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1.
BMC Genomics ; 25(1): 424, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684959

RESUMO

Salinity impacts crop growth and productivity and lowers the activities of rhizosphere microbiota. The identification and utilization of habitat-specific salinity-adapted plant growth-promoting rhizobacteria (PGPR) are considered alternative strategies to improve the growth and yields of crops in salinity-affected coastal agricultural fields. In this study, we characterize strain L1I39T, the first Aquabacter species with PGPR traits isolated from a salt-tolerant pokkali rice cultivated in brackish environments. L1I39T is positive for 1-aminocyclopropane-1-carboxylate deaminase activity and nitrogen fixation and can promote pokkali rice growth by supplying fixed nitrogen under a nitrogen-deficient seawater condition. Importantly, enhanced plant growth and efficient root colonization were evident in L1I39T-inoculated plants grown under 20% seawater but not in zero-seawater conditions, identifying brackish conditions as a key local environmental factor critical for L1I39T-pokkali rice symbiosis. Detailed physiological studies revealed that L1I39T is well-adapted to brackish environments. In-depth genome analysis of L1I39T identified multiple gene systems contributing to its plant-associated lifestyle and brackish adaptations. The 16S rRNA-based metagenomic study identified L1I39T as an important rare PGPR taxon. Based on the polyphasic taxonomy analysis, we established strain L1I39T as a novel Aquabacter species and proposed Aquabacter pokkalii sp nov. Overall, this study provides a better understanding of a marine-adapted PGPR strain L1I39T that may perform a substantial role in host growth and health in nitrogen-poor brackish environments.


Assuntos
Fixação de Nitrogênio , Oryza , Filogenia , Raízes de Plantas , Oryza/microbiologia , Oryza/genética , Oryza/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Rizosfera , Salinidade , Adaptação Fisiológica/genética , Simbiose , RNA Ribossômico 16S/genética
2.
Aust N Z J Psychiatry ; 58(4): 320-333, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37941354

RESUMO

OBJECTIVE: To determine antipsychotic utilisation patterns in Australian adults from 2005 to 2021, with a focus on on-label and off-label prescriptions. METHODS: We examined antipsychotic dispensing trends in adults from 2005 to 2021 using a 10% sample of the Pharmaceutical Benefits Scheme (PBS) dataset, which contains patient-level information on medicines dispensed throughout Australia. The lack of diagnostic information in PBS was substituted by analysing BEACH (Bettering the Evaluation And Care of Health) dataset, a cross-sectional national survey from 2000 to 2016, consisting of data from general practitioner-patient encounters. RESULTS: There were 5.6 million dispensings for 164,993 patients in PBS throughout this period; 69% patients had >1 dispensing, with a median of 6 per patient. Calculating the estimated period of exposure gave a total of 693,562 treatment episodes, with a median duration of 80 days. There were steady increases in both the incidence and prevalence of antipsychotic dispensings, mainly due to oral second-generation antipsychotics. The most commonly prescribed antipsychotics were quetiapine, olanzapine and risperidone, with a significant portion of patients receiving low-dose quetiapine without dose titration. Analysis of diagnostic indications from BEACH indicated that 27% of antipsychotic prescriptions were off-label for indications such as depression, dementia, anxiety and insomnia, at much lower prescribed daily dosages. CONCLUSION: The increasing prescribing and off-label use highlights concerns about chronic adverse effects caused by antipsychotics. The combined analysis of medication dispensings and the diagnostic indications for which they are prescribed is a novel approach and throws a spotlight on the need for additional monitoring of antipsychotics.


Assuntos
Antipsicóticos , Adulto , Humanos , Antipsicóticos/uso terapêutico , Fumarato de Quetiapina , Uso Off-Label , Estudos Retrospectivos , Estudos Transversais , Austrália/epidemiologia
3.
Mol Ther ; 30(12): 3619-3631, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-35965414

RESUMO

CRISPR technology has demonstrated broad utility for controlling target gene expression; however, there remains a need for strategies capable of modulating expression via the precise editing of non-coding regulatory elements. Here, we demonstrate that CRISPR base editors, a class of gene-modifying proteins capable of creating single-base substitutions in DNA, can be used to perturb gene expression via their targeted mutagenesis of cis-acting sequences. Using the promoter region of the human huntingtin (HTT) gene as an initial target, we show that editing of the binding site for the transcription factor NF-κB led to a marked reduction in HTT gene expression in base-edited cell populations. We found that these gene perturbations were persistent and specific, as a transcriptome-wide RNA analysis revealed minimal off-target effects resulting from the action of the base editor protein. We further demonstrate that this base-editing platform could influence gene expression in vivo as its delivery to a mouse model of Huntington's disease led to a potent decrease in HTT mRNA in striatal neurons. Finally, to illustrate the applicability of this concept, we target the amyloid precursor protein, showing that multiplex editing of its promoter region significantly perturbed its expression. These findings demonstrate the potential for base editors to regulate target gene expression.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes , Humanos , Animais , Camundongos
4.
Curr Pain Headache Rep ; 25(5): 34, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33760993

RESUMO

PURPOSE OF REVIEW: Prevalence of chronic low back pain (cLBP) is increasing. Sacroiliac joint (SIJ) is a common source of cLBP, but data behind its diagnosis and treatment is controversial. There is moderate quality evidence for effectiveness of therapeutic SIJ injections. However, there are no studies comparing the two most common steroid preparations, methylprednisolone (MTP) and triamcinolone (TAC) in SIJ injections. RECENT FINDINGS: After institutional IRB approval, a retrospective chart review was conducted to evaluate the effectiveness of SIJ injections in terms of pain relief at 1-month follow-up and compare MTP versus TAC. All injections were performed by a single pain physician with fluoroscopic guidance. RESULTS: Sixty-five percent of patients in the MTP group and 57% patients in the TAC group had >50% pain relief at 1-month follow-up, with no statistical difference between the two groups. Patients in the TAC group had significantly greater BMI and consisted of higher proportion of smokers (72% patients in TAC group versus 39% patients in the MTP group, p-value 0.004). Other sources of pain such as facet joints were unmasked post-procedurally after SIJ injections, with this unmasking being significant for the TAC group. Opiate use decreased in the MTP group from 35% pre-procedurally to 20% post-procedurally, and this difference did not reach statistical significance. Both MTP and TAC are effective in providing pain relief for SIJ pain at 1-month follow-up, with no statistical difference between the two types of steroids. Although not statistically significant, there is a modest reduction in opiate use in the MTP group.


Assuntos
Dor Crônica/tratamento farmacológico , Glucocorticoides/uso terapêutico , Dor Lombar/tratamento farmacológico , Metilprednisolona/uso terapêutico , Articulação Sacroilíaca , Triancinolona/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Mol Ther ; 26(1): 56-69, 2018 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-29175158

RESUMO

Oncolytic viruses (OV) are an emerging class of anticancer bio-therapeutics that induce antitumor immunity through selective replication in tumor cells. However, the efficacy of OVs as single agents remains limited. We introduce a strategy that boosts the therapeutic efficacy of OVs by combining their activity with immuno-modulating, small molecule protein tyrosine phosphatase inhibitors. We report that vanadium-based phosphatase inhibitors enhance OV infection in vitro and ex vivo, in resistant tumor cell lines. Furthermore, vanadium compounds increase antitumor efficacy in combination with OV in several syngeneic tumor models, leading to systemic and durable responses, even in models otherwise refractory to OV and drug alone. Mechanistically, this involves subverting the antiviral type I IFN response toward a death-inducing and pro-inflammatory type II IFN response, leading to improved OV spread, increased bystander killing of cancer cells, and enhanced antitumor immune stimulation. Overall, we showcase a new ability of vanadium compounds to simultaneously maximize viral oncolysis and systemic anticancer immunity, offering new avenues for the development of improved immunotherapy strategies.


Assuntos
Vetores Genéticos/genética , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Compostos de Vanádio/farmacologia , Animais , Biomarcadores , Quimiocina CXCL9/metabolismo , Terapia Combinada , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Terapia Genética/métodos , Humanos , Imunoterapia , Mediadores da Inflamação/metabolismo , Interferon Tipo I/metabolismo , Interferon gama/metabolismo , Ativação Linfocitária/imunologia , Camundongos , Mortalidade , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Nat Methods ; 12(11): 1077-84, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26414013

RESUMO

We report Single Molecule Cluster Analysis (SiMCAn), which utilizes hierarchical clustering of hidden Markov modeling-fitted single-molecule fluorescence resonance energy transfer (smFRET) trajectories to dissect the complex conformational dynamics of biomolecular machines. We used this method to study the conformational dynamics of a precursor mRNA during the splicing cycle as carried out by the spliceosome. By clustering common dynamic behaviors derived from selectively blocked splicing reactions, SiMCAn was able to identify the signature conformations and dynamic behaviors of multiple ATP-dependent intermediates. In addition, it identified an open conformation adopted late in splicing by a 3' splice-site mutant, invoking a mechanism for substrate proofreading. SiMCAn enables rapid interpretation of complex single-molecule behaviors and should prove useful for the comprehensive analysis of a plethora of dynamic cellular machines.


Assuntos
Análise por Conglomerados , Precursores de RNA/química , Splicing de RNA , Trifosfato de Adenosina/química , Domínio Catalítico , Simulação por Computador , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Humanos , Íntrons , Cadeias de Markov , Mutação , Conformação de Ácido Nucleico , Sítios de Splice de RNA , RNA Mensageiro/química , Spliceossomos/química
7.
Int J Syst Evol Microbiol ; 64(Pt 2): 545-550, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24126636

RESUMO

A Gram-stain-negative, strictly aerobic, slightly halophilic, non-motile and rod-shaped bacterial strain, designated P2E16(T), was isolated from mangrove (Avicennia marina) rhizosphere, collected at Devipattinam mangroves, Tamil Nadu, India. Strain P2E16(T) grew optimally at pH 7.0-8.0, at 25-28 °C and in the presence of 2-3% (w/v) NaCl. 16S rRNA gene analysis showed that strain P2E16(T) was phylogenetically closely related to the genus Zunongwangia, with Zunongwangia profunda SM-A87(T) as the closest related type strain (98.2% 16S rRNA gene sequence similarity) and less than 93% 16S rRNA gene sequence similarity to all other members of the family Flavobacteriaceae. Strain P2E16(T) contained MK-6 as the major respiratory quinone, phosphatidylethanolamine as the predominant polar lipid and iso-C(15 : 0) (17.8%), iso-C(17 : 0) 3-OH (15.1%), C(15 : 0) (12.8%), iso-C(17 : 1)ω9c (9.8%), iso-C(15 : 1) G (9.0%), and summed feature 3 (comprising C(16 : 1)ω7c and/or iso-C(15 : 0) 2-OH; 7.1%) as the major fatty acids. The DNA G+C content was 34.3 mol%. Differential phenotypic properties, together with the phylogenetic distinctiveness and low DNA-DNA relatedness demonstrated that strain P2E16(T) was distinct from the type strain of Zunongwangia profunda. On the basis of these presented data, strain P2E16(T) is considered to represent a novel species of the genus Zunongwangia, for which the name Zunongwangia mangrovi sp. nov. is proposed. The type strain is P2E16(T) ( = DSM 24499(T) = LMG 26237(T) = KCTC 23496(T)). An emended description of the genus Zunongwangia is also provided.


Assuntos
Avicennia/microbiologia , Flavobacteriaceae/classificação , Filogenia , Rizosfera , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/genética , Flavobacteriaceae/isolamento & purificação , Índia , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosfatidiletanolaminas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
8.
Nanoscale Adv ; 6(9): 2487-2498, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38694467

RESUMO

Comb copolymer analogues of poly(lactic acid)-polyethylene glycol block copolymers (PLA-b-PEG) offer potential to overcome the inherent chemistry and stability limitations of their linear block copolymer counterparts. Herein, we examine the differences between P(L)LA10K-b-PEG10K and linear-comb copolymer analogues thereof in which the linear PEG block is replaced by poly(oligo(ethylene glycol) methacrylate) (POEGMA) blocks with different side chain (comb) lengths but the same overall molecular weight. P(L)LA10K-b-POEGMA47510K and P(L)LA10K-b-POEGMA200010K block copolymers were synthesized via activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and fabricated into self-assembled nanoparticles using flash nanoprecipitation via confined impinging jet mixing. Linear-comb copolymer analogues based on PLA-b-POEGMA yielded smaller but still well-controlled nanoparticle sizes (88 ± 2 nm and 114 ± 1 nm respectively compared to 159 ± 2 nm for P(L)LA10K-b-PEG10K nanoparticles) that exhibited improved colloidal stability relative to linear copolymer-based nanoparticles over a 15 day incubation period while maintaining comparably high cytocompatibility, although the comb copolymer analogues had somewhat lower loading capacity for doxorubicin hydrochloride. Cell spheroid studies showed that the linear-comb copolymers promoted enhanced tumor transport and thus cell killing compared to conventional linear block copolymers. In vivo studies showed all NP types could passively accumulate within implanted CT26 tumors but with different accumulation profiles, with P(L)LA10K-b-POEGMA200010K NPs showing continuous accumulation throughout the full 24 h monitoring period whereas tumor accumulation of P(L)LA10K-b-POEGMA47510K NPs was significant only between 8 h and 24 h. Overall, the linear-comb copolymer analogues exhibited superior stability, biodistribution, spheroid penetration, and inherent tunability over linear NP counterparts.

9.
Indian J Otolaryngol Head Neck Surg ; 76(3): 2761-2764, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38883490

RESUMO

Nasopalatine duct cyst, which is also known as incisive canal cyst, is the most common developmental cyst of the maxilla. It arises from the proliferation of the remnants of the nasopalatine duct stimulated by trauma or infection. In this article, the authors report a rare case of an extensive nasopalatine duct cyst in a 57-year-old Male associated with non-vital tooth. Clinical examination revealed facial asymmetry associated with swelling that is painful and tender. Correlating clinical and radiological findings, a diagnosis of nasopalatine duct cyst was formed, and the histopathological examination confirmed the diagnosis of nasopalatine duct cyst. This case highlights the importance of knowing that nasopalatine duct cyst can be associated with non-vital teeth, challenging the assumption that they are exclusively associated with vital teeth. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04513-1.

10.
Clin Cancer Res ; 29(20): 4289-4305, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37561398

RESUMO

PURPOSE: T-cell exhaustion limits immunotherapy for the treatment of solid tumors. Although immune checkpoint blockade and adoptive T-cell therapy (ACT) can mediate tumor regression, their potency is often determined by tumor burden. Here, we identified tumor burden-related pathway changes that are conducive to T-cell exhaustion. We then determined whether microenvironmental reprogramming via epigenetic modulation could reverse T-cell exhaustion and improve immunotherapeutic responsiveness. EXPERIMENTAL DESIGN: We developed a murine syngeneic tumor model wherein an increased burden ablated therapeutic responsiveness to ACT, which corresponded with systemic induction of T-cell exhaustion. Transcriptome analysis of these large tumors allowed us to characterize changes to immunosuppressive pathway expression during class I histone deacetylase inhibitor MS-275 treatment. We then measured the therapeutic impact of MS-275 during ACT and assessed T-cell exhaustion by transcriptome/phenotypic analysis. RESULTS: ACT durably regressed small tumors but failed to control large tumors, which were associated with systemic T-cell exhaustion and ablation of T-cell responses. Large tumors were defined by an immunosuppressive pathway signature. MS-275 reversed this pathway signature and promoted durable regression of large tumors during ACT. Prototypical exhaustion marker Tim-3 was selectively upregulated in transferred T cells despite displaying a reduced exhaustion signature. Instead, we observed enhanced activation-dependent signaling correlating with enrichment of the IL2-STAT5 signaling axis. Activated CD8+ T-cell responses were predominantly skewed toward terminal effector cell-like CD44+ Tim-3hi TCF1- CD127- KLRG1+ differentiation. CONCLUSIONS: Tumor burden-induced pathway changes can be reversed through epigenetic reprogramming, enabling the conversion from T-cell exhaustion to effector lineage differentiation.

11.
Sci Adv ; 8(3): eabk2485, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35044815

RESUMO

Cas13 nucleases are a class of programmable RNA-targeting CRISPR effector proteins that are capable of silencing target gene expression in mammalian cells. Here, we demonstrate that RfxCas13d, a Cas13 ortholog with favorable characteristics to other family members, can be delivered to the mouse spinal cord and brain to silence neurodegeneration-associated genes. Intrathecally delivering an adeno-associated virus vector encoding an RfxCas13d variant programmed to target superoxide dismutase 1 (SOD1), a protein whose mutation can cause amyotrophic lateral sclerosis, reduced SOD1 mRNA and protein in the spinal cord by >50% and improved outcomes in a mouse model of the disorder. We further show that intrastriatally delivering an RfxCas13d variant programmed to target huntingtin (HTT), a protein whose mutation is causative for Huntington's disease, led to a ~50% reduction in HTT protein in the mouse brain. Our results establish RfxCas13d as a versatile platform for knocking down gene expression in the nervous system.


Assuntos
Esclerose Lateral Amiotrófica , Sistemas CRISPR-Cas , Esclerose Lateral Amiotrófica/genética , Animais , Inativação Gênica , Mamíferos , Camundongos , Medula Espinal , Superóxido Dismutase , Superóxido Dismutase-1/genética
12.
Angew Chem Int Ed Engl ; 48(23): 4134-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19222079

RESUMO

It's a trap! DNA polyhedra formed through molecular self-assembly may function as nanocapsules for the targeted delivery of encapsulated entities. This functional aspect was demonstrated for the most complex DNA-based platonic solid: During the stepwise amalgamation of discrete polyhedra to form icosahedra, gold nanoparticles (GNPs) were encapsulated from solution (see illustration and TEM image of icosahedral cages containing GNPs).


Assuntos
DNA/química , Ouro/química , Nanopartículas Metálicas/química , Nanocápsulas/química , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Transmissão , Nanocápsulas/ultraestrutura , Conformação de Ácido Nucleico
13.
J Med Imaging Radiat Oncol ; 63(2): 225-227, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30467976

RESUMO

We describe a rare case of middle lobe lung torsion in a patient with a tension hydrothorax secondary to multicentric Castleman disease. The case demonstrates the difficulty of diagnosing torsion prospectively, and the possible sequelae of delayed detection. Although imaging features can be confusing, an awareness of this condition and careful image interpretation by radiologists could facilitate early recognition and management of a torted lobe.


Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Pneumopatias/diagnóstico por imagem , Pneumotórax/diagnóstico por imagem , Anormalidade Torcional/diagnóstico por imagem , Adulto , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Pneumopatias/cirurgia , Pneumotórax/cirurgia , Radiografia Torácica , Tomografia Computadorizada por Raios X , Anormalidade Torcional/cirurgia , Ultrassonografia
14.
Mol Ther Oncolytics ; 14: 179-187, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31276026

RESUMO

Irreproducibility of preclinical findings could be a significant barrier to the "bench-to-bedside" development of oncolytic viruses (OVs). A contributing factor is the incomplete and non-transparent reporting of study methodology and design. Using the NIH Principles and Guidelines for Reporting Preclinical Research, a core set of seven recommendations, we evaluated the completeness of reporting of preclinical OV studies. We also developed an evidence map identifying the current trends in OV research. A systematic search of MEDLINE and Embase identified all relevant articles published over an 18 month period. We screened 1,554 articles, and 236 met our a priori-defined inclusion criteria. Adenovirus (43%) was the most commonly used viral platform. Frequently investigated cancers included colorectal (14%), skin (12%), and breast (11%). Xenograft implantation (61%) in mice (96%) was the most common animal model. The use of preclinical reporting guidelines was listed in 0.4% of articles. Biological and technical replicates were completely reported in 1% of studies, statistics in 49%, randomization in 1%, blinding in 2%, sample size estimation in 0%, and inclusion/exclusion criteria in 0%. Overall, completeness of reporting in the preclinical OV therapy literature is poor. This may hinder efforts to interpret, replicate, and ultimately translate promising preclinical OV findings.

15.
Syst Appl Microbiol ; 41(6): 570-580, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30139512

RESUMO

Three novel strains namely, L1E11T, L1E4 and 228 were isolated as part of an ongoing study on 1-aminocyclopropane-1-carboxylate (ACC) deaminase expressing rhizobacteria from crops cultivated in saline affected coastal agro-ecosystems of Kerala, India. The novel strains were positive for many properties that are beneficial to plant growth including ACC deaminase (ACCd) activity that ranged from 1.87±0.27 to 2.88±0.71µmol of α-ketobutyrate/hr/mg of total protein. Presence of other traits such as biofilm formation, siderophore production, phosphate solubilisation, utilisation of root derived compounds and ability to colonise host roots indicates its plant-associated life style. In complement, the genomic data reveals gene features for higher adaptation to plant-associated environments. In-planta assays showed that L1E11T can promote and protect pokkali rice plants from 200mM NaCl stress. Phylogenetic, chemotaxonomic, phenotypic and genomic characterisation indicates that the novel strains belong to a novel genus and species of the order Oceanospirillales for which the names Pokkaliibacter gen. nov., and Pokkaliibacter plantistimulans sp. nov., are proposed with L1E11T (=DSM 28732T=MCC 2992T) as the type strain. Further, on the basis of low 16S rRNA sequence similarity, phylogenetic divergence, source of isolation and few differences in the phenotypic properties against its nearest taxon, a new family Balneatrichaceae fam. nov., is proposed to accommodate the two genera Balneatrix and Pokkaliibacter gen.nov. with Balneatrix as the type genus. An emended description of the genus Balneatrix is also presented.


Assuntos
Aminoácido Oxirredutases/metabolismo , Produtos Agrícolas/microbiologia , Oceanospirillaceae/classificação , Filogenia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Ácidos Graxos/química , Índia , Oceanospirillaceae/enzimologia , Oceanospirillaceae/genética , Oceanospirillaceae/isolamento & purificação , Oryza/microbiologia , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Rizosfera , Salinidade , Análise de Sequência de DNA
16.
Appl Clin Inform ; 9(3): 714-724, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30208496

RESUMO

BACKGROUND: Outpatient providers often do not receive discharge summaries from acute care providers prior to follow-up visits. These outpatient providers may use the after-visit summaries (AVS) that are given to patients to obtain clinical information. It is unclear how effectively AVS support care coordination between clinicians. OBJECTIVES: Goals for this effort include: (1) developing usability heuristics that may be applied both for assessment and to guide generation of medical documents in general, (2) conducting a heuristic evaluation to assess the use of AVS for communication between clinicians, and (3) providing recommendations for generating AVS that effectively support both patient/caregiver use and care coordination. METHODS: We created a 17-item heuristic evaluation instrument for assessing usability of medical documents. Eight experts used the instrument to assess each of four simulated AVS. The simulations were created using examples from two hospitals and two pediatric patient cases developed by the National Institute of Standards and Technology. RESULTS: Experts identified 224 unique usability problems ranging in severity from mild to catastrophic. Content issues (e.g., missing medical history, marital status of a 2-year-old) were rated as most severe, but widespread formatting and structural problems (e.g., inconsistent indentation, fonts, and headings; confusing ordering of information) were so distracting that they significantly reduced readers' ability to efficiently use the documents. Overall, issues in the AVS from Hospital 2 were more severe than those in the AVS from Hospital 1. CONCLUSION: The new instrument allowed for quick, inexpensive evaluations of AVS. Usability issues such as unnecessary information, poor organization, missing information, and inconsistent formatting make it hard for patients, caregivers, and clinicians to use the AVS. The heuristics in the new instrument may be used as guidance to adapt electronic health record systems so that they generate more useful and usable medical documents.


Assuntos
Continuidade da Assistência ao Paciente , Registros Eletrônicos de Saúde , Heurística , Assistência Ambulatorial , Documentação , Humanos , Pacientes Ambulatoriais
17.
Sci Transl Med ; 10(425)2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29367345

RESUMO

Resistance to oncolytic virotherapy is frequently associated with failure of tumor cells to get infected by the virus. Dimethyl fumarate (DMF), a common treatment for psoriasis and multiple sclerosis, also has anticancer properties. We show that DMF and various fumaric and maleic acid esters (FMAEs) enhance viral infection of cancer cell lines as well as human tumor biopsies with several oncolytic viruses (OVs), improving therapeutic outcomes in resistant syngeneic and xenograft tumor models. This results in durable responses, even in models otherwise refractory to OV and drug monotherapies. The ability of DMF to enhance viral spread results from its ability to inhibit type I interferon (IFN) production and response, which is associated with its blockade of nuclear translocation of the transcription factor nuclear factor κB (NF-κB). This study demonstrates that unconventional application of U.S. Food and Drug Administration-approved drugs and biological agents can result in improved anticancer therapeutic outcomes.


Assuntos
Fumarato de Dimetilo/farmacologia , NF-kappa B/metabolismo , Terapia Viral Oncolítica , Vírus Oncolíticos/fisiologia , Animais , Linhagem Celular Tumoral , Citocinas/biossíntese , Ésteres/farmacologia , Fumaratos/farmacologia , Glutationa/metabolismo , Humanos , Interferon Tipo I/farmacologia , Maleatos/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Vírus Oncolíticos/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Res Microbiol ; 168(2): 113-121, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27639667

RESUMO

Pokkali rice varieties are known for their saline tolerance when specifically grown in coastal saline affected agri-fields of southern Kerala. These fields are prone to seawater intrusion. During characterization of phytobeneficial rhizobacteria from this pokkali rice, L3E4T was isolated. This strain showed some plant growth-promoting functions (production of indole acetic acid (IAA), acetoin, and siderophore), biofilm formation and capacity to use a wide range of plant-derived organic compounds. In planta assay under axenic conditions showed a positive effect of L3E4T on pokkali rice growth; importantly, it was able to attach and colonize pokkali rice roots in the presence of natural seawater, a key adaptation required for survival in pokkali rice fields. Phylogenetic analysis using 16S rRNA, recA, and gyrB gene sequences showed that strain L3E4T belongs to the genus Novosphingobium, with Novosphingobium capsulatum GIFU 11526T and Novosphingobium rhizosphaerae JM.1T being the nearest phylogenetic relatives. In addition, DNA-DNA hybridization analysis and phenotypic traits established that this strain belongs to a novel Novosphingobium species, for which we propose the name Novosphingobium pokkalii sp. nov. The type strain is represented by strain L3E4T (=MTCC 12357T = KCTC 42224T).


Assuntos
Produtos Agrícolas/microbiologia , Oryza/microbiologia , Rizosfera , Sphingomonadaceae/genética , Sphingomonadaceae/isolamento & purificação , Acetoína/metabolismo , Cultura Axênica , Técnicas de Tipagem Bacteriana , Biofilmes , DNA Girase/genética , DNA Bacteriano/genética , Ácidos Graxos/metabolismo , Ácidos Indolacéticos/metabolismo , Hibridização de Ácido Nucleico , Fosfolipídeos/metabolismo , Filogenia , RNA Ribossômico 16S , Recombinases Rec A/genética , Plantas Tolerantes a Sal/microbiologia , Água do Mar/microbiologia , Análise de Sequência de DNA , Sideróforos/biossíntese , Sphingomonadaceae/metabolismo
20.
PLoS One ; 11(3): e0150322, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26963092

RESUMO

A novel yellow colony-forming bacterium, strain P3B162T was isolated from the pokkali rice rhizosphere from Kerala, India, as part of a project study aimed at isolating plant growth beneficial rhizobacteria from saline tolerant pokkali rice and functionally evaluate their abilities to promote plant growth under saline conditions. The novel strain P3B162T possesses plant growth beneficial traits such as positive growth on 1-aminocyclopropane-1-carboxylic acid (ACC), production of indole acetic acid (IAA) and siderophore. In addition, it also showed important phenotypic characters such as ability to form biofilm and utilization of various components of plant root exudates (sugars, amino acids and organic acids), clearly indicating its lifestyle as a plant rhizosphere associated bacterium. Taxonomically, the novel strain P3B162T was affiliated to the genus Arthrobacter based on the collective results of phenotypic, genotypic and chemotaxonomic analyses. Moreover, molecular analysis using 16S rRNA gene showed Arthrobacter globiformis NBRC 12137T, Arthrobacter pascens DSM 20545T and Arthrobacter liuii DSXY973T as the closely related phylogenetic neighbours, showing more than 98% 16S rRNA similarity values, whereas the recA gene analysis displayed Arthrobacter liuii JCM 19864T as the nearest neighbour with 94.7% sequence similarity and only 91.7% to Arthrobacter globiformis LMG 3813T and 88.7% to Arthrobacter pascens LMG 16255T. However, the DNA-DNA hybridization values between strain P3B162T, Arthrobacter globiformis LMG 3813T, Arthrobacter pascens LMG 16255T and Arthrobacter liuii JCM 19864T was below 50%. In addition, the novel strain P3B162T can be distinguished from its closely related type strains by several phenotypic characters such as colony pigment, tolerance to NaCl, motility, reduction of nitrate, hydrolysis of DNA, acid from sucrose, cell wall sugars and cell wall peptidoglycan structure. In conclusion, the combined results of this study support the classification of strain P3B162T as a novel Arthrobacter species and we propose Arthrobacter pokkalii sp.nov.as its name. The type strain is P3B162T (= KCTC 29498T = MTCC 12358T).


Assuntos
Arthrobacter , Oryza/microbiologia , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Rizosfera , Microbiologia do Solo , Arthrobacter/classificação , Arthrobacter/genética , Arthrobacter/isolamento & purificação , Índia
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