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1.
Appl Environ Microbiol ; : e0102624, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248464

RESUMO

Interactions between plants and soil microbial communities that benefit plant growth and enhance nutrient acquisition are driven by the selective release of metabolites from plant roots, or root exudation. To investigate these plant-microbe interactions, we developed a photoaffinity probe based on sorgoleone (sorgoleone diazirine alkyne for photoaffinity labeling, SoDA-PAL), a hydrophobic secondary metabolite and allelochemical produced in Sorghum bicolor root exudates. We applied SoDA-PAL to the identification of sorgoleone-binding proteins in Acinetobacter pittii SO1, a potential plant growth-promoting microbe isolated from sorghum rhizosphere soil. Competitive photoaffinity labeling of A. pittii whole cell lysates with SoDA-PAL identified 137 statistically enriched proteins, including putative transporters, transcriptional regulators, and a subset of proteins with predicted enzymatic functions. We performed computational protein modeling and docking with sorgoleone to prioritize candidates for experimental validation and then confirmed binding of sorgoleone to four of these proteins in vitro: the α/ß fold hydrolase SrgB (OH685_09420), a fumarylacetoacetase (OH685_02300), a lysophospholipase (OH685_14215), and an unannotated hypothetical protein (OH685_18625). Our application of this specialized sorgoleone-based probe coupled with structural bioinformatics streamlines the identification of microbial proteins involved in metabolite recognition, metabolism, and toxicity, widening our understanding of the range of cellular pathways that can be affected by a plant secondary metabolite.IMPORTANCEHere, we demonstrate that a photoaffinity-based chemical probe modeled after sorgoleone, an important secondary metabolite released by sorghum roots, can be used to identify microbial proteins that directly interact with sorgoleone. We applied this probe to the sorghum-associated bacterium Acinetobacter pittii and showed that probe labeling is dose-dependent and sensitive to competition with purified sorgoleone. Coupling the probe with proteomics and computational analysis facilitated the identification of putative sorgoleone binders, including a protein implicated in a conserved pathway essential for sorgoleone catabolism. We anticipate that discoveries seeded by this workflow will expand our understanding of the molecular mechanisms by which specific metabolites in root exudates shape the sorghum rhizosphere microbiome.

2.
Genes Dev ; 30(4): 447-59, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26848045

RESUMO

CRISPR-Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM.


Assuntos
Proteínas de Bactérias/metabolismo , Sistemas CRISPR-Cas/fisiologia , Desoxirribonucleases/metabolismo , Inativação Gênica/fisiologia , Plasmídeos/genética , RNA/metabolismo , Proteínas de Bactérias/genética , Clivagem do DNA , Ativação Enzimática , Ligação Proteica , Pyrococcus furiosus/fisiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38372870

RESUMO

Depression and suicidality are prevalent in youth and are associated with a range of negative outcomes. The current study aimed to evaluate a measurement-based care (MBC) software (VitalSign6) tool to improve the screening and treatment of depression and suicidality in youth aged 8-17 years within a rural, underserved population. To assess for depression and suicidality, the Patient Health Questionnaire-2 was administered as an initial screen, and the Patient Health Questionnaire-9 Modified for Adolescents (PHQ-9-A) was administered if the initial screen was positive. Data were collected at medical clinics over one year, and descriptive statistics and t-tests or Wilcoxon-Mann-Whitney tests were conducted. A total of 1,984 youth were initially screened (mean age of 13 years; 51.6% female); 24.2% screened positive for depression, and 14.9% endorsed suicidality. Of those who screened positive, the mean PHQ-9-A score was 12.8; 66.9% had PHQ-9-A scores in the moderate to severe range, and 44.2% endorsed suicidality. Almost half of the youth who screened positive for depression had at least one follow-up assessment, and about one quarter achieved remission 4 months after initial screening. Adolescents (12-17 years) had higher PHQ-9-A scores, higher suicidality, and more follow-up assessments than younger youth (8-11 years). Younger youth had higher rates of remission. The widespread use of MBC was feasible in this setting. It is important to utilize MBC to identify and treat youth with depression and suicidality and to do so in younger populations to improve their trajectory over time; VitalSign6 is one tool to help achieve these goals.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38896285

RESUMO

There is a high prevalence of untreated depression in adults and youth observed at the population level in the United States, and many who would benefit from treatment do not receive it. One proposed effort to increase access to care is the use of measurement-based care (MBC; repeated use of symptom measures for screening and treatment guidance) by primary care physicians to treat non-complex cases of depression. MBC has been shown to improve patient outcomes compared to care as usual, but there are barriers that need to be addressed at the health system level for effective implementation to occur. Herein we provide an overview of MBC and detail benefits and barriers of MBC implementation. Relevant considerations and guidance for implementing MBC are presented, and a case example of a health system implementing MBC is included. Though issues of reimbursement, limited human and technological resources, and resistance to systemic change are barriers to implementing MBC, effective strategies exist to overcome these barriers. In addition to helping health systems align with changes to value-based care models, effective implementation of MBC can likely improve patient outcomes and result in net financial benefits.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38340213

RESUMO

Integration of measurement-based care (MBC) into clinical practice has shown promise in improving treatment outcomes for depression. Yet, without a gold standard measure of MBC, assessing fidelity to the MBC model across various clinical settings is difficult. A central goal of the Texas Youth Depression and Suicide Research Network (TX-YDSRN) was to characterize MBC across the state of Texas through the development of a standardized tool to assess the use of MBC strategies when assessing depression, anxiety, side effects, and treatment adherence. A chart review of clinical visits indicated standardized depression measures (71.2%) and anxiety measures (64%) were being utilized across sites. The use of standardized measures to assess medication adherence and side effects was limited to less than six percent for both, with the majority utilizing clinical interviews to assess adherence and side effects; yet medication was changed in nearly half. Rates of utilization of standardized measures for participants with multiple MBC forms were similar to those who only provided one form.

6.
J Pharmacol Exp Ther ; 377(3): 398-406, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33785525

RESUMO

3,4-Methylenedioxy-N-methylcathinone (methylone) is a new psychoactive substance with stimulant properties and potential for abuse. Despite its popularity, limited studies have examined relationships between brain concentrations of methylone, its metabolites, and pharmacodynamic effects. The goal of the present study was 2-fold: 1) to determine pharmacokinetics of methylone and its major metabolites-4-hydroxy-3-methoxy-N-methylcathinone (HMMC), 3,4-dihydroxy-N-methylcathinone (HHMC), and 3,4-methylenedioxycathinone (MDC)-in rat brain and plasma and 2) to relate brain pharmacokinetic parameters to pharmacodynamic effects including locomotor behavior and postmortem neurochemistry. Male Sprague-Dawley rats received subcutaneous methylone (6, 12, or 24 mg/kg) or saline vehicle (n = 16/dose), and subgroups were decapitated after 40 or 120 minutes. Plasma and prefrontal cortex were analyzed for concentrations of methylone and its metabolites by liquid chromatography-tandem mass spectrometry. Frontal cortex and dorsal striatum were analyzed for dopamine, 5-HT, and their metabolites by high-performance liquid chromatography-electrochemical detection. Brain and plasma concentrations of methylone and its metabolites rose with increasing methylone dose, but brain methylone and MDC concentrations were greater than dose-proportional. Brain-to-plasma ratios for methylone and MDC were ≥ 3 (range 3-12), whereas those for HHMC and HMMC were ≤ 0.2 (range 0.01-0.2). Locomotor activity score was positively correlated with brain methylone and MDC, whereas cortical 5-HT was negatively correlated with these analytes at 120 minutes. Our findings show that brain concentrations of methylone and MDC display nonlinear accumulation. Behavioral and neurochemical effects of systemically administered methylone are related to brain concentrations of methylone and MDC but not its hydroxylated metabolites, which do not effectively penetrate into the brain. SIGNIFICANCE STATEMENT: Behavioral and neurochemical effects of methylone are related to brain concentrations of methylone and its metabolite MDC but not its hydroxylated metabolites, 4-hydroxy-3-methoxy-N-methylcathinone and 3,4-dihydroxy-N-methylcathinone, which do not effectively penetrate into the brain. Methylone and MDC display nonlinear accumulation in the brain, which could cause untoward effects on serotonin neurons in vulnerable brain regions, including the frontal cortex.


Assuntos
Encéfalo , Animais , Dopamina , Ratos , Serotonina
7.
Metab Eng ; 67: 250-261, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34265401

RESUMO

Poly(ethylene terephthalate) (PET) is the most abundantly consumed synthetic polyester and accordingly a major source of plastic waste. The development of chemocatalytic approaches for PET depolymerization to monomers offers new options for open-loop upcycling of PET, which can leverage biological transformations to higher-value products. To that end, here we perform four sequential metabolic engineering efforts in Pseudomonas putida KT2440 to enable the conversion of PET glycolysis products via: (i) ethylene glycol utilization by constitutive expression of native genes, (ii) terephthalate (TPA) catabolism by expression of tphA2IIA3IIBIIA1II from Comamonas and tpaK from Rhodococcus jostii, (iii) bis(2-hydroxyethyl) terephthalate (BHET) hydrolysis to TPA by expression of PETase and MHETase from Ideonella sakaiensis, and (iv) BHET conversion to a performance-advantaged bioproduct, ß-ketoadipic acid (ßKA) by deletion of pcaIJ. Using this strain, we demonstrate production of 15.1 g/L ßKA from BHET at 76% molar yield in bioreactors and conversion of catalytically depolymerized PET to ßKA. Overall, this work highlights the potential of tandem catalytic deconstruction and biological conversion as a means to upcycle waste PET.


Assuntos
Polietilenotereftalatos , Pseudomonas putida , Adipatos , Burkholderiales , Etilenos , Hidrolases , Ácidos Ftálicos , Pseudomonas putida/genética , Rhodococcus
8.
Metab Eng ; 62: 62-71, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32828991

RESUMO

Valorization of all major lignocellulose components, including lignin, cellulose, and hemicellulose is critical for an economically viable bioeconomy. In most biochemical conversion approaches, the standard process separately upgrades sugar hydrolysates and lignin. Here, we present a new process concept based on an engineered microbe that could enable simultaneous upgrading of all lignocellulose streams, which has the ultimate potential to reduce capital cost and enable new metabolic engineering strategies. Pseudomonas putida is a robust microorganism capable of natively catabolizing aromatics, organic acids, and D-glucose. We engineered this strain to utilize D-xylose by tuning expression of a heterologous D-xylose transporter, catabolic genes xylAB, and pentose phosphate pathway (PPP) genes tal-tkt. We further engineered L-arabinose utilization via the PPP or an oxidative pathway. This resulted in a growth rate on xylose and arabinose of 0.32 h-1 and 0.38 h-1, respectively. Using the oxidative L-arabinose pathway with the PPP xylose pathway enabled D-glucose, D-xylose, and L-arabinose co-utilization in minimal medium using model compounds as well as real corn stover hydrolysate, with a maximum hydrolysate sugar consumption rate of 3.3 g/L/h. After modifying catabolite repression, our engineered P. putida simultaneously co-utilized five representative compounds from cellulose (D-glucose), hemicellulose (D-xylose, L-arabinose, and acetic acid), and lignin-related compounds (p-coumarate), demonstrating the feasibility of simultaneously upgrading total lignocellulosic biomass to value-added chemicals.


Assuntos
Pseudomonas putida , Xilose , Ácido Acético , Arabinose , Ácidos Cumáricos , Fermentação , Glucose , Lignina , Pseudomonas putida/genética , Zea mays
9.
Metab Eng ; 59: 64-75, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31931111

RESUMO

Pseudomonas putida KT2440 has received increasing attention as an important biocatalyst for the conversion of diverse carbon sources to multiple products, including the olefinic diacid, cis,cis-muconic acid (muconate). P. putida has been previously engineered to produce muconate from glucose; however, periplasmic oxidation of glucose causes substantial 2-ketogluconate accumulation, reducing product yield and selectivity. Deletion of the glucose dehydrogenase gene (gcd) prevents 2-ketogluconate accumulation, but dramatically slows growth and muconate production. In this work, we employed adaptive laboratory evolution to improve muconate production in strains incapable of producing 2-ketogluconate. Growth-based selection improved growth, but reduced muconate titer. A new muconate-responsive biosensor was therefore developed to enable muconate-based screening using fluorescence activated cell sorting. Sorted clones demonstrated both improved growth and muconate production. Mutations identified by whole genome resequencing of these isolates indicated that glucose metabolism may be dysregulated in strains lacking gcd. Using this information, we used targeted engineering to recapitulate improvements achieved by evolution. Deletion of the transcriptional repressor gene hexR improved strain growth and increased the muconate production rate, and the impact of this deletion was investigated using transcriptomics. The genes gntZ and gacS were also disrupted in several evolved clones, and deletion of these genes further improved strain growth and muconate production. Together, these targets provide a suite of modifications that improve glucose conversion to muconate by P. putida in the context of gcd deletion. Prior to this work, our engineered strain lacking gcd generated 7.0 g/L muconate at a productivity of 0.07 g/L/h and a 38% yield (mol/mol) in a fed-batch bioreactor. Here, the resulting strain with the deletion of hexR, gntZ, and gacS achieved 22.0 g/L at 0.21 g/L/h and a 35.6% yield (mol/mol) from glucose in similar conditions. These strategies enabled enhanced muconic acid production and may also improve production of other target molecules from glucose in P. putida.


Assuntos
Glucose/metabolismo , Engenharia Metabólica , Pseudomonas putida , Ácido Sórbico/análogos & derivados , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Ácido Sórbico/metabolismo
10.
Mol Cell ; 45(3): 292-302, 2012 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-22227116

RESUMO

Small RNAs target invaders for silencing in the CRISPR-Cas pathways that protect bacteria and archaea from viruses and plasmids. The CRISPR RNAs (crRNAs) contain sequence elements acquired from invaders that guide CRISPR-associated (Cas) proteins back to the complementary invading DNA or RNA. Here, we have analyzed essential features of the crRNAs associated with the Cas RAMP module (Cmr) effector complex, which cleaves targeted RNAs. We show that Cmr crRNAs contain an 8 nucleotide 5' sequence tag (also found on crRNAs associated with other CRISPR-Cas pathways) that is critical for crRNA function and can be used to engineer crRNAs that direct cleavage of novel targets. We also present data that indicate that the Cmr complex cleaves an endogenous complementary RNA in Pyrococcus furiosus, providing direct in vivo evidence of RNA targeting by the CRISPR-Cas system. Our findings indicate that the CRISPR RNA-Cmr protein pathway may be exploited to cleave RNAs of interest.


Assuntos
Sequências Repetidas Invertidas , Pyrococcus furiosus/genética , Clivagem do RNA , RNA Arqueal/isolamento & purificação , Proteínas Arqueais/isolamento & purificação , Sequência de Bases , Engenharia Genética , Loci Gênicos , Imunoprecipitação , Substâncias Macromoleculares/isolamento & purificação , Dados de Sequência Molecular , Pyrococcus furiosus/metabolismo , RNA Antissenso , Análise de Sequência de RNA
12.
BMC Genomics ; 19(1): 129, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426285

RESUMO

BACKGROUND: Infertility is a longstanding limitation in livestock production with important economic impact for the cattle industry. Female reproductive traits are polygenic and lowly heritable in nature, thus selection for fertility is challenging. Beef cattle operations leverage estrous synchronization in combination with artificial insemination (AI) to breed heifers and benefit from an early and uniform calving season. A couple of weeks following AI, heifers are exposed to bulls for an opportunity to become pregnant by natural breeding (NB), but they may also not become pregnant during this time period. Focusing on beef heifers, in their first breeding season, we hypothesized that: a- at the time of AI, the transcriptome of peripheral white blood cells (PWBC) differs between heifers that become pregnant to AI and heifers that become pregnant late in the breeding season by NB or do not become pregnant during the breeding season; and b- the ratio of transcript abundance between genes in PWBC classifies heifers according to pregnancy by AI, NB, or failure to become pregnant. RESULTS: We generated RNA-sequencing data from 23 heifers from two locations (A: six AI-pregnant and five NB-pregnant; and B: six AI-pregnant and six non-pregnant). After filtering out lowly expressed genes, we quantified transcript abundance for 12,538 genes. The comparison of gene expression levels between AI-pregnant and NB-pregnant heifers yielded 18 differentially expressed genes (DEGs) (ADAM20, ALDH5A1, ANG, BOLA-DQB, DMBT1, FCER1A, GSTM3, KIR3DL1, LOC107131247, LOC618633, LYZ, MNS1, P2RY12, PPP1R1B, SIGLEC14, TPPP, TTLL1, UGT8, eFDR≤0.02). The comparison of gene expression levels between AI-pregnant and non-pregnant heifers yielded six DEGs (ALAS2, CNKSR3, LOC522763, SAXO2, TAC3, TFF2, eFDR≤0.05). We calculated the ratio of expression levels between all gene pairs and assessed their potential to classify samples according to experimental groups. Considering all samples, relative expression from two gene pairs correctly classified 10 out of 12 AI-pregnant heifers (P = 0.0028) separately from the other 11 heifers (NB-pregnant, or non-pregnant). CONCLUSION: The transcriptome profile in PWBC, at the time of AI, is associated with the fertility potential of beef heifers. Transcript levels of specific genes may be further explored as potential classifiers, and thus selection tools, of heifer fertility.


Assuntos
Fertilidade/genética , Inseminação Artificial/veterinária , Leucócitos/metabolismo , Carne Vermelha/normas , Transcriptoma , Animais , Cruzamento , Bovinos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Masculino , Gravidez , Resultado da Gravidez/veterinária , Fatores de Tempo
13.
Cereb Cortex ; 27(12): 5463-5476, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27733540

RESUMO

Clinical descriptions of cocaine addiction include compulsive drug seeking and maladaptive decision-making despite substantial aversive consequences. Research suggests that this may result from altered orbitofrontal cortex (OFC) function and its participation in outcome-based behavior. Clinical and animal studies also implicate serotonin in the regulation of OFC function in addiction and other neuropsychiatric disorders. Here we test the hypothesis that exposure to cocaine, through self-administration (CSA) or yoked-administration (CYA), alters the regulation of OFC function by 5-HT. Using whole-cell electrophysiology in brain slices from naïve rats we find that 5-HT1A receptors generate hyperpolarizing outward currents in layer-V OFC pyramidal neurons, and that 5-HT2A receptors increase glutamate release onto these cells. Following extended withdrawal from CSA or CYA, this 5-HT regulation of OFC activity is largely lost. In-situ hybridization of 5-HT receptor transcripts reveals that 5-HT1A receptor mRNA is unaffected and 5-HT2A receptor mRNA is significantly elevated after CSA or CYA. These results demonstrate that 5-HT control of OFC neurons is disrupted for extended periods following cocaine exposure. We hypothesize that this dysregulation of 5-HT signaling leads to enduring disruptions of OFC network activity that this is involved in impaired decision-making associated with cocaine addiction.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/metabolismo , Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Serotonina/metabolismo , Animais , Transtornos Relacionados ao Uso de Cocaína/patologia , Ácido Glutâmico/metabolismo , Hibridização In Situ , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Técnicas de Patch-Clamp , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , RNA Mensageiro/metabolismo , Ratos Long-Evans , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Autoadministração , Técnicas de Cultura de Tecidos
15.
Nucleic Acids Res ; 43(21): 10353-63, 2015 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-26519471

RESUMO

CRISPR-Cas systems silence plasmids and viruses in prokaryotes. CRISPR-Cas effector complexes contain CRISPR RNAs (crRNAs) that include sequences captured from invaders and direct CRISPR-associated (Cas) proteins to destroy corresponding invader nucleic acids. Pyrococcus furiosus (Pfu) harbors three CRISPR-Cas immune systems: a Cst (Type I-G) system with an associated Cmr (Type III-B) module at one locus, and a partial Csa (Type I-A) module (lacking known invader sequence acquisition and crRNA processing genes) at another locus. The Pfu Cmr complex cleaves complementary target RNAs, and Csa systems have been shown to target DNA, while the mechanism by which Cst complexes silence invaders is unknown. In this study, we investigated the function of the Cst as well as Csa system in Pfu strains harboring a single CRISPR-Cas system. Plasmid transformation assays revealed that the Cst and Csa systems both function by DNA silencing and utilize similar flanking sequence information (PAMs) to identify invader DNA. Silencing by each system specifically requires its associated Cas3 nuclease. crRNAs from the 7 shared CRISPR loci in Pfu are processed for use by all 3 effector complexes, and Northern analysis revealed that individual effector complexes dictate the profile of mature crRNA species that is generated.


Assuntos
Sistemas CRISPR-Cas , Pyrococcus furiosus/genética , Proteínas Associadas a CRISPR/metabolismo , DNA/metabolismo , Desoxirribonucleases/metabolismo , Plasmídeos/genética , RNA Arqueal/metabolismo
16.
Psychiatry Clin Psychopharmacol ; 34(1): 82-93, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38883882

RESUMO

Cannabis use is increasingly common. There is a need for validated tools to meaningfully assess recreational, medical, and disordered cannabis use in both research and clinical contexts. Cannabis assessments were considered against pre-determined inclusion criteria within a comprehensive review. Measures were categorized as either (i) evaluating use frequency or quantity, (ii) measuring symptoms of disordered use and withdrawal, or (iii) assessing use motives, effects, and perceptions. The applications and validations for each assessment are summarized. Finally, recommendations for refining of existing measures or development of new measures are presented. The literature review resulted in 289 publications that were reviewed in detail, yielding 21 assessments that met inclusion criteria. The applications of these assessments are described here, in addition to the information about the validation studies of each assessment. Based on the complication of these tools, 5 areas of potential development are highlighted to guide future research, including (i) sensitivity to the mode of cannabis administration as well as sensitivity to (ii) potency of cannabis products alongside frequency and quantity, (iii) unit equivalence, (iv) aligning clinical measures consistently with cannabis use disorder (CUD) diagnostic criteria, and (v) creating measures specific to medical users, their motives for use, and their perceptions of therapeutic benefits or side effects. Clinicians and researchers can pragmatically benefit from this summary of validated measures of cannabis use, and future work could improve the study of and clinical care for cannabis use and CUD by pursuing one or more key areas of development described here.

17.
J Child Adolesc Psychopharmacol ; 34(2): 80-88, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38252552

RESUMO

Background: Similar outcomes and remission rates have been found for the treatment of depression in adults in primary and psychiatric care settings. However, comparatively little is known about how pediatric depression is managed across different settings. This study aims to address this gap by comparing depression treatment in pediatric and psychiatric settings. We hypothesized that pediatric care settings would be more likely to treat individuals with lower depression severity and would select pharmacotherapy less frequently as a treatment option. Methods: Patients (n = 3498) were screened for depression at a children's hospital from May 2017 to May 2022 as part of the VitalSign6 project, a web-based application for depression management. The two-item patient health questionnaire (PHQ) was used for screening, and the data set contains patient-reported measures and provider-reported diagnoses and treatment selections at each clinic visit. Patients with nine-item PHQ (PHQ-9) scores ≥10 at baseline were included in the analysis to compare diagnosis and treatment recommendations between pediatric and psychiatric settings. Results: Among the 1323 patients who screened positive for depression, those in psychiatric settings had higher PHQ-9 scores (15.9 ± 5.0 vs. 12.1 ± 5.5; p < 0.0001). Patients with PHQ-9 ≥ 10 in psychiatric settings were more likely to be diagnosed with major depressive disorder (60.6% vs. 24.7%, p < 0.0001) and receive pharmacotherapy (54.8% vs. 6.6%) than those in pediatric settings. Pediatric setting patients were more likely to receive nonpharmacological treatment alone (36.3% vs. 4.3%) or an outside referral (27.7% vs. 5.7%). Remission rates did not significantly differ between the two settings. Conclusions: Youth in psychiatric settings are more likely to screen positive for depression and to have greater depression severity than those in pediatric settings. Both settings provide treatment recommendations for moderate-to-severe depression, but treatment types vary substantially. Yet, remission rates remain similar. Further research is needed to understand the nuances of treatment differences and their implications.


Assuntos
Transtorno Depressivo Maior , Adulto , Humanos , Adolescente , Criança , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Depressão/diagnóstico , Depressão/tratamento farmacológico , Psicoterapia , Assistência Ambulatorial , Centros Médicos Acadêmicos
18.
ISME J ; 18(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38984785

RESUMO

The rhizosphere constitutes a dynamic interface between plant hosts and their associated microbial communities. Despite the acknowledged potential for enhancing plant fitness by manipulating the rhizosphere, the engineering of the rhizosphere microbiome through inoculation has posed significant challenges. These challenges are thought to arise from the competitive microbial ecosystem where introduced microbes must survive, and the absence of adaptation to the specific metabolic and environmental demands of the rhizosphere. Here, we engineered a synthetic rhizosphere community (SRC1) with the anticipation that it would exhibit a selective advantage in colonizing the host Sorghum bicolor, thereby potentially fostering its growth. SRC1 was assembled from bacterial isolates identified either for their potential role in community cohesion through network analysis or for their ability to benefit from host-specific exudate compounds. The growth performance of SRC1 was assessed in vitro on solid media, in planta under gnotobiotic laboratory conditions, and in the field. Our findings reveal that SRC1 cohesion is most robust when cultivated in the presence of the plant host under laboratory conditions, with lineages being lost from the community when grown either in vitro or in a native field setting. We establish that SRC1 effectively promotes the growth of both above- and below-ground plant phenotypes in both laboratory and native field contexts. Furthermore, in laboratory conditions, these growth enhancements correlate with the transcriptional dampening of lignin biosynthesis in the host. Collectively, these results underscore the potential utility of synthetic microbial communities for modulating crop performance in controlled and native environments alike.


Assuntos
Bactérias , Microbiota , Rizosfera , Microbiologia do Solo , Sorghum , Sorghum/microbiologia , Sorghum/crescimento & desenvolvimento , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/crescimento & desenvolvimento , Raízes de Plantas/microbiologia
19.
Sch Psychol ; 39(4): 377-386, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38976401

RESUMO

Rates of depression in youth are continuing to increase at a steady rate, yet these youth often do not receive mental health services (Bertha & Balázs, 2013; Thomas et al., 2011). Schools are an ideal setting to connect youth to mental health services; however, many barriers exist with respect to schools having adequate resources and access to the appropriate levels of services (Duong et al., 2021; Owens & Peltier, 2002). Schools may collaborate with local community providers with available resources to address these gaps. The current article describes the pilot of a school-based mental health promotion program intended to reduce depression in youth by promoting access to care through referrals to community providers. Data were collected, via self-report measures, every 3 months for 12 months from students from three middle and high schools in North Texas. The students (N = 88) enrolled in this program experienced significant reductions in their depression symptoms at the end of 12 months. This program highlights the importance of school-community partnerships to promote access to care to address mental health concerns. The results from our pilot study demonstrate the feasibility and the potential of school-based programs in improving the mental health of youth in schools through community partnership. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Depressão , Pobreza , Serviços de Saúde Mental Escolar , Estudantes , Humanos , Projetos Piloto , Adolescente , Masculino , Feminino , Depressão/terapia , Estudantes/psicologia , Instituições Acadêmicas , Texas , Acessibilidade aos Serviços de Saúde , Serviços de Saúde Escolar , Promoção da Saúde/métodos
20.
J Affect Disord ; 364: 146-156, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39134154

RESUMO

OBJECTIVE: The burden of major depressive disorder is compounded by a limited understanding of its risk factors, the limited efficacy of treatments, and the lack of precision approaches to guide treatment selection. The Texas Resilience Against Depression (T-RAD) study was designed to explore the etiology of depression by collecting comprehensive socio-demographic, clinical, behavioral, neurophysiological/neuroimaging, and biological data from depressed individuals (D2K) and youth at risk for depression (RAD). METHODS: This report details the baseline sociodemographic, clinical, and functional features from the initial cohort (D2K N = 1040, RAD N = 365). RESULTS: Of the total T-RAD sample, n = 1078 (76.73 %) attended ≥2 in-person visits, and n = 845 (60.14 %) attended ≥4 in-person visits. Most D2K (84.82 %) had a primary diagnosis of any depressive disorder, with a bipolar disorder diagnosis being prevalent (13.49 %). RAD participants (75.89 %) did not have a psychiatric diagnosis, but other non-depressive diagnoses were present. D2K participants had 9-item Patient Health Questionnaire scores at or near the moderate range (10.58 ± 6.42 > 24 yrs.; 9.73 ± 6.12 10-24 yrs). RAD participants were in the non-depressed range (2.19 ± 2.65). While the age ranges in D2K and RAD differ, the potential to conduct analyses that compare at-risk and depressed youth is a strength of the study. The opportunity to examine the trajectory of depressive symptoms in the D2K cohort over the lifespan is unique. LIMITATIONS: As a longitudinal study, missing data were common. CONCLUSION: T-RAD will allow data to be collected from multiple modalities on a clinically well-characterized sample. These data will drive important discoveries on diagnosis, treatment, and prevention of depression.


Assuntos
Transtorno Depressivo Maior , Humanos , Feminino , Masculino , Texas/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Adolescente , Estudos de Coortes , Adulto , Adulto Jovem , Resiliência Psicológica , Transtorno Bipolar/psicologia , Transtorno Bipolar/epidemiologia , Fatores de Risco , Criança
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