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1.
Nature ; 595(7868): 532-536, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34290427

RESUMO

Nearly 50 years ago, Intel created the world's first commercially produced microprocessor-the 4004 (ref. 1), a modest 4-bit CPU (central processing unit) with 2,300 transistors fabricated using 10 µm process technology in silicon and capable only of simple arithmetic calculations. Since this ground-breaking achievement, there has been continuous technological development with increasing sophistication to the stage where state-of-the-art silicon 64-bit microprocessors now have 30 billion transistors (for example, the AWS Graviton2 (ref. 2) microprocessor, fabricated using 7 nm process technology). The microprocessor is now so embedded within our culture that it has become a meta-invention-that is, it is a tool that allows other inventions to be realized, most recently enabling the big data analysis needed for a COVID-19 vaccine to be developed in record time. Here we report a 32-bit Arm (a reduced instruction set computing (RISC) architecture) microprocessor developed with metal-oxide thin-film transistor technology on a flexible substrate (which we call the PlasticARM). Separate from the mainstream semiconductor industry, flexible electronics operate within a domain that seamlessly integrates with everyday objects through a combination of ultrathin form factor, conformability, extreme low cost and potential for mass-scale production. PlasticARM pioneers the embedding of billions of low-cost, ultrathin microprocessors into everyday objects.

2.
Med Teach ; : 1-4, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37883990

RESUMO

The United States faces an impending crisis in primary care physician shortages, while Physician Associates (PAs) and Nurse Practitioners (NPs) are poised to help bridge the gap. This manuscript explores a groundbreaking solution: introducing a clinical doctorate program tailored to PAs and NPs, designed to equip them with the knowledge and skills to assume leadership roles in primary care. Unlike traditional medical education, this innovative approach allows these professionals to continue their clinical practice while advancing their education, addressing the workforce shortage and the need for advanced leadership within the primary care landscape. This comprehensive curriculum includes intensive didactic coursework, residency-like training, credentialing examinations, and research opportunities, positioning PAs and NPs as critical contributors to the future of primary care. By recognizing their untapped potential and investing in their advanced education, we can elevate the quality and accessibility of primary care, ensuring that healthcare delivery reaches new heights.

3.
New Phytol ; 235(6): 2454-2465, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35708662

RESUMO

Fruit development has been central in the evolution and domestication of flowering plants. In common bean (Phaseolus vulgaris), the principal global grain legume staple, two main production categories are distinguished by fibre deposition in pods: dry beans, with fibrous, stringy pods; and stringless snap/green beans, with reduced fibre deposition, which frequently revert to the ancestral stringy state. Here, we identify genetic and developmental patterns associated with pod fibre deposition. Transcriptional, anatomical, epigenetic and genetic regulation of pod strings were explored through RNA-seq, RT-qPCR, fluorescence microscopy, bisulfite sequencing and whole-genome sequencing. Overexpression of the INDEHISCENT ('PvIND') orthologue was observed in stringless types compared with isogenic stringy lines, associated with overspecification of weak dehiscence-zone cells throughout the pod vascular sheath. No differences in DNA methylation were correlated with this phenotype. Nonstringy varieties showed a tandemly direct duplicated PvIND and a Ty1-copia retrotransposon inserted between the two repeats. These sequence features are lost during pod reversion and are predictive of pod phenotype in diverse materials, supporting their role in PvIND overexpression and reversible string phenotype. Our results give insight into reversible gain-of-function mutations and possible genetic solutions to the reversion problem, of considerable economic value for green bean production.


Assuntos
Phaseolus , Domesticação , Duplicação Gênica , Phaseolus/genética , Fenótipo , Retroelementos/genética
4.
Dysphagia ; 37(2): 260-265, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33638730

RESUMO

The goal of antibiotic stewardship is to improve antibiotic use, often by reducing unnecessary treatment. Bedside dysphagia screening tools help identify patients at high risk of aspiration following stroke. Presence of dysphagia does not indicate a need for antibiotic treatment. Therefore, this retrospective, cohort study was developed to evaluate the association of dysphagia and antibiotic prescribing following stroke. There were 117 patients included. Patients were placed into 2 cohorts based on the results of the dysphagia screening, with 55 patients positive for dysphagia and 62 patients negative for dysphagia. Patients with dysphagia tended to be older, had higher National Institutes of Health stroke scores, and lower renal function. Patients with dysphagia were prescribed more empiric antibiotics than those without dysphagia (18.2% vs. 3.2%, p = 0.01). This resulted in 53 antibiotic days of therapy in the dysphagia cohort compared to 19 antibiotic days of therapy in the no dysphagia cohort (p = 0.1). No patients later developed pneumonia and only one patient was started antibiotics after 48 h. Two cases of Clostridioides difficile were reported. Both patients were in the dysphagia cohort and received antibiotics. Multivariable logistic regression demonstrated that positive chest x-ray findings and failed dysphagia screen were independent conditions associated with initiating antibiotics. These findings indicate that antibiotic use was higher in patients following stroke with a positive dysphagia screen. Close monitoring of stroke patients, particularly when positive for dysphagia, might be an under-recognized antibiotic stewardship opportunity.


Assuntos
Gestão de Antimicrobianos , Transtornos de Deglutição , Acidente Vascular Cerebral , Estudos de Coortes , Transtornos de Deglutição/complicações , Transtornos de Deglutição/etiologia , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações
5.
Mol Psychiatry ; 25(8): 1749-1758, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-29942043

RESUMO

Addiction has been proposed as a 'reward deficient' state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.


Assuntos
Alcoolismo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dextroanfetamina/administração & dosagem , Dextroanfetamina/farmacologia , Peptídeos Opioides/metabolismo , Administração Oral , Adulto , Fentanila/administração & dosagem , Fentanila/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo
6.
Phytopathology ; 108(8): 1011-1018, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29648948

RESUMO

Recessive resistance to Bean common mosaic virus (BCMV) in common bean (Phaseolus vulgaris) is governed by four genes that include one strain-nonspecific helper gene bc-u, and three strain-specific genes bc-1, bc-2, and bc-3. The bc-3 gene was identified as an eIF4E translation initiation factor gene mediating resistance through disruption of the interaction between this protein and the VPg protein of the virus. The mode of action of bc-1 and bc-2 in expression of BCMV resistance is unknown, although bc-1 gene was found to affect systemic spread of a related potyvirus, Bean common mosaic necrosis virus. To investigate the possible role of both bc-1 and bc-2 genes in replication, cell-to-cell, and long-distance movement of BCMV in P. vulgaris, we tested virus spread of eight BCMV isolates representing pathogroups I, IV, VI, VII, and VIII in a set of bean differentials expressing different combinations of six resistance alleles including bc-u, bc-1, bc-12, bc-2, bc-22, and bc-3. All studied BCMV isolates were able to replicate and spread in inoculated leaves of bean cultivars harboring bc-u, bc-1, bc-12, bc-2, and bc-22 alleles and their combinations, while no BCMV replication was found in inoculated leaves of cultivar IVT7214 carrying the bc-u, bc-2, and bc-3 genes, except for isolate 1755a, which was capable of overcoming the resistance conferred by bc-2 and bc-3. In contrast, the systemic spread of all BCMV isolates from pathogroups I, IV, VI, VII, and VIII was impaired in common bean cultivars carrying bc-1, bc-12, bc-2, and bc-22 alleles. The data suggest that bc-1 and bc-2 recessive resistance genes have no effect on the replication and cell-to-cell movement of BCMV, but affect systemic spread of BCMV in common bean. The BCMV resistance conferred by bc-1 and bc-2 and affecting systemic spread was found only partially effective when these two genes were expressed singly. The efficiency of the restriction of the systemic spread of the virus was greatly enhanced when the alleles of bc-1 and bc-2 genes were combined together.


Assuntos
Phaseolus/genética , Phaseolus/virologia , Doenças das Plantas/virologia , Proteínas de Plantas/metabolismo , Potyvirus , Transporte Biológico , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas não Estruturais Virais
7.
Phytopathology ; 107(7): 893-900, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28475025

RESUMO

Bean common mosaic necrosis virus (BCMNV) isolates belong to two pathogroups (PG), PG-III and PG-VI, which are distinguished in common bean due to the inability of the PG-III isolates of BCMNV to overcome the two recessive resistance alleles bc-1 and bc-12. The biological and molecular basis of this distinction between PG-III and PG-VI isolates of BCMNV is not known. Here, three isolates of BCMNV were typed biologically on a set of 12 bean differentials and molecularly through whole-genome sequencing. Two isolates (1755b and TN1a) were assigned to PG-VI and one isolate (NL8-CA) was assigned to PG-III. Isolate NL8-CA (PG-III) induced only local necrosis on inoculated leaves in 'Top Crop' and 'Jubila' bean harboring the I gene and the bc-1 allele, whereas isolates TN1, TN1a, and 1755b (all PG-VI) induced rapid whole-plant necrosis (WPN) in Top Crop 7 to 14 days postinoculation, and severe systemic necrosis but not WPN in Jubila 3 to 5 weeks postinoculation. In 'Redland Greenleaf C' expressing bc-1 and 'Redland Greenleaf B' expressing bc-12 alleles, isolate NL8-CA was able to systemically infect only a small proportion of upper uninoculated leaves (less than 13 and 3%, respectively). The whole genomes of isolates 1755b, TN1a, and NL8-CA were sequenced and sequence analysis revealed that, despite the overall high nucleotide sequence identity between PG-III and PG-VI isolates (approximately 96%), two areas of the BCMNV genome in the P1/HC-Pro and HC-Pro/P3 cistrons appeared to be more divergent between these two pathotypes of BCMNV. The data suggest that the phenotypic differences among PG-III and PG-VI isolates of BCMNV in common bean cultivars from host resistance groups 2, 3, and 9 carrying bc-1 alleles were related to the impaired systemic movement of the PG-III isolates to the upper, uninoculated leaves, and also suggest a role of the recessive bc-1 gene in interfering with systemic spread of BCMNV.


Assuntos
Fabaceae/genética , Regulação da Expressão Gênica de Plantas/imunologia , Vírus do Mosaico/classificação , Doenças das Plantas/imunologia , Alelos , Fabaceae/imunologia , Fabaceae/virologia , Genoma de Planta , Vírus do Mosaico/imunologia , Doenças das Plantas/virologia
8.
Neuroimage ; 132: 1-7, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26876472

RESUMO

The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [(11)C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [(11)C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n=12) underwent an [(11)C]Ro15 4513 PET scan and compared with matched healthy controls (n=13). We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [(11)C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [(11)C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [(11)C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates.


Assuntos
Alcoolismo/metabolismo , Azidas/farmacocinética , Benzodiazepinas/farmacocinética , Encéfalo/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Receptores de GABA-A/metabolismo , Adulto , Marcadores de Afinidade/farmacocinética , Radioisótopos de Carbono , Hipocampo/metabolismo , Humanos , Masculino , Memória , Núcleo Accumbens/metabolismo , Tomografia por Emissão de Pósitrons
10.
J Pediatr Psychol ; 40(10): 1034-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26050244

RESUMO

OBJECTIVE: To present a model of translational research for behavioral science that communicates the role of behavioral research at each phase of translation. METHODS: A task force identified gaps in knowledge regarding behavioral translational research processes and made recommendations regarding advancement of knowledge. RESULTS: A comprehensive model of translational behavioral research was developed. This model represents T1, T2, and T3 research activities, as well as Phase 1, 2, 3, and 4 clinical trials. Clinical illustrations of translational processes are also offered as support for the model. CONCLUSIONS: Behavioral science has struggled with defining a translational research model that effectively articulates each stage of translation and complements biomedical research. Our model defines key activities at each phase of translation from basic discovery to dissemination/implementation. This should be a starting point for communicating the role of behavioral science in translational research and a catalyst for better integration of biomedical and behavioral research.


Assuntos
Ciências do Comportamento , Pesquisa Translacional Biomédica , Pesquisa Comportamental , Humanos
11.
Phytopathology ; 105(11): 1487-95, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26196181

RESUMO

Resistance against Bean common mosaic virus (BCMV) in Phaseolus vulgaris is governed by six recessive resistance alleles at four loci. One of these alleles, bc-3, is able to protect P. vulgaris against all BCMV strains and against other potyviruses; bc-3 was identified as the eIF4E allele carrying mutated eukaryotic translation initiation factor gene. Here, we characterized a novel BCMV isolate 1755a that was able to overcome bc-2 and bc-3 alleles in common bean. Thus, it displayed a novel pattern of interactions with resistance genes in P. vulgaris, and was assigned to a new pathogroup, PG-VIII. The IVT7214 cultivar supporting the replication of BCMV-1755a was found to have the intact homozygous bc-3 cleaved amplified polymorphic sequences marker and corresponding mutations in the eIF4E allele that confer resistance to BCMV isolates from all other pathogroups as well as to other potyviruses. The VPg protein of 1755a had seven amino acid substitutions relative to VPgs of other BCMV isolates unable to overcome bc-3. The 1755a genome was found to be a recombinant between NL1, US1 (both PG-I), and a yet unknown BCMV strain. Analysis of the recombination patterns in the genomes of NL1 and US1 (PG-I), NY15P (PG-V), US10 and RU1-OR (PG-VII), and 1755a (PG-VIII), indicated that P1/HC-Pro cistrons of BCMV strains may interact with most resistance genes. This is the first report of a BCMV isolate able to overcome the bc-3 resistance allele, suggesting that the virus has evolved mechanisms to overcome multiple resistance genes available in common bean.


Assuntos
Resistência à Doença/genética , Fator de Iniciação 4E em Eucariotos/genética , Genoma Viral , Phaseolus/imunologia , Potyvirus/patogenicidade , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos , Interações Hospedeiro-Patógeno , Dados de Sequência Molecular , Mutação , Phaseolus/genética , Phaseolus/virologia , Doenças das Plantas , Potyvirus/isolamento & purificação , Sorotipagem , Proteínas não Estruturais Virais/química
12.
13.
Synapse ; 68(8): 355-62, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24756906

RESUMO

Though GABA is the major inhibitory neurotransmitter in the brain, involved in a wide variety of brain functions and many neuropsychiatric disorders, its intracellular and metabolic presence provides uncertainty in the interpretation of the GABA signal measured by (1)H-MRS. Previous studies demonstrating the sensitivity of this technique to pharmacological manipulations of GABA have used nonspecific challenges that make it difficult to infer the exact source of the changes. In this study, the synaptic GABA reuptake inhibitor tiagabine, which selectively blocks GAT1, was used to test the sensitivity of J-difference edited (1)H-MRS to changes in extracellular GABA concentrations. MEGA-PRESS was used to obtain GABA-edited spectra in 10 male individuals, before and after a 15-mg oral dose of tiagabine. In the three voxels measured, no significant changes were found in GABA+ concentration after the challenge compared to baseline. This dose of tiagabine is known to modulate synaptic GABA and neurotransmission through studies using other imaging modalities, and significant increases in self-reported sleepiness scales were observed. Therefore, it is concluded that recompartmentalization of GABA through transport block does not have a significant impact on total GABA concentration. Furthermore, it is likely that the majority of the magnetic resonance spectroscopy (MRS)-derived GABA signal is intracellular. It should be considered, in individual interpretation of GABA MRS studies, whether it is appropriate to attribute observed effects to changes in neurotransmission.


Assuntos
Encéfalo/metabolismo , Inibidores da Captação de Neurotransmissores , Ácidos Nipecóticos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Sinapses/metabolismo , Ácido gama-Aminobutírico/metabolismo , Adulto , Encéfalo/efeitos dos fármacos , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Captação de Neurotransmissores/efeitos adversos , Ácidos Nipecóticos/efeitos adversos , Sinapses/efeitos dos fármacos , Tiagabina , Adulto Jovem
14.
Phytopathology ; 104(7): 786-93, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24915430

RESUMO

Bean common mosaic virus (BCMV) exists as a complex of strains classified by reactions to resistance genes found in common bean (Phaseolus vulgaris); seven BCMV pathotypes have been distinguished thus far, numbered I to VII. Virus genetic determinants involved in pathogenicity interactions with resistance genes have not yet been identified. Here, we describe the characterization of two novel field isolates of BCMV that helped to narrow down these genetic determinants interacting with specific P. vulgaris resistance factors. Based on a biological characterization on common bean differentials, both isolates were classified as belonging to pathotype VII, similar to control isolate US10, and both isolates exhibited the B serotype. The whole genome was sequenced for both isolates and found to be 98 to 99% identical to the BCMV isolate RU1 (pathotype VI), and a single name was retained: BCMV RU1-OR. To identify a genetic determinant of BCMV linked to the BCMV pathotype VII, the whole genome was also sequenced for two control isolates, US10 and RU1-P. Inspection of the nucleotide sequences for BCMV RU1-OR and US10 (both pathotype VII) and three closely related sequences of BCMV (RU1-P, RU1-D, and RU1-W, all pathotype VI) revealed that RU1-OR originated through a series of recombination events between US10 and an as-yet-unidentified BCMV parental genome, resulting in changes in virus pathology. The data obtained suggest that a fragment of the RU1-OR genome between positions 723 and 1,961 nucleotides that is common to US10 and RU1-OR in the P1-HC-Pro region of the BCMV genome may be responsible for the ability to overcome resistance in bean conferred by the bc-2(2) gene. This is the first report of a virus genetic determinant responsible for overcoming a specific BCMV resistance gene in common bean.


Assuntos
Anticorpos Antivirais/imunologia , Phaseolus/virologia , Doenças das Plantas/virologia , Potyvirus/genética , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA/genética , Ensaio de Imunoadsorção Enzimática , Dados de Sequência Molecular , Oregon , Potyvirus/imunologia , Potyvirus/isolamento & purificação , Potyvirus/patogenicidade , Recombinação Genética , Análise de Sequência de DNA , Washington
15.
Addict Biol ; 19(6): 1032-40, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23829344

RESUMO

The rewarding properties of some abused drugs are thought to reside in their ability to increase striatal dopamine levels. Similar increases have been shown in response to expectation of a positive drug effect. The actions of opioid drugs on striatal dopamine release are less well characterized. We examined whether heroin and the expectation of heroin reward increases striatal dopamine levels in human opioid addiction. Ten opioid-dependent participants maintained on either methadone or buprenorphine underwent [(11) C]raclopride positron emission tomography imaging. Opioid-dependent participants were scanned three times, receiving reward from 50-mg intravenous heroin (diamorphine; pharmaceutical heroin) during the first scan to generate expectation of the same reward at the second scan, during which they only received 0.1-mg intravenous heroin. There was no heroin injection during the third scan. Intravenous 50-mg heroin during the first scan induced pronounced effects leading to high levels of expectation at the second scan. There was no detectable increase in striatal dopamine levels to either heroin reward or expectation of reward. We believe this is the first human study to examine whether expectation of heroin reward increases striatal dopamine levels in opioid addiction. The absence of detectable increased dopamine levels to both the expectation and delivery of a heroin-related reward may have been due to the impact of substitute medication. It does however contrast with the changes seen in abstinent stimulant users, suggesting that striatal dopamine release alone may not play such a pivotal role in opioid-maintained individuals.


Assuntos
Antecipação Psicológica/fisiologia , Transtornos Relacionados ao Uso de Opioides/psicologia , Recompensa , Adulto , Idoso , Analgésicos Opioides/farmacologia , Buprenorfina/farmacologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Antagonistas de Dopamina , Humanos , Masculino , Metadona/farmacologia , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/diagnóstico por imagem , Transtornos Relacionados ao Uso de Opioides/reabilitação , Tomografia por Emissão de Pósitrons/métodos , Racloprida , Adulto Jovem
16.
Conn Med ; 78(9): 537-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25675594

RESUMO

Blastomycosis is a disease caused by the fungus Blastomyces dermatitidis. Pulmonary blastomycosis is the most common form of blastomycosis. Disseminated blastomycosis is the fulminant form of the disease, with rare reports of peritoneal cavity involvement. We report a case of extensive form of the disease presenting initially as abdominal pain and mimicking peritoneal carcinomatosis.


Assuntos
Blastomicose/complicações , Blastomicose/diagnóstico , Carcinoma/diagnóstico , Neoplasias Peritoneais/diagnóstico , Dor Abdominal/etiologia , Líquido Ascítico/microbiologia , Blastomyces/isolamento & purificação , Blastomicose/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Doenças Peritoneais/microbiologia , Vômito/etiologia
17.
Int Ophthalmol ; 34(4): 945-50, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24234425

RESUMO

There are two previous reports of Candida dubliniensis endophthalmitis in North America. Here, we report a third case of C. dubliniensis endogenous endophthalmitis in a 31-year-old male patient who complained of left-sided decreased visual acuity. He had an associated mitral and tricuspid valve endocarditis, in the setting of intravenous drug use. Blood and sputum cultures were positive for C. dubliniensis. Fundoscopic examination was consistent with a fungal endophthalmitis. He was treated with fluconazole followed by intravenous liposomal amphotericin B for 6 weeks. C. dubliniensis is an important but rare cause of endophthalmitis in intravenous drug abusers.


Assuntos
Candida/isolamento & purificação , Candidíase/microbiologia , Endoftalmite/microbiologia , Infecções Oculares Fúngicas/microbiologia , Adulto , Candida/classificação , Humanos , Masculino , Abuso de Substâncias por Via Intravenosa/complicações
18.
Neuroimage Rep ; 4(3): 100211, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39345862

RESUMO

Alcohol dependence (AD) and gambling disorder (GD) are common addiction disorders with significant physical and mental health consequences. AD and GD are associated with dysregulated responses to reward which could be due to a common mechanism of dysregulated endogenous opioid signalling. We explored associations between reward anticipation responses, using the Monetary Incentive Delay (MID) functional magnetic resonance imaging (fMRI) task, and mu-opioid receptor (MOR) availability and endogenous opioid release capacity using [11C]carfentanil positron emission tomography (PET), in 13 AD, 15 GD and 14 heathy control (HC) participants. We also examined differences in MID task reward anticipation responses between AD, GD and HC participants. These were secondary exploratory analysis of data collected to examine differences in MOR PET in addiction. We did not find significant differences in MID win > neutral anticipation BOLD responses compared between participant groups in a priori ROIs (ventral striatum, putamen, caudate) or whole brain analyses. We found no significant correlations between MID win > neutral anticipation BOLD responses and [11C]carfentanil PET measures, except for limited negative correlations between putamen MOR availability and MID win > neutral anticipation BOLD response in AD participants. Previous research has suggested a limited role of endogenous opioid signalling on MID task reward anticipation responses in AD and HCs as these responses are not modulated by opioid receptor blockade and this may explain our lack of significant correlations in HC and AD or GD participants. Our results, particularly the lack of differences in MID win > neutral anticipation BOLD responses across participants groups, may be limited due to only including AD or GD participants who are abstinent or in active treatment.

19.
Genes (Basel) ; 14(12)2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38137056

RESUMO

Color can be an indicator of plant health, quality, and productivity, and is useful to researchers to understand plant nutritional content in their studies. Color may be related to chlorophyll content and photosynthetic activity and provides information for those studying diseases and mineral nutrition because every nutrient deficiency and many diseases produce symptoms that affect color. In order to identify significant loci related to both leaf and pod color in a snap bean (Phaseolus vulgaris L.) diversity panel, a genome-wide association study (GWAS) was carried out. Leaf color in one and pod traits in multiple environments were characterized using a colorimeter. L*a*b* color data were recorded and used to calculate chroma (C*) and hue angle (H°). Leaves were evaluated at three positions (lower, middle, and upper) in the canopy and both pod exterior and interior colors were obtained. GWAS was conducted using two reference genomes that represent the Andean (G19833) and Middle American (5-593) domestication centers. Narrow sense heritabilities were calculated using the mixed linear model (MLM) method in genome association and prediction integrated tool (GAPIT), and significant single nucleotide polymorphisms (SNPs) for each color parameter were obtained using the Bayesian-information and linkage-disequilibrium iteratively nested keyway (BLINK) GWAS model with two principal components (PCAs). In comparison to pod color traits, narrow sense heritabilities of leaf traits were low and similar for both reference genomes. Generally, narrow sense heritability for all traits was highest in the lower, followed by middle, and then upper leaf positions. Heritability for both pod interior and exterior color traits was higher using the G19833 reference genome compared to 5-593 when evaluated by year and means across years. Forty-five significant SNPs associated with leaf traits and 872 associated with pods, totaling 917 significant SNPs were identified. Only one SNP was found in common for both leaf and pod traits on Pv03 in the 5-593 reference genome. One-hundred thirteen significant SNPs, 30 in leaves and 83 in pods had phenotypic variation explained (PVE) of 10% or greater. Fourteen SNPs (four from G19833 and ten from 5-593) with ≥10 PVE%, large SNP effect, and largest p-value for L* and H° pod exterior was identified on Pv01, Pv02, Pv03, and Pv08. More SNPs were associated with pod traits than with leaf traits. The pod interior did not exhibit colors produced by anthocyanins or flavonols which allowed the differentiation of potential candidate genes associated with chloroplast and photosynthetic activity compared to the pod exterior where candidate genes related to both flavonoids and photosynthesis affected color. Several SNPs were associated with known qualitative genes including the wax pod locus (y), persistent color (pc), purple pods (V), and two genes expressed in seeds but not previously reported to affect other plant tissues (B and J). An evaluation of significant SNPs within annotated genes found a number, within a 200 kb window, involved in both flavonoid and photosynthetic biosynthetic pathways.


Assuntos
Estudo de Associação Genômica Ampla , Phaseolus , Estados Unidos , Antocianinas , Teorema de Bayes , Phaseolus/genética , Folhas de Planta/genética
20.
Front Plant Sci ; 14: 1251919, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954997

RESUMO

Introduction: We now recognize that plant genotype affects the assembly of its microbiome, which in turn, affects essential plant functions. The production system for crop plants also influences the microbiome composition, and as a result, we would expect to find differences between conventional and organic production systems. Plant genotypes selected in an organic regime may host different microbiome assemblages than those selected in conventional environments. We aimed to address these questions using recombinant inbred populations of snap bean that differed in breeding history. Methods: Rhizosphere microbiomes of conventional and organic common beans (Phaseolus vulgaris L.) were characterized within a long-term organic research site. The fungal and bacterial communities were distinguished using pooled replications of 16S and ITS amplicon sequences, which originated from rhizosphere samples collected between flowering and pod set. Results: Bacterial communities significantly varied between organic and conventional breeding histories, while fungal communities varied between breeding histories and parentage. Within the organically-bred populations, a higher abundance of a plant-growth-promoting bacteria, Arthrobacter pokkalii, was identified. Conventionally-bred beans hosted a higher abundance of nitrogen-fixing bacteria that normally do not form functional nodules with common beans. Fungal communities in the organically derived beans included more arbuscular mycorrhizae, as well as several plant pathogens. Discussion: The results confirm that the breeding environment of crops can significantly alter the microbiome community composition of progeny. Characterizing changes in microbiome communities and the plant genes instrumental to these changes will provide essential information about how future breeding efforts may pursue microbiome manipulation.

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