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1.
Bioinformatics ; 39(1)2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36440908

RESUMEN

MOTIVATION: The positional Burrows-Wheeler transform (PBWT) has led to tremendous strides in haplotype matching on biobank-scale data. For genetic genealogical search, PBWT-based methods have optimized the asymptotic runtime of finding long matches between a query haplotype and a predefined panel of haplotypes. However, to enable fast query searches, the full-sized panel and PBWT data structures must be kept in memory, preventing existing algorithms from scaling up to modern biobank panels consisting of millions of haplotypes. In this work, we propose a space-efficient variation of PBWT named Syllable-PBWT, which divides every haplotype into syllables, builds the PBWT positional prefix arrays on the compressed syllabic panel, and leverages the polynomial rolling hash function for positional substring comparison. With the Syllable-PBWT data structures, we then present a long match query algorithm named Syllable-Query. RESULTS: Compared to the most time- and space-efficient previously published solution to the long match query problem, Syllable-Query reduced the memory use by a factor of over 100 on both the UK Biobank genotype data and the 1000 Genomes Project sequence data. Surprisingly, the smaller size of our syllabic data structures allows for more efficient iteration and CPU cache usage, granting Syllable-Query even faster runtime than existing solutions. AVAILABILITY AND IMPLEMENTATION: https://github.com/ZhiGroup/Syllable-PBWT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Algoritmos , Genoma , Haplotipos , Genotipo , Programas Informáticos , Análisis de Secuencia de ADN/métodos
2.
Rheumatology (Oxford) ; 63(2): 414-422, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37184855

RESUMEN

OBJECTIVE: To study whether multimodal brain MRI comprising permeability and perfusion measures coupled with machine learning can predict neurocognitive function in young patients with SLE without neuropsychiatric manifestations. METHODS: SLE patients and healthy controls (HCs) (≤40 years of age) underwent multimodal structural brain MRI that comprised voxel-based morphometry (VBM), magnetization transfer ratio (MTR) and dynamic contrast-enhanced (DCE) MRI in this cross-sectional study. Neurocognitive function assessed by Automated Neuropsychological Assessment Metrics was reported as the total throughput score (TTS). Olfactory function was assessed. A machine learning-based model (i.e. glmnet) was constructed to predict TTS. RESULTS: Thirty SLE patients and 10 HCs were studied. Both groups had comparable VBM, MTR, olfactory bulb volume (OBV), olfactory function and TTS. While after correction for multiple comparisons the uncorrected increase in the blood-brain barrier (BBB) permeability parameters compared with HCs did not remain evident in SLE patients, DCE-MRI perfusion parameters, notably an increase in right amygdala perfusion, was positively correlated with TTS in SLE patients (r = 0.636, false discovery rate P < 0.05). A machine learning-trained multimodal MRI model comprising alterations of VBM, MTR, OBV and DCE-MRI parameters mainly in the limbic system regions predicted TTS in SLE patients (r = 0.644, P < 0.0005). CONCLUSION: Multimodal brain MRI demonstrated increased right amygdala perfusion that was associated with better neurocognitive performance in young SLE patients without statistically significant BBB leakage and microstructural abnormalities. A machine learning-constructed multimodal model comprising microstructural, perfusion and permeability parameters accurately predicted neurocognitive performance in SLE patients.


Asunto(s)
Encéfalo , Lupus Eritematoso Sistémico , Humanos , Estudios Transversales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Neuroimagen , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico por imagen , Lupus Eritematoso Sistémico/patología
3.
Headache ; 63(9): 1251-1258, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37740562

RESUMEN

BACKGROUND: Dihydroergotamine (DHE), like triptans, is contraindicated in patients with ischemic heart disease or coronary vasospasm. Its true safety, tolerability, and efficacy in patients with cardiovascular risk without ischemic heart disease or coronary vasospasm remain unclear. OBJECTIVES: To assess the safety, tolerability, and effectiveness of repetitive intravenous DHE in patients with cardiovascular risk factors. METHODS: A single-center, retrospective cohort study was conducted at the Jefferson Headache Center inpatient unit for refractory chronic migraine patients treated with our intravenous DHE protocol between January 1, 2019, and October 15, 2019. We evaluated tolerability and effectiveness outcomes based on atherosclerotic cardiovascular disease 10-year calculated risk scores, stratified into low (<5.0%) and elevated (≥5.0%) risk. Data were presented in mean ± standard deviation or median (25th percentile, 75th percentile) if non-normally distributed. RESULTS: Among 347 patients (median age of 46 [36, 57], female n = 278 [80.1%]), who received inpatient intravenous DHE, 227 patients (age 53 [45, 60], female 81.1%) had calculable risk scores, 64 (28.2%) had elevated risk, and 38 (16.7%) had cardiology consultations. There were no clinically significant electrocardiogram abnormalities or cardiovascular adverse events. The median hospital length of stay was 6 (5, 7) days. Compared to the low-risk group, those with elevated risk had higher nausea (31.3% vs. 14.1%, p = 0.008), but similar initial DHE dose (0.5 [0.25, 0.5] vs. 0.5 [0.25, 0.5], p = 0.009), lower final DHE dose (0.75 [0.5, 1] vs. 1 [0.75, 1] p < 0.001), and lower pain reduction after admission (-3.8 [2.1, 6] vs. -5 [3, 7] p = 0.037). CONCLUSION: Patients receiving intravenous DHE by the Jefferson Headache Center inpatient headache protocol had significantly reduced pain severity at discharge. No clinically significant cardiac or electrocardiogram abnormalities were detected in patients with elevated (or low) atherosclerotic cardiovascular disease risk. Repetitive intravenous DHE used by our protocol was safe in refractory chronic migraine patients.

4.
Neuromodulation ; 24(3): 507-511, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33016570

RESUMEN

OBJECTIVES: To report the explantation rates of high frequency 10 kHz spinal cord stimulation (SCS) in a real-world setting. MATERIALS AND METHODS: This is a retrospective review of patients implanted with high frequency spinal cord stimulators over a 4-year period in two outpatient private practice clinics, from July 2015 through June 2019, using the Kaplan-Meier product-limit method to estimate probabilities of implant survival over time. RESULTS: The estimated median time to explantation was 3.5 years (95% confidence interval [CI] = 3.1-3.7) [Correction added on 15 October 2020, after first online publication: The preceeding sentence was amended to reflect the estimated median time.]. The estimated probabilities of implant survival beyond 1, 2, and 3 years postimplantation were 88.4% (95% CI = 81.3-93.0%), 76.5% (95% CI = 67.8-83.2%), and 60.7% (95% CI = 50.2-69.6%), respectively. The minimum (i.e., known) cumulative percentages of patients explanted by 1, 2, and 3 years postimplantation were 11.1% (14/126), 22.2% (28/126), and 32.5% (41/126), respectively. 65.9% of patients in this study had prior neurostimulation. CONCLUSIONS: Recently, high frequency SCS technology has been demonstrated as more effective in treatment of lower- and leg-pain, compared to conventional low frequency SCS, in a 12-month randomized controlled trial (SENZA-RCT). Longer term results have yet to be published. In this study, we found that the explantation rate was much higher than expected, based on the prior studies demonstrating its efficacy. As the use of neuromodulation continues to grow, longitudinal data will be critical in understanding its long-term effects on treated patients.


Asunto(s)
Dolor Crónico , Estimulación de la Médula Espinal , Instituciones de Atención Ambulatoria , Dolor Crónico/terapia , Humanos , Manejo del Dolor , Estudios Retrospectivos , Médula Espinal , Resultado del Tratamiento
5.
Proc Natl Acad Sci U S A ; 113(16): 4368-73, 2016 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-27044072

RESUMEN

We report superresolution optical sectioning using a multiangle total internal reflection fluorescence (TIRF) microscope. TIRF images were constructed from several layers within a normal TIRF excitation zone by sequentially imaging and photobleaching the fluorescent molecules. The depth of the evanescent wave at different layers was altered by tuning the excitation light incident angle. The angle was tuned from the highest (the smallest TIRF depth) toward the critical angle (the largest TIRF depth) to preferentially photobleach fluorescence from the lower layers and allow straightforward observation of deeper structures without masking by the brighter signals closer to the coverglass. Reconstruction of the TIRF images enabled 3D imaging of biological samples with 20-nm axial resolution. Two-color imaging of epidermal growth factor (EGF) ligand and clathrin revealed the dynamics of EGF-activated clathrin-mediated endocytosis during internalization. Furthermore, Bayesian analysis of images collected during the photobleaching step of each plane enabled lateral superresolution (<100 nm) within each of the sections.


Asunto(s)
Clatrina/metabolismo , Endocitosis/fisiología , Factor de Crecimiento Epidérmico/metabolismo , Colorantes Fluorescentes/química , Imagenología Tridimensional , Fotoblanqueo , Línea Celular , Humanos , Microscopía Fluorescente/métodos
6.
J Med Internet Res ; 21(10): e13440, 2019 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-31625949

RESUMEN

BACKGROUND: Hospitalized older adults often experience isolation and disorientation while receiving care, placing them at risk for many inpatient complications, including loneliness, depression, delirium, and falls. Embodied conversational agents (ECAs) are technological entities that can interact with people through spoken conversation. Some ECAs are also relational agents, which build and maintain socioemotional relationships with people across multiple interactions. This study utilized a novel form of relational ECA, provided by Care Coach (care.coach, inc): an animated animal avatar on a tablet device, monitored and controlled by live health advocates. The ECA implemented algorithm-based clinical protocols for hospitalized older adults, such as reorienting patients to mitigate delirium risk, eliciting toileting needs to prevent falls, and engaging patients in social interaction to facilitate social engagement. Previous pilot studies of the Care Coach avatar have demonstrated the ECA's usability and efficacy in home-dwelling older adults. Further study among hospitalized older adults in a larger experimental trial is needed to demonstrate its effectiveness. OBJECTIVE: The aim of the study was to examine the effect of a human-in-the-loop, protocol-driven relational ECA on loneliness, depression, delirium, and falls among diverse hospitalized older adults. METHODS: This was a clinical trial of 95 adults over the age of 65 years, hospitalized at an inner-city community hospital. Intervention participants received an avatar for the duration of their hospital stay; participants on a control unit received a daily 15-min visit from a nursing student. Measures of loneliness (3-item University of California, Los Angeles Loneliness Scale), depression (15-item Geriatric Depression Scale), and delirium (confusion assessment method) were administered upon study enrollment and before discharge. RESULTS: Participants who received the avatar during hospitalization had lower frequency of delirium at discharge (P<.001), reported fewer symptoms of loneliness (P=.01), and experienced fewer falls than control participants. There were no significant differences in self-reported depressive symptoms. CONCLUSIONS: The study findings validate the use of human-in-the-loop, relational ECAs among diverse hospitalized older adults.


Asunto(s)
Hospitalización/tendencias , Telemedicina/métodos , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Comunicación , Femenino , Humanos , Relaciones Interpersonales , Masculino , Enfermeras y Enfermeros , Proyectos Piloto
7.
Am J Physiol Heart Circ Physiol ; 312(4): H711-H720, 2017 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-28188215

RESUMEN

Endothelial cystathionine γ-lyase (CSEγ) contributes to cardiovascular homeostasis, mainly through production of H2S. However, the molecular mechanisms that control CSEγ gene expression in the endothelium during cardiovascular diseases are unclear. The aim of the current study is to determine the role of specific histone deacetylases (HDACs) in the regulation of endothelial CSEγ. Reduced CSEγ mRNA expression and protein abundance were observed in human aortic endothelial cells (HAEC) exposed to oxidized LDL (OxLDL) and in aortas from atherogenic apolipoprotein E knockout (ApoE-/-) mice fed a high-fat diet compared with controls. Intact murine aortic rings exposed to OxLDL (50 µg/ml) for 24 h exhibited impaired endothelium-dependent vasorelaxation that was blocked by CSEγ overexpression or the H2S donor NaHS. CSEγ expression was upregulated by pan-HDAC inhibitors and by class II-specific HDAC inhibitors, but not by other class-specific inhibitors. The HDAC6 selective inhibitor tubacin and HDAC6-specific siRNA increased CSEγ expression and blocked OxLDL-mediated reductions in endothelial CSEγ expression and CSEγ promoter activity, indicating that HDAC6 is a specific regulator of CSEγ expression. Consistent with this finding, HDAC6 mRNA, protein expression, and activity were upregulated in OxLDL-exposed HAEC, but not in human aortic smooth muscle cells. HDAC6 protein levels in aortas from high-fat diet-fed ApoE-/- mice were comparable to those in controls, whereas HDAC6 activity was robustly upregulated. Together, our findings indicate that HDAC6 is upregulated by atherogenic stimuli via posttranslational modifications and is a critical regulator of CSEγ expression in vascular endothelium. Inhibition of HDAC6 activity may improve endothelial function and prevent or reverse the development of atherosclerosis.NEW & NOTEWORTHY Oxidative injury to endothelial cells by oxidized LDL reduced cystathionine γ-lyase (CSEγ) expression and H2S production, leading to endothelial dysfunction, which was prevented by histone deacetylase 6 (HDAC6) inhibition. Our data suggest HDAC6 as a novel therapeutic target to prevent the development of atherosclerosis.


Asunto(s)
Cistationina gamma-Liasa/metabolismo , Endotelio Vascular/enzimología , Endotelio Vascular/fisiología , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/genética , Animales , Apolipoproteínas E/genética , Cistationina gamma-Liasa/biosíntesis , Cistationina gamma-Liasa/genética , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Endotelio Vascular/efectos de los fármacos , Histona Desacetilasa 6 , Humanos , Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/farmacología , Lipoproteínas LDL/toxicidad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Contracción Miocárdica , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Vasodilatación/efectos de los fármacos , Vasodilatación/genética
8.
J Biol Chem ; 290(10): 6457-69, 2015 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-25586180

RESUMEN

The mechanism by which extracellular metabolites, including redox mediators and quorum-sensing signaling molecules, traffic through the extracellular matrix of biofilms is poorly explored. We hypothesize that functional amyloids, abundant in natural biofilms and possessing hydrophobic domains, retain these metabolites. Using surface plasmon resonance, we demonstrate that the quorum-sensing (QS) molecules, 2-heptyl-3-hydroxy-4(1H)-quinolone and N-(3-oxododecanoyl)-l-homoserine lactone, and the redox mediator pyocyanin bind with transient affinity to functional amyloids from Pseudomonas (Fap). Their high hydrophobicity predisposes them to signal-amyloid interactions, but specific interactions also play a role. Transient interactions allow for rapid association and dissociation kinetics, which make the QS molecules bioavailable and at the same time secure within the extracellular matrix as a consequence of serial bindings. Retention of the QS molecules was confirmed using Pseudomonas aeruginosa PAO1-based 2-heptyl-3-hydroxy-4(1H)-quinolone and N-(3-oxododecanoyl)-l-homoserine lactone reporter assays, showing that Fap fibrils pretreated with the QS molecules activate the reporters even after sequential washes. Pyocyanin retention was validated by electrochemical analysis of pyocyanin-pretreated Fap fibrils subjected to the same washing process. Results suggest that QS molecule-amyloid interactions are probably important in the turbulent environments commonly encountered in natural habitats.


Asunto(s)
Amiloide/química , Biopelículas , Pseudomonas aeruginosa/química , Percepción de Quorum/genética , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , Amiloide/metabolismo , Regulación Bacteriana de la Expresión Génica , Humanos , Pliegue de Proteína , Pseudomonas aeruginosa/genética
10.
Toxicol Pathol ; 43(6): 825-37, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26085543

RESUMEN

Glucokinase (GK) catalyzes the initial step in glycolysis and is a key regulator of glucose homeostasis. Therefore, glucokinase activators (GKa) have potential benefit in treating type 2 diabetes. Administration of a Bristol-Myers Squibb GKa (BMS-820132) to healthy euglycemic Sprague-Dawley (SD) rats and beagle dogs in 1 mo toxicology studies resulted in marked and extended hypoglycemia with associated clinical signs of toxicity and degenerative histopathological changes in the stomach, sciatic nerve, myocardium, and skeletal muscles at exposures comparable to those expected at therapeutic clinical exposures. To investigate whether these adverse effects were secondary to exaggerated pharmacology (prolonged hypoglycemia), BMS-820132 was administered daily to male Zucker diabetic fatty (ZDF) rats for 1 mo. ZDF rats are markedly hyperglycemic and insulin resistant. BMS-820132 did not induce hypoglycemia, clinical signs of hypoglycemia, or any of the histopathologic adverse effects observed in the 1 mo toxicology studies at exposures that exceeded those observed in SD rats and dogs. This indicates that the toxicity observed in euglycemic animals was secondary to the exaggerated pharmacology of potent GK activation. This study indicates that ZDF rats, with conventional toxicity studies, are a useful disease model for testing antidiabetic agents and determining toxicities that are independent of prolonged hypoglycemia.


Asunto(s)
Diabetes Mellitus/genética , Activadores de Enzimas/toxicidad , Hipoglucemia/inducido químicamente , Hipoglucemiantes/toxicidad , Ratas Zucker/metabolismo , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus/patología , Perros , Ingestión de Alimentos/efectos de los fármacos , Activadores de Enzimas/farmacocinética , Glucoquinasa/genética , Hipoglucemia/patología , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/farmacología , Insulina/sangre , Resistencia a la Insulina/genética , Masculino , Ratas , Especificidad de la Especie , Toxicocinética
11.
Biochim Biophys Acta ; 1828(8): 1723-30, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23562402

RESUMEN

The coupling between ATP hydrolysis and substrate transport remains a key question in the understanding of ABC-mediated transport. We show using the MalFGK2 complex reconstituted into nanodiscs, that membrane lipids participate directly to the coupling reaction by stabilizing the transporter in a low energy conformation. When surrounded by short acyl chain phospholipids, the transporter is unstable and hydrolyzes large amounts of ATP without inducing maltose. The presence of long acyl chain phospholipids stabilizes the conformational dynamics of the transporter, reduces its ATPase activity and restores dependence on maltose. Membrane lipids therefore play an essential allosteric function, they restrict the transporter ATPase activity to increase coupling to the substrate. In support to the notion, we show that increasing the conformational dynamics of MalFGK2 with mutations in MalF increases the transporter ATPase activity but decreases the maltose transport efficiency.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/química , Adenosina Trifosfatasas/metabolismo , Proteínas de Escherichia coli/química , Escherichia coli/metabolismo , Maltosa/metabolismo , Lípidos de la Membrana/metabolismo , Proteínas de Unión Periplasmáticas/química , Pliegue de Proteína , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Adenosina Trifosfato/metabolismo , Transporte Biológico , Dicroismo Circular , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Mutación/genética , Nanotecnología , Proteínas de Unión Periplasmáticas/genética , Proteínas de Unión Periplasmáticas/metabolismo
12.
Appl Microbiol Biotechnol ; 98(21): 9021-31, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25091046

RESUMEN

A stilbene-based membrane spanning conjugated oligoelectrolyte 4,4'-bis(4'-N,N-bis(6"-(N,N,N-trimethyl ammonium) hexyl) amino)-styryl) stilbene tetraiodide (DSSN+) has been reported to be able to interact with bacterial cells and enhance their bioelectricity generation in bioelectrochemical devices, although the mechanism remains elusive. The goal of this study was to elucidate the impacts of DSSN+ on extracellular bioactivity and the underlying mechanism. Specifically, extracellular ferrihydrite reduction by Shewanella oneidensis was used to evaluate the influence of cell-DSSN+ interaction. Our results show that DSSN+ enhanced ferrihydrite reduction by S. oneidensis in a growth-dependent manner. The incorporation of DSSN+ into S. oneidensis cell membrane increased the extracellular concentration of redox shuttles, i.e., flavins, and extracellular enzyme activities without significantly decreasing cell viability. The findings suggested that membrane permeabilization is the dominant mechanism for the enhancement of extracellular bioactivity in S. oneidensis by DSSN+. We further demonstrated that the interaction between DSSN+ and S. oneidensis cells enhanced biofilm formation and stability without compromising the overall biofilm activity. Taken together, our results suggest that membrane spanning conjugated oligoelectrolytes, of which DSSN+ is one of many possible molecular structures, may be applied to enhance extracellular bioactivity in bacteria toward more efficient biofilm-based biocatalysis.


Asunto(s)
Membrana Celular/efectos de los fármacos , Enzimas/metabolismo , Permeabilidad/efectos de los fármacos , Shewanella/efectos de los fármacos , Estilbenos/metabolismo , Supervivencia Celular/efectos de los fármacos , Compuestos Férricos/metabolismo , Oxidación-Reducción , Shewanella/crecimiento & desarrollo
13.
ScientificWorldJournal ; 2014: 139653, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25097866

RESUMEN

Microbial species have evolved diverse mechanisms for utilization of complex carbon sources. Proper combination of targeted species can affect bioenergy production from natural waste products. Here, we established a stable microbial consortium with Escherichia coli and Shewanella oneidensis in microbial fuel cells (MFCs) to produce bioenergy from an abundant natural energy source, in the form of the sarcocarp harvested from coconuts. This component is mostly discarded as waste. However, through its usage as a feedstock for MFCs to produce useful energy in this study, the sarcocarp can be utilized meaningfully. The monospecies S. oneidensis system was able to generate bioenergy in a short experimental time frame while the monospecies E. coli system generated significantly less bioenergy. A combination of E. coli and S. oneidensis in the ratio of 1:9 (v:v) significantly enhanced the experimental time frame and magnitude of bioenergy generation. The synergistic effect is suggested to arise from E. coli and S. oneidensis utilizing different nutrients as electron donors and effect of flavins secreted by S. oneidensis. Confocal images confirmed the presence of biofilms and point towards their importance in generating bioenergy in MFCs.


Asunto(s)
Fuentes de Energía Bioeléctrica/microbiología , Escherichia coli/crecimiento & desarrollo , Consorcios Microbianos , Shewanella/crecimiento & desarrollo , Escherichia coli/metabolismo , Microbiología Industrial/métodos , Shewanella/metabolismo
14.
Chem Sci ; 15(10): 3707-3710, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38455021

RESUMEN

N-heterocyclic carbenes, such as imidazole-2-ylidenes and imidazolin-2-ylidenes, the popular class of singlet carbenes introduced by Arduengo in 1991 have not been shown to be ambiphilic owing to the two σ-withdrawing, π-donating amino groups flanking the carbene centre. However, our experimental data suggest that ring-expanded N-heterocyclic carbenes (RE-NHCs), especially the seven and eight membered rings, are significantly ambiphilic. Our results also show that the steric environment in RE-NHCs can become a determining factor for controlling the E-H bond activation.

15.
Res Sq ; 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38746123

RESUMEN

Background Missouri is one of seven priority states identified by the Ending the HIV Epidemic Initiative, and St. Louis contains almost half of the people living with HIV (PLWH) in Missouri. As St. Louis has a marked history of structural racism and economic inequities, we utilized the Intersectionality Based Policy Analysis (IBPA) framework to guide a participatory needs assessment for planning and program development. Methods The planning team included researchers, the lead implementer from our community partner, and two community representatives, and had biweekly 60-90 minute meetings for 18 months. The planning team discussed and approved all research materials, reviewed and interpreted results, and made decisions about outreach, recruitment, conduct of the needs assessment and development of the planned intervention. The needs assessment integrated information from existing data, (1) interviews with (a) PLWH (n=12), (b) community leaders (n=5), (c) clinical leaders (n=4), and (d) community health workers (CHWs) (n=3) and (e) CHW supervisors (n=3) who participated in a Boston University-led demonstration project on CHWs in the context of HIV and (2) focus groups (2 FG, 12 participants) with front line health workers such as peer specialists, health coaches and outreach workers. A rapid qualitative analysis approach was used for all interviews and focus groups. Results The IBPA was used to guide team discussions of team values, definition and framing of the problem, questions and topics in the key informant interviews, and implementation strategies. Applying the IBPA framework contributed to a focus on intersectional drivers of inequities in HIV services. The effective management of HIV faces significant challenges from high provider turnover, insufficient integration of CHWs into care teams, and organizational limitations in tailoring treatment plans. Increasing use of CHWs for HIV treatment and prevention also faces challenges. People living with HIV (PLWH) encounter multiple barriers such as stigma, lack of social support, co-morbidities, medication side effects and difficulties in meeting basic needs. Conclusions Addressing intersectional drivers of health inequities may require multi-level, structural approaches. We see the IBPA as a valuable tool for participatory planning while integrating community engagement principles in program and implementation design for improving HIV outcomes.

16.
Pain Rep ; 9(3): e1160, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38646660

RESUMEN

Sustained widespread deployment of clinically and cost-effective models of integrated pain care could be bolstered by optimally aligning shared stakeholder values.

17.
Phys Chem Chem Phys ; 15(16): 5867-72, 2013 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-23487035

RESUMEN

It is important to tailor biotic-abiotic interfaces in order to maximize the utility of bioelectronic devices such as microbial fuel cells (MFCs), electrochemical sensors and bioelectrosynthetic systems. The efficiency of electron-equivalent extraction (or injection) across such biotic-abiotic interfaces is dependent on the choice of the microbe and the conductive electrode material. In this contribution, we show that spontaneous intercalation of a conjugated oligoelectrolyte, namely 4,4'-bis(4'-(N,N-bis(6''-(N,N,N-trimethylammonium)hexyl)amino)-styryl)stilbene tetraiodide (DSSN+), into the membranes of Escherichia coli leads to an increase in current generation in MFCs containing carbon-based electrodes. A combination of scanning electron microscopy (SEM) and confocal microscopy was employed to confirm the incorporation of DSSN+ into the cell membrane and biofilm formation atop carbon felt electrodes. Current collection was enhanced by more than 300% with addition of this conjugated oligoelectrolyte. The effect of DSSN+ concentration on electrical output was also investigated. Higher concentrations, up to 25 µM, lead to an overall increase in the number of charge equivalents transferred to the charge-collecting electrode, providing evidence in support of the central role of the synthetic system in improving device performance.


Asunto(s)
Carbono/química , Electrólitos/química , Escherichia coli/metabolismo , Compuestos de Amonio Cuaternario/química , Estilbenos/química , Fuentes de Energía Bioeléctrica , Membrana Celular/química , Membrana Celular/metabolismo , Electricidad , Electrodos , Microscopía Electrónica de Rastreo , Compuestos de Amonio Cuaternario/síntesis química , Estilbenos/síntesis química
18.
Pharmacogenomics ; 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37259972

RESUMEN

Aim: To assess knowledge, confidence and perceptions of healthcare professionals specializing in primary care and pain management at Brigham and Women's Hospital, related to clinical pharmacogenomics (PGx). Methods: A 25-question online survey was distributed to 328 Brigham and Women's Hospital clinicians for analysis. Results: Thirty-four clinicians completed the survey. Respondents had minimal experience with PGx and limited awareness of PGx resources. Although respondents expressed belief that PGx has utility to improve medication-related patient outcomes, many lack confidence to apply PGx results to their practice. For clinical drug-gene questions relevant to primary care and/or pain management, respondents scored poorly. Conclusion: More clinician education is needed for appropriate utilization of PGx in clinical practice as it pertains to primary care and pain management.

19.
Res Sq ; 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37398220

RESUMEN

The tumor microenvironment (TME) and the cellular interactions within it can be critical to tumor progression and treatment response. Although technologies to generate multiplex images of the TME are advancing, the many ways in which TME imaging data can be mined to elucidate cellular interactions are only beginning to be realized. Here, we present a novel approach for multipronged computational immune synapse analysis (CISA) that reveals T-cell synaptic interactions from multiplex images. CISA enables automated discovery and quantification of immune synapse interactions based on the localization of proteins on cell membranes. We first demonstrate the ability of CISA to detect T-cell:APC (antigen presenting cell) synaptic interactions in two independent human melanoma imaging mass cytometry (IMC) tissue microarray datasets. We then generate melanoma histocytometry whole slide images and verify that CISA can detect similar interactions across data modalities. Interestingly, CISA histoctyometry analysis also reveals that T-cell:macrophage synapse formation is associated with T-cell proliferation. We next show the generality of CISA by extending it to breast cancer IMC images, finding that CISA quantifications of T-cell:B-cell synapses are predictive of improved patient survival. Our work demonstrates the biological and clinical significance of spatially resolving cell-cell synaptic interactions in the TME and provides a robust method to do so across imaging modalities and cancer types.

20.
ACS Appl Mater Interfaces ; 15(21): 26128-26137, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37205770

RESUMEN

Selective and smooth dielectric-on-dielectric was achieved by water-free single-precursor chemical vapor deposition (CVD) processes with the help of aniline passivation. Aniline selective passivation was demonstrated on W surfaces in preference to SiO2 at 250, 300, and 330 °C. After aniline passivation, selective HfO2, Al2O3, and TiO2 were deposited only on the HF-cleaned SiO2 surface by water-free single-precursor CVD using hafnium tert-butoxide Hf(OtBu)4, aluminum-tri-sec-butoxide (ATSB), and titanium isopropoxide Ti(OiPr)4 as the precursor reactants, respectively. Hf(OtBu)4 and Ti(OiPr)4 single-precursor CVD was carried out at 300 °C, while the ATSB CVD process was conducted at 330 °C. HfO2 and Al2O3 nanoselectivity tests were performed on W/SiO2 patterned samples. Transmission electron microscopy images of the W/SiO2 patterned samples after deposition demonstrated nanoselectivity and low surface roughness of HfO2 and Al2O3 deposition on the SiO2 regions only.

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