expressed monoterpene synthases highlighted the metabolic specialization of stalked trichomes for monoterpene production. These unique properties and highly expressed genes of cannabis trichomes determine the medicinal, psychoactive and sensory properties of cannabis products.

12.
Clin Infect Dis ; 70(1): 180, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31069390
13.
Liver Int ; 39(11): 2066-2076, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31379058

RESUMO

BACKGROUND AND AIM: Functional cure is the major goal of chronic hepatitis B (CHB) therapy though few biomarkers predict this outcome. HBsAg epitope occupancy can be influenced by therapeutic and immune pressure. The aim of this study was to map the HBsAg epitope profiles during long-term nucleos(t)ide analogue therapy in patients with genotype A CHB, in the context of HBsAg loss (SL)/seroconversion. METHODS: We evaluated 25 genotype A CHB patients in the GS-US-174-0103 trial of HBeAg-positive CHB patients treated with tenofovir or adefovir for 4 years, 14 who achieved SL whilst 11 had no change. We epitope mapped the major domains of HBsAg to identify those patients with HBsAg clearance profile (CP) (loss of binding at both loops 1 and 2 epitopes of the 'a' determinant) vs non-clearance profile (no change in epitope recognition, or loss of epitope binding at one loop only), correlating this to on-treatment HBsAg responses. Complexed anti-HBs was also measured. RESULTS: Analysis of the HBsAg epitope profiles of the 25 patients at baseline identified no predictive correlation with SL. In contrast, analysis at week 48 and end of study (week 192) or prior to SL identified significant predictive associations between development of HBsAg CPs and outcome of functional cure. The detection of a CP also correlated with the development of an alanine aminotransferase flare and detection of anti-HBs complexed with HBsAg. CONCLUSION: The detection of HBsAg CPs by epitope mapping represents a novel viral biomarker, reflecting an emerging anti-HBs selection pressure prior to functional cure.

14.
Curr Opin Organ Transplant ; 24(4): 490-496, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31169529

RESUMO

PURPOSE OF REVIEW: Carbapenem-resistant enterobacteriaceae (CRE) are a critical healthcare threat. Infections caused by CRE disproportionately affect transplant patients. Retrospective case studies suggest that up to 10% of transplant recipients develop a CRE infection. The current literature is reviewed with a particular focus on transplant-specific implications. RECENT FINDINGS: There are specific risks inherent to transplant recipients that result in an elevated risk for CRE carriage and subsequent infection. Additionally, the manifestations of these infections are dependent on the specific transplant type. The optimal treatment of CRE infections in transplant recipients has not been defined. SUMMARY: A reduction in the regional community CRE burden can lead to a secondary reduction in their occurrence within vulnerable transplant populations. Therefore, core principles of antibiotic stewardship and infection control within all levels of the healthcare system remains the most effective strategy for addressing the current health crisis. Simultaneously, an integrated approach to risk stratification and an approach to treatment is postulated for management of CRE infection within the solid-organ transplant population.


Assuntos
Proteínas de Bactérias/efeitos adversos , Infecções por Enterobacteriaceae/complicações , Transplante de Órgãos/efeitos adversos , beta-Lactamases/efeitos adversos , Humanos , Transplante de Órgãos/métodos
15.
Plant J ; 99(5): 988-1002, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31063661

RESUMO

Cold stress is a major limiting factor in grape (Vitis) productivity. In this study, we characterized a cold-responsive ethylene response factor (ERF) transcription factor, VaERF092, from Amur grape (Vitis amurensis). VaERF092 expression was induced by both low temperatures and the ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC), but was suppressed by treatment with the ethylene inhibitor aminoethoxyvinylglycine (AVG) under cold conditions. Ectopic expression of VaERF092 in Arabidopsis thaliana enhanced cold tolerance. Co-expression network analysis of V. vinifera genes indicated that WRKY33 might be a downstream target of VaERF092. This hypothesis was supported by the fact that VaWRKY33 was expressed temporally after VaERF092 expression and could also be induced by cold and ACC, and inhibited by AVG. Yeast one-hybrid, transient ß-glucuronidase (GUS) and dual-luciferase reporter assays provided evidence for an interaction between VaERF092 and a GCC-box element in the VaWRKY33 promoter. In addition, heterologous overexpression of VaWRKY33 in A. thaliana resulted in enhanced cold tolerance. VaERF092- and VaWRKY33 overexpressing grape calli showed lower low-temperature exothermic values than the empty vector (EV) calli, indicating enhanced tolerance to cold. Together, these results indicated that VaERF092 regulates VaWRKY33 through binding to its promoter GCC-box, leading to enhanced cold stress tolerance.

16.
BMC Plant Biol ; 19(1): 69, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30744556

RESUMO

BACKGROUND: Grape leaves provide the biochemical substrates for berry development. Thus, understanding the regulation of grapevine leaf metabolism can aid in discerning processes fundamental to fruit development and berry quality. Here, the temporal alterations in leaf metabolism in Merlot grapevine grown under sufficient irrigation and water deficit were monitored from veraison until harvest. RESULTS: The vines mediated water stress gradually and involving multiple strategies: osmotic adjustment, transcript-metabolite alteration and leaf shedding. Initially stomatal conductance and leaf water potential showed a steep decrease together with the induction of stress related metabolism, e.g. up-regulation of proline and GABA metabolism and stress related sugars, and the down-regulation of developmental processes. Later, progressive soil drying was associated with an incremental contribution of Ca2+ and sucrose to the osmotic adjustment concomitant with the initiation of leaf shedding. Last, towards harvest under progressive stress conditions following leaf shedding, incremental changes in leaf water potential were measured, while the magnitude of perturbation in leaf metabolism lessened. CONCLUSIONS: The data present evidence that over time grapevine acclimation to water stress diversifies in temporal responses encompassing the alteration of central metabolism and gene expression, osmotic adjustments and reduction in leaf area. Together these processes mitigate leaf water stress and aid in maintaining the berry-ripening program.


Assuntos
Folhas de Planta/metabolismo , Vitis/metabolismo , Frutas/metabolismo , Osmose , Prolina/metabolismo , Água/metabolismo , Ácido gama-Aminobutírico/metabolismo
17.
Ann Bot ; 123(6): 1053-1066, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-30789664

RESUMO

BACKGROUND AND AIMS: The processes of gene duplication, followed by divergence and selection, probably underpin the evolution of floral volatiles crucial to plant-insect interactions. The Australian sexually deceptive Chiloglottis orchids use a class of 2,5-dialkylcyclohexan-1,3-dione volatiles or 'chiloglottones' to attract specific male wasp pollinators. Here, we explore the expression and evolution of fatty acid pathway genes implicated in chiloglottone biosynthesis. METHODS: Both Chiloglottis seminuda and C. trapeziformis produce chiloglottone 1, but only the phylogenetically distinct C. seminuda produces this volatile from both the labellum callus and glandular sepal tips. Transcriptome sequencing and tissue-specific contrasts of the active and non-active floral tissues was performed. The effects of the fatty acid synthase inhibitor cerulenin on chiloglottone production were tested. Patterns of selection and gene evolution were investigated for fatty acid pathway genes. KEY RESULTS: Tissue-specific differential expression of fatty acid pathway transcripts was evident between active and non-active floral tissues. Cerulenin significantly inhibits chiloglottone 1 production in the active tissues of C. seminuda. Phylogenetic analysis of plant ß-ketoacyl synthase I (KASI), a protein involved in fatty acid biosynthesis, revealed two distinct clades, one of which is unique to the Orchidaceae (KASI-2B). Selection analysis indicated a strong signal of positive selection at the split of KASI-2B followed by relaxed purifying selection in the Chiloglottis clade. CONCLUSIONS: By capitalizing on a phylogenetically distinct Chiloglottis from earlier studies, we show that the transcriptional and biochemical dynamics linked to chiloglottone biosynthesis in active tissues are conserved across Chiloglottis. A combination of tissue-specific expression and relaxed purifying selection operating at specific fatty acid pathway genes may hold the key to the evolution of chiloglottones.


Assuntos
3-Oxoacil-(Proteína de Transporte de Acila) Sintase , Orchidaceae , Animais , Austrália , Flores , Masculino , Filogenia , Polinização
18.
J Child Neurol ; : 883073818822361, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30642234

RESUMO

OBJECTIVE:: To determine if patterns of hypoxic-ischemic brain injury on magnetic resonance imaging (MRI) in term newborns predict subsequent childhood epilepsy. Methods: This retrospective cohort study includes term newborns with encephalopathy (n = 181) born between 2004-2012 and admitted to British Columbia Children's Hospital. MRI was performed between 3 and 5 days of age. The predominant patterns of hypoxic-ischemic injury were classified as Normal, Watershed, Basal Nuclei, Total, and Focal-Multifocal. Lesions in hippocampus, motor and occipital cortex were noted. RESULTS:: Of 181 newborns, 166 (92%) survived the neonatal period, and 132 (80%) had follow-up with a median duration of 61 months (IQR: 28-95). Twenty-three children (17%) developed epilepsy. A higher proportion with Watershed, Basal Nuclei, or Total patterns developed epilepsy ( P < .001). Injury to motor cortex, hippocampus, and occipital lobe ( P < .01) were independent risk factors for epilepsy. In the adjusting logistic model, Watershed (odds ratio = 16.0, 95% CI [1.3, 197.2], P = .03) and Basal Nuclei injury (odds ratio = 19.4, 95% CI [1.9, 196.3], P = .01) remained independent risk factors. Therapeutic hypothermia did not alter these associations. Severity of brain injury and recurrent neonatal seizures are other clinical risk factors. Significance: In term newborns with hypoxic-ischemic encephalopathy, the predominant pattern of Watershed and Basal Nuclei injury are valuable predictors for development of epilepsy in later childhood.

19.
J Hepatol ; 70(5): 839-846, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30654067

RESUMO

BACKGROUND & AIMS: Treatment programs for people who inject drugs (PWID), including prisoners, are important for achieving hepatitis C elimination targets. There are multiple barriers to treatment of hepatitis C in prisons, including access to specialist physicians, testing and antiviral therapy, short prison sentences, and frequent inter-prison transfer. We aimed to assess the effectiveness of a nurse-led model of care for the treatment of prisoners with hepatitis C. METHODS: A statewide program for assessment and management of hepatitis C was developed in Victoria, Australia to improve access to care for prisoners. This nurse-led model of care is supported by telemedicine to provide decentralized care within all prisons in the state. We prospectively evaluated the feasibility and efficacy of this nurse-led model of care for hepatitis C within the 14 adult prisons over a 13-month period. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) using per protocol analysis. RESULTS: There were 416 prisoners included in the analysis. The median age was 41 years, 90% were male, 50% had genotype 3 and 44% genotype 1 hepatitis C and 21% had cirrhosis. Injecting drug use was reported by 68% in the month prior to prison entry, 54% were receiving opioid substitution therapy, and 86% reported never previously engaging with specialist HCV care. Treatment duration was 8 weeks in 24%, 12 weeks in 59%, and 24 weeks in 17% of treatment courses. The SVR12 rate was 96% (301/313) per protocol. Inter-prison transfer occurred during 26% of treatment courses but was not associated with lower SVR12 rates. No treatment-related serious adverse events occurred. CONCLUSION: Hepatitis C treatment using a decentralized, nurse-led model of care is highly effective and can reach large numbers of prisoners. Large scale prison treatment programs should be considered to support hepatitis C elimination efforts. LAY SUMMARY: There is a high burden of hepatitis C infection among prisoners worldwide. Prisoners who continue to inject drugs are also at risk of developing new infections. For this reason, the prison setting provides an opportunity to treat those people at greatest risk of infection and to stop transmission to others. We developed a new method of providing hepatitis C treatment to prisoners, in which nurses rather than doctors assessed prisoners locally at each prison site. Treatment was safe and most prisoners were cured. Such programs will contribute greatly to achieving the World Health Organization's hepatitis C elimination goals.

20.
Clin Infect Dis ; 68(2): 338-342, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-29986022

RESUMO

The treatment of osteomyelitis in patients with stage IV sacral pressure ulcers is controversial. We conducted a systematic literature review and did not find evidence of benefit of antibacterial therapy in this setting without concomitant surgical debridement and wound coverage. Furthermore, many patients with chronically exposed bone do not have evidence of osteomyelitis when biopsied, and magnetic resonance imaging may not accurately distinguish osteomyelitis from bone remodeling. The goal of therapy should be local wound care and assessment for the potential of wound closure. If the wound can be closed and osteomyelitis is present on bone biopsy, appropriate antibiotic therapy is reasonable. We find no data to support antibiotic durations of >6 weeks in this setting, and some authors recommend 2 weeks of therapy if the osteomyelitis is limited to cortical bone. If the wound will not be closed, we find no clear evidence supporting a role for antibiotic therapy.


Assuntos
Antibacterianos/uso terapêutico , Osteomielite/tratamento farmacológico , Osteomielite/etiologia , Lesão por Pressão/complicações , Sacro/patologia , Idoso , Humanos , Masculino , Lesão por Pressão/patologia
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